{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:16:33Z","timestamp":1785870993172,"version":"3.56.0"},"reference-count":64,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T00:00:00Z","timestamp":1755993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["GINOP-2.3.2-15-2016-00005"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00005"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["TK2016-78"],"award-info":[{"award-number":["TK2016-78"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["TKCS-2021\/32"],"award-info":[{"award-number":["TKCS-2021\/32"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["135784"],"award-info":[{"award-number":["135784"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["RRF-2.3.1-21-2022-00006"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00006"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["BO\/00513\/23\/5"],"award-info":[{"award-number":["BO\/00513\/23\/5"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["GINOP-2.3.2-15-2016-00005"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00005"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["TK2016-78"],"award-info":[{"award-number":["TK2016-78"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["TKCS-2021\/32"],"award-info":[{"award-number":["TKCS-2021\/32"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["135784"],"award-info":[{"award-number":["135784"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["RRF-2.3.1-21-2022-00006"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00006"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["BO\/00513\/23\/5"],"award-info":[{"award-number":["BO\/00513\/23\/5"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hungarian Research Network\u2014HUN-REN","award":["GINOP-2.3.2-15-2016-00005"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00005"]}]},{"name":"Hungarian Research Network\u2014HUN-REN","award":["TK2016-78"],"award-info":[{"award-number":["TK2016-78"]}]},{"name":"Hungarian Research Network\u2014HUN-REN","award":["TKCS-2021\/32"],"award-info":[{"award-number":["TKCS-2021\/32"]}]},{"name":"Hungarian Research Network\u2014HUN-REN","award":["135784"],"award-info":[{"award-number":["135784"]}]},{"name":"Hungarian Research Network\u2014HUN-REN","award":["RRF-2.3.1-21-2022-00006"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00006"]}]},{"name":"Hungarian Research Network\u2014HUN-REN","award":["BO\/00513\/23\/5"],"award-info":[{"award-number":["BO\/00513\/23\/5"]}]},{"name":"National Research, Development, and Innovation Fund of Hungary","award":["GINOP-2.3.2-15-2016-00005"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00005"]}]},{"name":"National Research, Development, and Innovation Fund of Hungary","award":["TK2016-78"],"award-info":[{"award-number":["TK2016-78"]}]},{"name":"National Research, Development, and Innovation Fund of Hungary","award":["TKCS-2021\/32"],"award-info":[{"award-number":["TKCS-2021\/32"]}]},{"name":"National Research, Development, and Innovation Fund of Hungary","award":["135784"],"award-info":[{"award-number":["135784"]}]},{"name":"National Research, Development, and Innovation Fund of Hungary","award":["RRF-2.3.1-21-2022-00006"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00006"]}]},{"name":"National Research, Development, and Innovation Fund of Hungary","award":["BO\/00513\/23\/5"],"award-info":[{"award-number":["BO\/00513\/23\/5"]}]},{"name":"National Laboratory for Health Security Hungary","award":["GINOP-2.3.2-15-2016-00005"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00005"]}]},{"name":"National Laboratory for Health Security Hungary","award":["TK2016-78"],"award-info":[{"award-number":["TK2016-78"]}]},{"name":"National Laboratory for Health Security Hungary","award":["TKCS-2021\/32"],"award-info":[{"award-number":["TKCS-2021\/32"]}]},{"name":"National Laboratory for Health Security Hungary","award":["135784"],"award-info":[{"award-number":["135784"]}]},{"name":"National Laboratory for Health Security Hungary","award":["RRF-2.3.1-21-2022-00006"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00006"]}]},{"name":"National Laboratory for Health Security Hungary","award":["BO\/00513\/23\/5"],"award-info":[{"award-number":["BO\/00513\/23\/5"]}]},{"name":"Hungarian Academy of Sciences","award":["GINOP-2.3.2-15-2016-00005"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00005"]}]},{"name":"Hungarian Academy of Sciences","award":["TK2016-78"],"award-info":[{"award-number":["TK2016-78"]}]},{"name":"Hungarian Academy of Sciences","award":["TKCS-2021\/32"],"award-info":[{"award-number":["TKCS-2021\/32"]}]},{"name":"Hungarian Academy of Sciences","award":["135784"],"award-info":[{"award-number":["135784"]}]},{"name":"Hungarian Academy of Sciences","award":["RRF-2.3.1-21-2022-00006"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00006"]}]},{"name":"Hungarian Academy of Sciences","award":["BO\/00513\/23\/5"],"award-info":[{"award-number":["BO\/00513\/23\/5"]}]},{"name":"EK\u00d6P-24-4 University Research Scholarship Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund","award":["GINOP-2.3.2-15-2016-00005"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00005"]}]},{"name":"EK\u00d6P-24-4 University Research Scholarship Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund","award":["TK2016-78"],"award-info":[{"award-number":["TK2016-78"]}]},{"name":"EK\u00d6P-24-4 University Research Scholarship Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund","award":["TKCS-2021\/32"],"award-info":[{"award-number":["TKCS-2021\/32"]}]},{"name":"EK\u00d6P-24-4 University Research Scholarship Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund","award":["135784"],"award-info":[{"award-number":["135784"]}]},{"name":"EK\u00d6P-24-4 University Research Scholarship Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund","award":["RRF-2.3.1-21-2022-00006"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00006"]}]},{"name":"EK\u00d6P-24-4 University Research Scholarship Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund","award":["BO\/00513\/23\/5"],"award-info":[{"award-number":["BO\/00513\/23\/5"]}]},{"name":"Tempus Public Foundation and the Hungarian Government","award":["GINOP-2.3.2-15-2016-00005"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00005"]}]},{"name":"Tempus Public Foundation and the Hungarian Government","award":["TK2016-78"],"award-info":[{"award-number":["TK2016-78"]}]},{"name":"Tempus Public Foundation and the Hungarian Government","award":["TKCS-2021\/32"],"award-info":[{"award-number":["TKCS-2021\/32"]}]},{"name":"Tempus Public Foundation and the Hungarian Government","award":["135784"],"award-info":[{"award-number":["135784"]}]},{"name":"Tempus Public Foundation and the Hungarian Government","award":["RRF-2.3.1-21-2022-00006"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00006"]}]},{"name":"Tempus Public Foundation and the Hungarian Government","award":["BO\/00513\/23\/5"],"award-info":[{"award-number":["BO\/00513\/23\/5"]}]},{"name":"University of Debrecen","award":["GINOP-2.3.2-15-2016-00005"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00005"]}]},{"name":"University of Debrecen","award":["TK2016-78"],"award-info":[{"award-number":["TK2016-78"]}]},{"name":"University of Debrecen","award":["TKCS-2021\/32"],"award-info":[{"award-number":["TKCS-2021\/32"]}]},{"name":"University of Debrecen","award":["135784"],"award-info":[{"award-number":["135784"]}]},{"name":"University of Debrecen","award":["RRF-2.3.1-21-2022-00006"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00006"]}]},{"name":"University of Debrecen","award":["BO\/00513\/23\/5"],"award-info":[{"award-number":["BO\/00513\/23\/5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: As part of the human adaptation to dairy consumption, the presence of the rs4988235-T variant in the MCM6 gene primarily determines lactase persistence in adult European populations, increasing the expression of the lactase-encoding LCT gene. Carriers of the C\/C variant are lactose intolerant, while carriers of the T\/T or T\/C variant have persistent lactase enzyme activity and are able to digest lactose in adulthood. While the association between lactose intolerance and increased cardiovascular risk (CVR) is well-known, the underlying causes have only been partly explored. The present study aimed to investigate the association of rs4988235 polymorphism with significant lipids affecting cardiovascular health and estimated CVR. Methods: The rs4988235 polymorphism was genotyped in 397 subjects from the general Hungarian population and 368 individuals from the Roma population. To characterize the overall lipid profile, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), apolipoprotein AI (ApoAI), and apolipoprotein B100 (ApoB100) levels were measured, and their ratios (TG\/HDL-C, LDL-C\/HDL-C, and ApoB100\/ApoAI) were calculated. Cardiovascular risk was estimated using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCE), Revised Pooled Cohort Equations (RPCE), and the Systematic Coronary Risk Evaluations (SCORE and SCORE2) algorithms. Adjusted linear and logistic regression analyses were performed, with p &lt; 0.05 considered significant. Results: The Roma population had a significantly higher prevalence of the C\/C genotype than the general population (65.5% vs. 40.3%, respectively). The results of the adjusted linear regression analysis showed a significant association between the C\/C genotype and higher LDL-C level (B = 0.126, p = 0.047) and ApoB100 level (B = 0.046, p = 0.013), as well as a higher LDL-C\/HDL-C ratio (B = 0.174, p = 0.021) and a higher ApoB100\/ApoAI ratio (B = 0.045, p = 0.002), as well as a lower HDL-C level (B = \u22120.041, p = 0.049). The C\/C genotype was also significantly associated with an increased cardiovascular risk (CVR) as estimated by the SCORE (B = 0.235, p = 0.034), SCORE2 (B = 0.414, p = 0.009), PCE (B = 0.536, p = 0.008), and RPCE (B = 0.289, p = 0.045) but not the FRS. After adjusting the statistical model further for ApoAI and ApoB100 levels, the significant correlation with the risk estimation algorithms disappeared (SCORE: p = 0.099; SCORE2: p = 0.283; PCE: p = 0.255; and RPCE: p = 0.370). Conclusions: Our results suggest that the C\/C genotype of rs4988235 is associated with significantly higher ApoB100 and lower ApoAI levels and consequently higher ApoB100\/ApoAI ratios, potentially contributing to an increased risk of cardiovascular disease. The results of the statistical analyses suggest that the association between lactose intolerant genotype and cardiovascular risk may be mediated indirectly via modification of the apolipoprotein profile.<\/jats:p>","DOI":"10.3390\/nu17172741","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:09:32Z","timestamp":1756080572000},"page":"2741","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lactase Persistence-Associated rs4988235 Polymorphism: A Novel Genetic Link to Cardiovascular Risk via Modulation of ApoB100 and ApoAI"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3459-0173","authenticated-orcid":false,"given":"Nihad","family":"Kharrat Helu","sequence":"first","affiliation":[{"name":"Doctoral School of Health Sciences, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8271-2248","authenticated-orcid":false,"given":"Habib","family":"Al Ashkar","sequence":"additional","affiliation":[{"name":"Doctoral School of Health Sciences, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"HUN-REN-UD Public Health Research Group, Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9256-3756","authenticated-orcid":false,"given":"Nora","family":"Kovacs","sequence":"additional","affiliation":[{"name":"HUN-REN-UD Public Health Research Group, Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9679-6669","authenticated-orcid":false,"given":"Roza","family":"Adany","sequence":"additional","affiliation":[{"name":"HUN-REN-UD Public Health Research Group, Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"National Laboratory for Health Security, Center for Epidemiology and Surveillance, Semmelweis University, 1089 Budapest, Hungary"},{"name":"Institute of Preventive Medicine and Public Health, Semmelweis University, 1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5539-907X","authenticated-orcid":false,"given":"Peter","family":"Piko","sequence":"additional","affiliation":[{"name":"Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"National Laboratory for Health Security, Center for Epidemiology and Surveillance, Semmelweis University, 1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/ng826","article-title":"Identification of a variant associated with adult-type hypolactasia","volume":"30","author":"Enattah","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1093\/hmg\/ddg244","article-title":"Lactase persistence DNA variant enhances lactase promoter activity in vitro: Functional role as a cis regulatory element","volume":"12","author":"Olds","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1136\/gut.52.5.647","article-title":"Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult-type hypolactasia","volume":"52","author":"Kuokkanen","year":"2003","journal-title":"Gut"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.3748\/wjg.v13.i25.3508","article-title":"Correlation of intestinal disaccharidase activities with the C\/T variant and age","volume":"13","author":"Enattah","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/00365529409091740","article-title":"Genetics and epidemiology of adult-type hypolactasia","volume":"202","author":"Sahi","year":"1994","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/BF00292375","article-title":"Prevalence of primary adult lactose malabsorption in Hungary","volume":"64","author":"Czeizel","year":"1983","journal-title":"Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1217s","DOI":"10.3945\/ajcn.113.073007","article-title":"How sound is the science behind the dietary recommendations for dairy?","volume":"99","author":"Weaver","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Timon, C.M., O\u2019Connor, A., Bhargava, N., Gibney, E.R., and Feeney, E.L. (2020). Dairy Consumption and Metabolic Health. Nutrients, 12.","DOI":"10.20944\/preprints202008.0609.v1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11657-013-0119-2","article-title":"Milk and yogurt consumption are linked with higher bone mineral density but not with hip fracture: The Framingham Offspring Study","volume":"8","author":"Sahni","year":"2013","journal-title":"Arch. Osteoporos."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.3945\/ajcn.115.123216","article-title":"Consumption of dairy foods and diabetes incidence: A dose-response meta-analysis of observational studies","volume":"103","author":"Gijsbers","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"568","DOI":"10.2337\/dc18-2034","article-title":"Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study","volume":"42","author":"Vissers","year":"2019","journal-title":"Diabetes Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1093\/ajcn\/87.6.1914","article-title":"Ethnic differences in dairy and related nutrient consumption among US adults and their association with obesity, central obesity, and the metabolic syndrome","volume":"87","author":"Beydoun","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Salehi, Z., Ghosn, B., Namazi, N., and Azadbakht, L. (2025). Assessing the association between dairy consumption and the 10-year Framingham Risk Score in women. Bmc Nutr., 11.","DOI":"10.1186\/s40795-025-01050-0"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Micha\u00eblsson, K., Lemming, E.W., Larsson, S.C., H\u00f6ijer, J., Melhus, H., Svennblad, B., Baron, J.A., Wolk, A., and Byberg, L. (2024). Non-fermented and fermented milk intake in relation to risk of ischemic heart disease and to circulating cardiometabolic proteins in swedish women and men: Two prospective longitudinal cohort studies with 100,775 participants. BMC Med., 22.","DOI":"10.1186\/s12916-024-03651-1"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mullie, P., Pizot, C., and Autier, P. (2016). Daily milk consumption and all-cause mortality, coronary heart disease and stroke: A systematic review and meta-analysis of observational cohort studies. BMC Public Health, 16.","DOI":"10.1186\/s12889-016-3889-9"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10654-022-00937-7","article-title":"Milk intake, lactase persistence genotype, plasma proteins and risks of cardiovascular events in the Swedish general population","volume":"38","author":"Zhang","year":"2023","journal-title":"Eur. J. Epidemiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1017\/S0007114518002830","article-title":"Intake of fermented and non-fermented dairy products and risk of incident CHD: The Kuopio Ischaemic Heart Disease Risk Factor Study","volume":"120","author":"Koskinen","year":"2018","journal-title":"Br. J. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"G\u00f3rczy\u0144ska-Kosiorz, S., Cichocka, E., Niemiec, P., Trautsolt, W., Pluskiewicz, W., and Gumprecht, J. (2024). Bone Mineral Density and the Risk of Type-2 Diabetes in Postmenopausal Women: rs4988235 Polymorphism Associated with Lactose Intolerance Effects. Nutrients, 16.","DOI":"10.3390\/nu16173002"},{"key":"ref_19","first-page":"932","article-title":"The lactase rs4988235 is associated with obesity related variables and diabetes mellitus in menopausal obese females","volume":"25","author":"Izaola","year":"2021","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/ejcn.2017.8","article-title":"Genetically predicted milk consumption and bone health, ischemic heart disease and type 2 diabetes: A Mendelian randomization study","volume":"71","author":"Yang","year":"2017","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/ejcn.2016.164","article-title":"The lactase-13910C&gt;T polymorphism (rs4988235) is associated with overweight\/obesity and obesity-related variables in a population sample of Portuguese young adults","volume":"71","author":"Manco","year":"2017","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1093\/jn\/nxy246","article-title":"Maternal Lactase Polymorphism (rs4988235) Is Associated with Neural Tube Defects in Offspring in the National Birth Defects Prevention Study","volume":"149","author":"Hoang","year":"2019","journal-title":"J. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nolan, D.J., Han, D.Y., Lam, W.J., Morgan, A.R., Fraser, A.G., Tapsell, L.C., and Ferguson, L.R. (2010). Genetic adult lactase persistence is associated with risk of Crohn\u2019s Disease in a New Zealand population. BMC Res. Notes, 3.","DOI":"10.1186\/1756-0500-3-339"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"i2416","DOI":"10.1136\/bmj.i2416","article-title":"Prediction models for cardiovascular disease risk in the general population: Systematic review","volume":"353","author":"Damen","year":"2016","journal-title":"BMJ"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1093\/clinchem\/hvad012","article-title":"The Present and Future of Lipid Testing in Cardiovascular Risk Assessment","volume":"69","author":"Higgins","year":"2023","journal-title":"Clin. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"\u00c1d\u00e1ny, R., Pik\u00f3, P., Fiatal, S., K\u00f3sa, Z., S\u00e1ndor, J., B\u00edr\u00f3, \u00c9., K\u00f3sa, K., Paragh, G., B\u00e1csn\u00e9 B\u00e1ba, \u00c9., and Veres-Balajti, I. (2020). Prevalence of Insulin Resistance in the Hungarian General and Roma Populations as Defined by Using Data Generated in a Complex Health (Interview and Examination) Survey. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17134833"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Piko, P., Kosa, Z., Sandor, J., Seres, I., Paragh, G., and Adany, R. (2022). The profile of HDL-C subfractions and their association with cardiovascular risk in the Hungarian general and Roma populations. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-15192-9"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/S0140-6736(13)61752-3","article-title":"The Framingham Heart Study and the epidemiology of cardiovascular disease: A historical perspective","volume":"383","author":"Mahmood","year":"2014","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S0195-668X(03)00114-3","article-title":"Estimation of ten-year risk of fatal cardiovascular disease in Europe: The SCORE project","volume":"24","author":"Conroy","year":"2003","journal-title":"Eur. Heart J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1161\/CIRCULATIONAHA.107.699579","article-title":"General cardiovascular risk profile for use in primary care: The Framingham Heart Study","volume":"117","author":"Vasan","year":"2008","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1161\/01.cir.0000437741.48606.98","article-title":"2013 ACC\/AHA Guideline on the Assessment of Cardiovascular Risk A Report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines","volume":"129","author":"Goff","year":"2014","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20","DOI":"10.7326\/M17-3011","article-title":"Clinical Implications of Revised Pooled Cohort Equations for Estimating Atherosclerotic Cardiovascular Disease Risk","volume":"169","author":"Yadlowsky","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Piko, P., Kosa, Z., Sandor, J., and Adany, R. (2021). Comparative risk assessment for the development of cardiovascular diseases in the Hungarian general and Roma population. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-82689-0"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1145\/3447934.3447939","article-title":"The Usefulness of the Two-Step Normality Transformation in Retesting Existing Theories: Evidence on the Productivity Paradox","volume":"52","author":"Templeton","year":"2021","journal-title":"ACM SIGMIS Database DATABASE Adv. Inf. Syst."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/biomet\/41.1-2.133","article-title":"A distribution-free k-sample test against ordered alternatives","volume":"41","author":"Jonckheere","year":"1954","journal-title":"Biometrika"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1161\/CIRCRESAHA.115.306249","article-title":"Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology","volume":"118","author":"Nordestgaard","year":"2016","journal-title":"Circ. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1161\/JAHA.116.004947","article-title":"Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies","volume":"6","author":"Heianza","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.cmet.2013.01.003","article-title":"Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist","volume":"17","author":"Sayin","year":"2013","journal-title":"Cell Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11122","DOI":"10.1038\/ncomms11122","article-title":"Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA","volume":"7","author":"Kettunen","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1017\/S0007114508184677","article-title":"Genetic lactase non-persistence, consumption of milk products and intakes of milk nutrients in Finns from childhood to young adulthood","volume":"102","author":"Laaksonen","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.1017\/jns.2013.11","article-title":"Lactase non-persistence as a determinant of milk avoidance and calcium intake in children and adolescents","volume":"2","author":"Almon","year":"2013","journal-title":"J. Nutr. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Saleem, G.N., Gu, R.X., Qu, H.X., Khaskheli, G.B., Rajput, I.R., Qasim, M., and Chen, X. (2024). Therapeutic potential of popular fermented dairy products and its benefits on human health. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1328620"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1001\/jama.2017.0947","article-title":"Association Between Dietary Factors and Mortality From Heart Disease, Stroke, and Type 2 Diabetes in the United States","volume":"317","author":"Micha","year":"2017","journal-title":"JAMA"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Briggs, M.A., Petersen, K.S., and Kris-Etherton, P.M. (2017). Saturated Fatty Acids and Cardiovascular Disease: Replacements for Saturated Fat to Reduce Cardiovascular Risk. Healthcare, 5.","DOI":"10.20944\/preprints201705.0135.v1"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sonestedt, E., Born\u00e9, Y., Wirf\u00e4lt, E., and Ericson, U. (2021). Dairy Consumption, Lactase Persistence, and Mortality Risk in a Cohort From Southern Sweden. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.779034"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nrg3461","article-title":"Pleiotropy in complex traits: Challenges and strategies","volume":"14","author":"Solovieff","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6751","DOI":"10.3390\/nu7085309","article-title":"Adaptation to Lactose in Lactase Non Persistent People: Effects on Intolerance and the Relationship between Dairy Food Consumption and Evalution of Diseases","volume":"7","author":"Szilagyi","year":"2015","journal-title":"Nutrients"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1038\/sj.ejcn.1601663","article-title":"Fermentation, fermented foods and lactose intolerance","volume":"56","author":"Solomons","year":"2002","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Xu, H.T., Fang, F., Wu, K.Z., Song, J.P., Li, Y.Q., Lu, X.Y., Liu, J.C., Zhou, L.Y., Yu, W.Q., and Yu, F. (2023). Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia. Microbiome, 11.","DOI":"10.1186\/s40168-023-01709-5"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s11154-019-09512-0","article-title":"Dietary lipids, gut microbiota and lipid metabolism","volume":"20","author":"Schoeler","year":"2019","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1152\/physiolgenomics.00053.2017","article-title":"Genetic and microbiome influence on lipid metabolism and dyslipidemia","volume":"50","author":"Williams","year":"2018","journal-title":"Physiol. Genom."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.2147\/DDDT.S468147","article-title":"Impact of Lipids on Insulin Resistance: Insights from Human and Animal Studies","volume":"18","author":"Elkanawati","year":"2024","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1080\/10496505.2010.517154","article-title":"Bioactive Components in Milk and Dairy Products","volume":"11","author":"Charney","year":"2010","journal-title":"J. Agric. Food Inf."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Xu, T., Zhang, C., Yang, Y.F., Huang, L., Liu, Q.Y., Li, L., Zeng, Q.K., and Li, Z.P. (2024). Role of Milk Intake in Modulating Serum Lipid Profiles and Gut Metabolites. Metabolites, 14.","DOI":"10.3390\/metabo14120688"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1039\/C5FO00856E","article-title":"The mechanism of lowering cholesterol absorption by calcium studied by using an digestion model","volume":"7","author":"Vinarova","year":"2016","journal-title":"Food Funct."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1080\/10408398.2021.1954873","article-title":"Role of calcium on lipid digestion and serum lipids: A review","volume":"63","author":"Wilde","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1093\/nutrit\/nuab097","article-title":"Dairy bioactive proteins and peptides: A narrative review","volume":"79","author":"Auestad","year":"2021","journal-title":"Nutr. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Gigli, I. (2016). Casein Proteins: Structural and Functional Aspects. Milk Proteins\u2014From Structure to Biological Properties and Health Aspects, IntechOpen.","DOI":"10.5772\/60465"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1590\/1678-4685-gmb-2016-0071","article-title":"Frequency of adult type-associated lactase persistence LCT-13910C\/T genotypes in the Czech\/Slav and Czech Roma\/Gypsy populations","volume":"40","year":"2017","journal-title":"Genet. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1093\/eurpub\/ckw175.081","article-title":"Adult type associated lactase persistence genotypes in Czech and Roma\/Gypsy populations","volume":"26","author":"Hubacek","year":"2016","journal-title":"Eur. J. Public Health"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12944-015-0155-6","article-title":"The apoB100\/apoAI ratio is independently associated with the severity of coronary heart disease: A cross sectional study in patients undergoing coronary angiography","volume":"14","author":"Song","year":"2015","journal-title":"Lipids Health Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1001\/jamacardio.2019.3780","article-title":"Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review","volume":"4","author":"Sniderman","year":"2019","journal-title":"JAMA Cardiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1365-2796.2006.01643.x","article-title":"The apoB\/apoA-I ratio: A strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy--a review of the evidence","volume":"259","author":"Walldius","year":"2006","journal-title":"J. Intern. Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/17\/2741\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:35:15Z","timestamp":1760034915000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/17\/2741"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,24]]},"references-count":64,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["nu17172741"],"URL":"https:\/\/doi.org\/10.3390\/nu17172741","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,24]]}}}