{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:08Z","timestamp":1787022188365,"version":"build-2736575974"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, BANBEIS GARE, Bangladesh","award":["LS20222111"],"award-info":[{"award-number":["LS20222111"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Acute myocardial infarction (AMI) remains a leading cause of cardiovascular morbidity and mortality worldwide. Emerging evidence highlights vitamin D as a critical determinant of cardiovascular health. The\n                    <jats:italic>CYP2R1<\/jats:italic>\n                    gene encodes the key 25-hydroxylase enzyme responsible for converting vitamin D to its principal circulating metabolite, 25-hydroxyvitamin D. However, the influence of\n                    <jats:italic>CYP2R1<\/jats:italic>\n                    polymorphisms on AMI susceptibility, particularly within South Asian populations, has not been well characterized. This study investigates the association of two\n                    <jats:italic>CYP2R1<\/jats:italic>\n                    variants, rs2060793 and rs12794714, with AMI risk and their relationship with serum vitamin D levels in a Bangladeshi cohort. A total of 502 participants comprising 251 AMI patients and 251 age- and sex-matched controls were analyzed. Genomic DNA was extracted and genotyped using PCR-RFLP, while serum 25-hydroxyvitamin D\n                    <jats:sub>3<\/jats:sub>\n                    levels were quantified by HPLC. AMI patients exhibited markedly lower vitamin D concentrations (23.92\u2009\u00b1\u20090.94\u2009ng\/mL) than controls (30.3\u2009\u00b1\u20090.86\u2009ng\/mL;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Genotypic analysis revealed a significant association between rs2060793 and AMI risk: the TC (OR = 2.49, 95% CI: 1.34\u20134.63) and CC (OR = 2.59, 95% CI: 1.37\u20134.90) genotypes conferred increased susceptibility compared to the TT genotype (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0064). The dominant model (TC\u2009+\u2009CC vs. TT) further confirmed this relationship (OR = 2.53, 95% CI: 1.39\u20134.61,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0016). In contrast, rs12794714 showed no significant association with AMI in this population. Stratified analysis indicated that rs2060793 was significantly linked to AMI in males but not females, while both variants were associated with increased risk in individuals aged \u226460 years, but not in those &gt;60 years. Bioinformatic and molecular docking analyses (RegulomeDB, JASPAR, HADDOCK 2.4, DNAproDB) further demonstrated potential regulatory effects of these variants on\n                    <jats:italic>CYP2R1<\/jats:italic>\n                    function. Collectively, our findings reveal a novel association between\n                    <jats:italic>CYP2R1<\/jats:italic>\n                    rs2060793 and vitamin D deficiency with AMI risk in the Bangladeshi population, underscoring the interplay of genetic and metabolic determinants in the molecular pathogenesis of AMI.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0350994","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:27:42Z","timestamp":1780680462000},"page":"e0350994","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic association and computational analysis of CYP2R1 gene polymorphisms rs2060793 and rs12794714 with vitamin D deficiency and acute myocardial infarction in the Bangladeshi population: A case control study"],"prefix":"10.1371","volume":"21","author":[{"given":"Sadia","family":"Akter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Nazid Bin","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2971-5283","authenticated-orcid":true,"given":"Zimam","family":"Mahmud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Tamanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Shakhawat Hossain","family":"Shawon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzana","family":"Ansari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3175-8709","authenticated-orcid":true,"given":"Md. Zakir Hossain","family":"Howlader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"pone.0350994.ref001","first-page":"27","article-title":"Acute myocardial infarction.","volume-title":"Gellman MD, Turner JR, editors. Encyclopedia of behavioral medicine","author":"S Ye","year":"2013"},{"issue":"18","key":"pone.0350994.ref002","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1016\/j.jacc.2018.08.1038","article-title":"Fourth universal definition of myocardial infarction","volume":"72","author":"K Thygesen","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"pone.0350994.ref003","unstructured":"World Health O. Cardiovascular diseases (CVDs). 2023."},{"key":"pone.0350994.ref004","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2147\/VHRM.S166111","article-title":"Prevalence of cardiovascular disease among Bangladeshi adult population: a systematic review and meta-analysis of the studies","volume":"14","author":"MZI Chowdhury","year":"2018","journal-title":"Vasc Health Risk Manag"},{"key":"pone.0350994.ref005","unstructured":"European Asylum Support O. Medical country of origin information report: Bangladesh - Cardiological conditions. 2024."},{"key":"pone.0350994.ref006","volume-title":"Cardiac biomarkers","author":"S Patibandla","year":"2024"},{"issue":"1","key":"pone.0350994.ref007","article-title":"Endothelial nitric oxide synthase gene G894T polymorphism and myocardial infarction: a meta-analysis of 34 studies involving 21,068 subjects","volume":"9","author":"J-Q Luo","year":"2014","journal-title":"PLoS One"},{"issue":"24","key":"pone.0350994.ref008","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1056\/NEJMoa1605086","article-title":"Genetic risk, adherence to a healthy lifestyle, and coronary disease","volume":"375","author":"AV Khera","year":"2016","journal-title":"New England J Med"},{"issue":"23","key":"pone.0350994.ref009","doi-asserted-by":"crossref","first-page":"11342","DOI":"10.1039\/D4FO03234A","article-title":"Correlation between vitamin D metabolic pathway-related gene polymorphisms and cardiovascular disease","volume":"15","author":"J Pang","year":"2024","journal-title":"Food Funct"},{"issue":"1","key":"pone.0350994.ref010","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1161\/HYPERTENSIONAHA.110.160929","article-title":"25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults","volume":"57","author":"KL Jablonski","year":"2011","journal-title":"Hypertension"},{"issue":"1","key":"pone.0350994.ref011","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1159\/000097812","article-title":"Vitamin D analogs modulate the expression of plasminogen activator inhibitor-1, thrombospondin-1 and thrombomodulin in human aortic smooth muscle cells","volume":"44","author":"JR Wu-Wong","year":"2007","journal-title":"J Vasc Res"},{"issue":"3","key":"pone.0350994.ref012","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.cyto.2008.12.009","article-title":"1Alpha,25-dihydroxyvitamin D3 inhibits CD40L-induced pro-inflammatory and immunomodulatory activity in human monocytes","volume":"45","author":"C Almerighi","year":"2009","journal-title":"Cytokine"},{"issue":"1","key":"pone.0350994.ref013","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1186\/s12872-025-05223-4","article-title":"Role of vitamin D supplementation in prevention of new onset atrial fibrillation in post-coronary artery bypass graft patients in vitamin D deficient and insufficient populations: a systematic review and meta-analysis","volume":"25","author":"N Lanka","year":"2025","journal-title":"BMC Cardiovasc Disord"},{"issue":"8","key":"pone.0350994.ref014","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1152\/japplphysiol.01506.2012","article-title":"Vitamin D signaling pathway plays an important role in the development of heart failure after myocardial infarction","volume":"114","author":"S Bae","year":"2013","journal-title":"J Appl Physiol (1985)"},{"issue":"4","key":"pone.0350994.ref015","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1161\/CIRCULATIONAHA.107.706127","article-title":"Vitamin D deficiency and risk of cardiovascular disease","volume":"117","author":"TJ Wang","year":"2008","journal-title":"Circulation"},{"issue":"5","key":"pone.0350994.ref016","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1365-2265.2011.04147.x","article-title":"Vitamin D, cardiovascular disease and mortality","volume":"75","author":"S Pilz","year":"2011","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"3","key":"pone.0350994.ref017","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.chembiol.2013.12.016","article-title":"Vitamin D metabolism, mechanism of action, and clinical applications","volume":"21","author":"D Bikle","year":"2014","journal-title":"Chemistry & Biology"},{"key":"pone.0350994.ref018","doi-asserted-by":"crossref","first-page":"94","DOI":"10.18433\/jpps31305","article-title":"The CYP2R1 enzyme: structure, function, enzymatic properties and genetic polymorphism","volume":"24","author":"AN Dong","year":"2021","journal-title":"J Pharm Pharm Sci"},{"issue":"1","key":"pone.0350994.ref019","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.bbrc.2004.09.073","article-title":"Metabolism of vitamin D by human microsomal CYP2R1","volume":"324","author":"R Shinkyo","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"issue":"39","key":"pone.0350994.ref020","doi-asserted-by":"crossref","first-page":"15650","DOI":"10.1073\/pnas.1315006110","article-title":"CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo","volume":"110","author":"JG Zhu","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pone.0350994.ref021","article-title":"Synonymous variants that disrupt messenger RNA structure are significantly constrained in the human population","volume":"10","author":"JBS Gaither","year":"2021","journal-title":"Gigascience"},{"issue":"8","key":"pone.0350994.ref022","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.3390\/genes13081485","article-title":"When a synonymous variant is nonsynonymous","volume":"13","author":"M Vihinen","year":"2022","journal-title":"Genes (Basel)"},{"issue":"1","key":"pone.0350994.ref023","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s13059-023-02966-1","article-title":"In silico methods for predicting functional synonymous variants","volume":"24","author":"BC Lin","year":"2023","journal-title":"Genome Biol"},{"issue":"6099","key":"pone.0350994.ref024","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1222794","article-title":"Systematic localization of common disease-associated variation in regulatory DNA","volume":"337","author":"MT Maurano","year":"2012","journal-title":"Science"},{"issue":"3","key":"pone.0350994.ref025","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0297138","article-title":"Vitamin D deficiency and the vitamin D receptor (VDR) gene polymorphism rs2228570 (FokI) are associated with an increased susceptibility to hypertension among the Bangladeshi population","volume":"19","author":"IK Nabil","year":"2024","journal-title":"PLoS One"},{"issue":"3","key":"pone.0350994.ref026","doi-asserted-by":"crossref","first-page":"265","DOI":"10.2174\/1389201019666180528082737","article-title":"Genetic Variants of CYP2R1 are key regulators of serum vitamin d levels and incidence of myocardial infarction in middle-aged Egyptians","volume":"19","author":"NK Sedky","year":"2018","journal-title":"Curr Pharm Biotechnol"},{"key":"pone.0350994.ref027","doi-asserted-by":"crossref","first-page":"652729","DOI":"10.3389\/fcvm.2021.652729","article-title":"Effect of cytochrome P450 family 2 Subfamily R Member 1 variants on the predisposition of coronary heart disease in the chinese han population","volume":"8","author":"Q Wang","year":"2021","journal-title":"Front Cardiovasc Med"},{"issue":"21","key":"pone.0350994.ref028","doi-asserted-by":"crossref","first-page":"4612","DOI":"10.3390\/nu14214612","article-title":"Association of CYP2R1 and VDR polymorphisms with metabolic syndrome components in non-diabetic brazilian adolescents","volume":"14","author":"S Ara\u00fajo EP dos","year":"2022","journal-title":"Nutrients"},{"key":"pone.0350994.ref029","article-title":"Pratical issues in calculating the sample size for prevalence studies","volume":"1","author":"L Naing","year":"2006","journal-title":"Arch Orofacial Sci"},{"issue":"4","key":"pone.0350994.ref030","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.ihj.2013.06.004","article-title":"Coronary artery disease in Bangladesh: a review","volume":"65","author":"AKMM Islam","year":"2013","journal-title":"Indian Heart J"},{"issue":"3","key":"pone.0350994.ref031","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S0735-1097(00)00804-4","article-title":"Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology\/American College of Cardiology Committee for the redefinition of myocardial infarction","volume":"36","author":"JS Alpert","year":"2000","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"pone.0350994.ref032","first-page":"5331474","article-title":"Troponin I cutoff for non-ST-segment elevation myocardial infarction in sepsis","volume":"2022","author":"MK Tsai","year":"2022","journal-title":"Mediators of Inflammation"},{"issue":"9","key":"pone.0350994.ref033","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1373\/49.9.1521","article-title":"Determination of 25-hydroxyvitamin D in serum by HPLC and immunoassay","volume":"49","author":"U Turpeinen","year":"2003","journal-title":"Clin Chem"},{"issue":"4","key":"pone.0350994.ref034","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1007\/s12291-024-01218-8","article-title":"The IKAROS transcription factor Gene IKZF1 as a critical regulator in the pathogenesis of childhood acute lymphoblastic leukemia: insights from a Bangladeshi Population","volume":"40","author":"NN Nila","year":"2025","journal-title":"Indian J Clin Biochem"},{"issue":"1","key":"pone.0350994.ref035","doi-asserted-by":"crossref","first-page":"27526","DOI":"10.1038\/s41598-025-13411-7","article-title":"Genetic and computational analysis of AKR1C4 gene rs17134592 polymorphism in breast cancer among the Bangladeshi population","volume":"15","author":"MA Shaon","year":"2025","journal-title":"Sci Rep"},{"key":"pone.0350994.ref036","first-page":"101992","article-title":"Deciphering the association of cholesteryl ester transfer protein (CETP) gene polymorphisms with high-density lipoprotein cholesterol (HDL-c) levels in the Bangladeshi population","volume":"42","author":"M Saiedullah","year":"2025","journal-title":"Biochem Biophys Rep"},{"issue":"3","key":"pone.0350994.ref037","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s12291-024-01264-2","article-title":"Exploring the Associations of Maternal and Neonatal eNOS Gene Variant rs2070744 with Nitric Oxide Levels, Oxidative Stress and Adverse Outcomes in Preeclampsia: a study in the Bangladeshi Population","volume":"40","author":"S Tamanna","year":"2025","journal-title":"Indian J Clin Biochem"},{"issue":"13","key":"pone.0350994.ref038","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1093\/nar\/gkg526","article-title":"NEBcutter: a program to cleave DNA with restriction enzymes","volume":"31","author":"T Vincze","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"pone.0350994.ref039","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.gene.2018.12.003","article-title":"Association of ATP binding cassette transporter 1 (ABCA 1) gene polymorphism with type 2 diabetes mellitus (T2DM) in Bangladeshi population","volume":"688","author":"MM Hasan","year":"2019","journal-title":"Gene"},{"issue":"6","key":"pone.0350994.ref040","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0318079","article-title":"Aldo-keto reductase family 1 member C3 (AKR1C3) gene polymorphism (rs12529) is associated with breast cancer in Bangladeshi population: A case-control study and computational investigation","volume":"20","author":"MA Shaon","year":"2025","journal-title":"PLoS One"},{"key":"pone.0350994.ref041","doi-asserted-by":"crossref","first-page":"101981","DOI":"10.1016\/j.genrep.2024.101981","article-title":"Single nucleotide variants rs7975232 and rs2228570 within vitamin D receptor gene confers protection against severity of COVID-19 infection in Bangladeshi population","volume":"36","author":"AA Saba","year":"2024","journal-title":"Gene Reports"},{"issue":"1","key":"pone.0350994.ref042","doi-asserted-by":"crossref","first-page":"24232","DOI":"10.1038\/s41598-024-75656-y","article-title":"Genetic association and computational analysis of MTHFR gene polymorphisms rs1801131 and rs1801133 with breast cancer in the Bangladeshi population","volume":"14","author":"NF Alam","year":"2024","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0350994.ref043","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/s41588-023-01365-3","article-title":"Annotating and prioritizing human non-coding variants with RegulomeDB v.2","volume":"55","author":"S Dong","year":"2023","journal-title":"Nat Genet"},{"key":"pone.0350994.ref044","first-page":"102502","article-title":"Comprehensive analysis of the deleterious nonsynonymous, non-coding SNPs and cancer variants of human aldo-keto reductase type 1 (AKR1C1) protein and their probable association with disease risk and progression: a computational study","volume":"45","author":"NN Nila","year":"2026","journal-title":"Biochem Biophys Rep"},{"key":"pone.0350994.ref045","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkad1059","article-title":"JASPAR 2024: 20th anniversary of the open-access database of transcription factor binding profiles","volume":"52","author":"I Rauluseviciute","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"pone.0350994.ref046","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jsb.2011.09.006","article-title":"UCSF Chimera, MODELLER, and IMP: an integrated modeling system","volume":"179","author":"Z Yang","year":"2012","journal-title":"J Struct Biol"},{"issue":"1","key":"pone.0350994.ref047","doi-asserted-by":"crossref","first-page":"22","DOI":"10.24198\/ijcb.v2i1.46322","article-title":"Molecular interaction analysis and visualization of protein-ligand docking using Biovia Discovery Studio Visualizer","volume":"2","author":"S Baroroh","year":"2023","journal-title":"IJCB"},{"key":"pone.0350994.ref048","article-title":"UniProt: the universal protein knowledgebase in 2023","volume":"51","author":"TU Consortium","year":"2022","journal-title":"Nucleic Acids Research"},{"issue":"7","key":"pone.0350994.ref049","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1021\/ja026939x","article-title":"HADDOCK: a protein-protein docking approach based on biochemical or biophysical information","volume":"125","author":"C Dominguez","year":"2003","journal-title":"J Am Chem Soc"},{"key":"pone.0350994.ref050","first-page":"101972","article-title":"Comprehensive in silico characterization of nonsynonymous SNPs in the human ezrin (EZR) gene and their role in disease pathogenesis","volume":"42","author":"S Akter","year":"2025","journal-title":"Biochem Biophys Rep"},{"issue":"2","key":"pone.0350994.ref051","doi-asserted-by":"crossref","first-page":"100686","DOI":"10.1016\/j.jgeb.2026.100686","article-title":"A comprehensive in silico investigation into the deleterious nonsynonymous single nucleotide polymorphisms of the human transcription factor EB (TFEB) gene and their predicted association with cancer","volume":"24","author":"M Fuad","year":"2026","journal-title":"J Genetic Eng Biotech"},{"key":"pone.0350994.ref052","article-title":"DNAproDB: an expanded database and web-based tool for structural analysis of DNA-protein complexes","volume":"48","author":"JM Sagendorf","year":"2020","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"pone.0350994.ref053","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0309713","article-title":"A comprehensive in silico investigation into the pathogenic SNPs in the RTEL1 gene and their biological consequences","volume":"19","author":"RR Tanshee","year":"2024","journal-title":"PLoS One"},{"issue":"8","key":"pone.0350994.ref054","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1210\/clinem\/dgae290","article-title":"Vitamin D for the prevention of disease: an endocrine society clinical practice guideline","volume":"109","author":"MB Demay","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"pone.0350994.ref055","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ajhg.2017.06.014","article-title":"Low-frequency synonymous coding variation in CYP2R1 has large effects on vitamin D levels and risk of multiple sclerosis","volume":"101","author":"D Manousaki","year":"2017","journal-title":"Am J Hum Genet"},{"issue":"1","key":"pone.0350994.ref056","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41572-019-0106-z","article-title":"Atherosclerosis","volume":"5","author":"P Libby","year":"2019","journal-title":"Nature Rev Disease Primers"},{"key":"pone.0350994.ref057","doi-asserted-by":"crossref","first-page":"745539","DOI":"10.3389\/fcvm.2021.745539","article-title":"The associations of lipid profiles with cardiovascular diseases and death in a 10-year prospective cohort study","volume":"8","author":"J Dong","year":"2021","journal-title":"Front Cardiovasc Med"},{"issue":"3","key":"pone.0350994.ref058","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ejvs.2012.06.017","article-title":"Vitamin D deficiency may be an independent risk factor for arterial disease","volume":"44","author":"KM van de Luijtgaarden","year":"2012","journal-title":"Eur J Vasc Endovasc Surg"},{"issue":"4","key":"pone.0350994.ref059","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/s41430-018-0088-z","article-title":"Exploring the association between serum 25-hydroxyvitamin D and serum lipids-more than confounding?","volume":"72","author":"R Jorde","year":"2018","journal-title":"Eur J Clin Nutr"},{"issue":"2","key":"pone.0350994.ref060","first-page":"167","article-title":"Vitamin D deficiency in Bangladesh: a review of prevalence, causes and recommendations for mitigation","volume":"31","author":"MZ Islam","year":"2022","journal-title":"Asia Pac J Clin Nutr"},{"issue":"9","key":"pone.0350994.ref061","article-title":"Acute myocardial infarction in young individuals: demographic and risk factor profile, clinical features, angiographic findings and in-hospital outcome","volume":"15","author":"IN Dimitrova","year":"2023","journal-title":"Cureus"},{"issue":"7","key":"pone.0350994.ref062","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1093\/chromsci\/bmw048","article-title":"Stability-Indicating HPLC-UV Method for Vitamin D3 Determination in Solutions, Nutritional Supplements and Pharmaceuticals","volume":"54","author":"\u017d Temova","year":"2016","journal-title":"J Chromatogr Sci"},{"key":"pone.0350994.ref063","unstructured":"Letter W. Common reasons for HPLC retention time drift, variation or change. 2015."},{"issue":"1","key":"pone.0350994.ref064","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.numecd.2021.11.003","article-title":"The influence of CYP2R1 polymorphisms and gene-obesity interaction with hypertension risk in a Chinese rural population","volume":"32","author":"Z Xu","year":"2022","journal-title":"Nutr Metab Cardiovasc Dis"},{"issue":"21","key":"pone.0350994.ref065","article-title":"Obesity and cardiovascular disease: a scientific statement from the American Heart Association","volume":"143","author":"TM Powell-Wiley","year":"2021","journal-title":"Circulation"},{"issue":"10","key":"pone.0350994.ref066","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.3390\/genes12101530","article-title":"Risk allele frequency analysis of single-nucleotide polymorphisms for vitamin D concentrations in different ethnic group","volume":"12","author":"B-W Yoon","year":"2021","journal-title":"Genes (Basel)"},{"issue":"11","key":"pone.0350994.ref067","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1017\/S0007114522000149","article-title":"Sex differences in vitamin D metabolism, serum levels and action","volume":"128","author":"A Wierzbicka","year":"2022","journal-title":"Br J Nutr"},{"key":"pone.0350994.ref068","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.atherosclerosis.2017.01.010","article-title":"A 45-SNP genetic risk score is increased in early-onset coronary artery disease but independent of familial disease clustering","volume":"257","author":"MK Christiansen","year":"2017","journal-title":"Atherosclerosis"},{"issue":"7139","key":"pone.0350994.ref069","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1136\/bmj.316.7139.1236","article-title":"What\u2019s wrong with Bonferroni adjustments","volume":"316","author":"TV Perneger","year":"1998","journal-title":"BMJ"},{"issue":"3","key":"pone.0350994.ref070","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1053\/jhep.2001.22176","article-title":"Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes: a study using adenovirus-mediated antisense targeting","volume":"33","author":"R Jover","year":"2001","journal-title":"Hepatology"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0350994","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:27:55Z","timestamp":1780680475000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0350994"}},"subtitle":[],"editor":[{"given":"Ramu","family":"Adela","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":70,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0350994","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]}}}