{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:45:36Z","timestamp":1760240736778,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T00:00:00Z","timestamp":1567382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Leading Team of Science and Technology Innovation","award":["2011R50021"],"award-info":[{"award-number":["2011R50021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Unfavorable serum lipid levels are the most important risk factors for coronary artery disease (CAD), cerebral infarction, and other cardiovascular and cerebrovascular diseases. This study included 2323 Han Chinese in southern China. We collected medical reports, lifestyle details, and blood samples of individuals and used the polymerase chain reaction-ligase detection reaction method to genotype single-nucleotide polymorphisms (SNPs). Two SNPs showed a strong evidence of association with total cholesterol (TC): rs1003723 and rs6413504 in the low-density lipoproteins receptor (LDLR). Two SNPs in LDLR showed a strong evidence of association with low-density lipoprotein cholesterol (LDL-C), rs1003723 and rs6413504. Two SNPs showed a strong evidence of association with triglycerides (TG), namely, rs662145 in pro-protein convertase subtilisin-kexin type 9 (PCSK9) and rs11643718 in the solute carrier family 12 member 3 (SLC12A3). For the TC, LDL-C, and TG levels, these SNPs generated strong combined effects on these lipid levels. For each additional dangerous gene, TC increased by 0.085 mmol\/L (p = 7.00 \u00d7 10\u22126), and LDL-C increased by 0.075 mmol\/L (p = 9.00 \u00d7 10\u22126). The TG increased by 0.096 mmol\/L (p = 2.90 \u00d7 10\u22125). Compared with those bearing no risk alleles, the risk of hypertriglyceridemia, hypercholesterolemia, and dyslipidemia increased in those with two or more risk alleles and one risk gene. Polymorphisms of PCSK9, LDLR, and SLC12A3 were associated with the plasma lipid levels in people in southern China. These results provide a theoretical basis for gene screening and the prevention of dyslipidemia.<\/jats:p>","DOI":"10.3390\/ijerph16173207","type":"journal-article","created":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T03:06:14Z","timestamp":1567479974000},"page":"3207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Polymorphisms in PCSK9, LDLR, BCMO1, SLC12A3, and KCNJ1 Are Associated with Serum Lipid Profile in Chinese Han Population"],"prefix":"10.3390","volume":"16","author":[{"given":"Zheng","family":"Li","sequence":"first","affiliation":[{"name":"Medical School, Hangzhou Normal University, Hangzhou 310000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4424-7959","authenticated-orcid":false,"given":"Tianyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Medical School, Hangzhou Normal University, Hangzhou 310000, China"},{"name":"Medical School, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3864-5301","authenticated-orcid":false,"given":"Xiaohua","family":"Tan","sequence":"additional","affiliation":[{"name":"Medical School, Hangzhou Normal University, Hangzhou 310000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Lei","sequence":"additional","affiliation":[{"name":"Medical School, Hangzhou Normal University, Hangzhou 310000, China"},{"name":"Medical School, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liu","family":"Huang","sequence":"additional","affiliation":[{"name":"Medical School, Hangzhou Normal University, Hangzhou 310000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Medical School, Hangzhou Normal University, Hangzhou 310000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2147\/VHRM.S176167","article-title":"Noncardiac lebanese hospitalized adult patients\u2019 awareness of their coronary artery disease risk factors","volume":"14","author":"Ghaddar","year":"2018","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/1538574416628654","article-title":"Dyslipidemia Part 1\u2014Review of Lipid Metabolism and Vascular Cell Physiology","volume":"50","author":"Helkin","year":"2016","journal-title":"Vasc. Endovasc. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"683","DOI":"10.2337\/diacare.24.4.683","article-title":"Cardiovascular morbidity and mortality associated with the metabolic syndrome","volume":"24","author":"Isomaa","year":"2001","journal-title":"Diabetes Care."},{"key":"ref_4","first-page":"707","article-title":"Biological, clinical and population relevance of 95 loci for blood lipids","volume":"466","author":"Stylianou","year":"2010","journal-title":"NIH Public Access."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yin, R.X., Li, Y.Y., Liu, W.Y., Zhang, L., and Wu, J.Z. (2011). Interactions of the apolipoprotein A5 gene polymorphisms and alcohol consumption on serum lipid levels. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017954"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1093\/oxfordjournals.aje.a113818","article-title":"The collaborative lipid research clinics program family study. IV. Familial associations of plasma lipids and lipoproteins","volume":"119","author":"Namboodiri","year":"1984","journal-title":"Am. J. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1056\/NEJM199304223281603","article-title":"Genetic and environmental influences on serum lipid levels in twins","volume":"16","author":"Heller","year":"1993","journal-title":"New England J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ng.269","article-title":"Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts","volume":"41","author":"Aulchenko","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ng.75","article-title":"Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans","volume":"40","author":"Kathiresan","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/ng.291","article-title":"Common variants at 30 loci contribute to polygenic dyslipidemia","volume":"41","author":"Kathiresan","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/ng.271","article-title":"Genome-wide association analysis of metabolic traits in a birth cohort from a founder population","volume":"41","author":"Sabatti","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/S0140-6736(08)60208-1","article-title":"LDL-cholesterol concentrations: a genome-wide association study","volume":"371","author":"Sandhu","year":"2008","journal-title":"Lancet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1126\/science.1142358","article-title":"Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels","volume":"316","author":"Saxena","year":"2017","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/ng.76","article-title":"Newly identified loci that influence lipid concentrations and risk of coronary artery disease","volume":"40","author":"Willer","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lye, S.H., Chahil, J.K., Bagali, P., Alex, L., Vadivelu, J., Ahmad, W.A.W., Chan, S.P., Thong, M.K., Zain, S.M., and Mohamed, R. (2013). Genetic polymorphisms in LDLR, APOB, PCSK9 and other lipid related genes associated with familial hypercholesterolemia in Malaysia. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060729"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1161\/ATVBAHA.110.203273","article-title":"Combined influence of LDLR and HMGCR sequence variation on lipid-lowering response to simvastatin","volume":"30","author":"Mangravite","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E682","DOI":"10.1002\/humu.21002","article-title":"The molecular basis of familial hypercholesterolemia in lebanon: Spectrum of LDLR mutations and role of PCSK9 as a modifier gene","volume":"7","author":"Abifadel","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1194\/jlr.M010009","article-title":"Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population","volume":"51","author":"Guella","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_19","first-page":"12","article-title":"Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults","volume":"1","author":"Clifford","year":"2013","journal-title":"Lipids Health Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/j.1464-5491.2004.01115.x","article-title":"Who and ATPIII proposals for the definition of the metabolic syndrome in patients with type 2 diabetes","volume":"21","author":"Marchesini","year":"2004","journal-title":"Diabet Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1073\/pnas.88.1.189","article-title":"Genetic disease detection and DNA amplification using cloned thermostable ligase","volume":"88","author":"Barany","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1128\/JCM.42.6.2403-2410.2004","article-title":"Development of a multiplex PCR-ligase detection reaction assay for diagnosis of infection by the four parasite species causing malaria in humans","volume":"42","author":"McNamara","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.meegid.2009.11.015","article-title":"Distribution of CCR5-\u039432, CCR5m303A, CCR2-64I and SDF1-3\u2032A in HIV-1 infected and uninfected high-risk Uighurs in Xinjiang, China","volume":"10","author":"Tan","year":"2010","journal-title":"Infect. Genet. Evol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1194\/jlr.P007476","article-title":"Effects of genetic variants on lipid parameters and dyslipidemia in a Chinese population","volume":"52","author":"Liu","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/opo.12131","article-title":"When to use the Bonferroni correction","volume":"34","author":"Armstrong","year":"2014","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1161\/ATVBAHA.109.201020","article-title":"Genetic variants influencing circulating lipid levels and risk of coronary artery disease","volume":"30","author":"Waterworth","year":"2010","journal-title":"Arterioscler Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/150358","article-title":"Association of polymorphisms of genes involved in lipid metabolism with blood pressure and lipid values in Mexican hypertensive individuals","volume":"2014","year":"2014","journal-title":"Dis. Markers"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/s12031-014-0238-2","article-title":"Effect of E670G polymorphism in PCSK9 gene on the risk and severity of coronary heart disease and ischemic stroke in a Tunisian cohort","volume":"53","author":"Slimani","year":"2014","journal-title":"J. Mol. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1093\/hmg\/5.9.1325","article-title":"Genetic variation at a splicing branch point in intron 9 of the low density lipoprotein (LDL)-receptor gene: A rare mutation that disrupts mRNA splicing in a patient with familial hypercholesterolaemia and a common polymorphism","volume":"5","author":"Webb","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1158\/1055-9965.EPI-07-2704","article-title":"Polymorphisms of genes in the lipid metabolism pathway and risk of biliary tract cancers and stones: a population-based case-control study in Shanghai, China","volume":"17","author":"Andreotti","year":"2008","journal-title":"Cancer Epidemiol. Prev. Biomark."},{"key":"ref_31","first-page":"7","article-title":"A rare missense mutation and a polymorphism with high frequency in LDLR gene among iranian patients with familial hypercholesterolemia","volume":"2","author":"Tajamolian","year":"2018","journal-title":"Adv. Biomed. Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ochoa, E., Iriondo, M., Manzano, C., Fullaondo, A., Villar, I., Ruiz-Irastorza, G., Zubiaga, A.M., and Estonba, A. (2016). LDLR and PCSK9 are associated with the presence of antiphospholipid antibodies and the development of thrombosis in aPLA carriers. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146990"},{"key":"ref_33","first-page":"12","article-title":"Database resources of the national center for biotechnology information","volume":"45","author":"Coordinators","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.biopha.2015.10.001","article-title":"L-Arginine and vitamin C attenuate pro-atherogenic effects of high-fat diet on biomarkers of endothelial dysfunction in rats","volume":"76","author":"Suliburska","year":"2015","journal-title":"Biomed. Pharmacother"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7864","DOI":"10.1038\/s41598-017-06104-3","article-title":"Dietary arginine affects the insulin signaling pathway, glucose metabolism and lipogenesis in juvenile blunt snout bream Megalobrama amblycephala","volume":"7","author":"Liang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11010-017-3120-z","article-title":"Arg913Gln of SLC12A3 gene promotes development and progression of end-stage renal disease in Chinese type 2 diabetes mellitus","volume":"437","author":"Zhang","year":"2018","journal-title":"Mol. Cell. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ajhg.2008.12.019","article-title":"Common variation in the \u03b2-carotene 15,15\u2032-monooxygenase 1 gene affects circulating levels of carotenoids: a genome-wide association study","volume":"84","author":"Ferrucci","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1475-2840-9-35","article-title":"KCNQ1 gene polymorphisms are associated with lipid parameters in a Chinese Han population","volume":"9","author":"Chen","year":"2010","journal-title":"Cardiovasc. Diabetol."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/17\/3207\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:16:10Z","timestamp":1760188570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/17\/3207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,2]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["ijerph16173207"],"URL":"https:\/\/doi.org\/10.3390\/ijerph16173207","relation":{},"ISSN":["1660-4601"],"issn-type":[{"type":"electronic","value":"1660-4601"}],"subject":[],"published":{"date-parts":[[2019,9,2]]}}}