AUTHOR=Wang Minxian , Zhang Ru , Wang Min , Zhang Liuxin , Ding Yajie , Tang Zongzhe , Wang Hongliang , Zhang Wei , Chen Yue , Wang Jie 

TITLE=Genetic Polymorphism of Vitamin D Family Genes CYP2R1, CYP24A1, and CYP27B1 Are Associated With a High Risk of Non-alcoholic Fatty Liver Disease: A Case-Control Study

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.717533

DOI=10.3389/fgene.2021.717533

ISSN=1664-8021

ABSTRACT=<sec><title>Background</title><p>Previous studies have highlighted the important role of vitamin D and calcium pathway genes in immune modulation, cell differentiation and proliferation, and inflammation regulation, all closely implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD).</p></sec><sec><title>Objective</title><p>This study aims to investigate whether 11 candidate single nucleotide polymorphisms (SNPs) in vitamin D and calcium pathway genes (<italic>CYP2R1</italic>, <italic>CYP24A1</italic>, and <italic>CYP27B1</italic>) are associated with the risk of NAFLD.</p></sec><sec><title>Methods</title><p>In this case-control study, a total of 3,023 subjects were enrolled, including 1,114 NAFLD cases and 1,909 controls. Eleven genetic variants in <italic>CYP2R1</italic>, <italic>CYP24A1</italic>, and <italic>CYP27B1</italic> genes were genotyped. Logistic regression analysis was used to assess the effects of these variants on NAFLD risk. The functional annotations of positive SNPs were further evaluated by bioinformatics analysis.</p></sec><sec><title>Results</title><p>After adjusting for age, gender, and metabolic measures, we identified that <italic>CYP24A1</italic> rs2296241 variant genotypes (recessive model: OR, 1.316; 95% CI, 1.048–1.653; <italic>p</italic> = 0.018), rs2248359 variant genotypes (recessive model: OR, 1.315; 95% CI, 1.033–1.674; <italic>p</italic> = 0.026), and <italic>CYP27B1</italic> rs4646536 variant genotypes (additive model: OR, 1.147; 95% CI, 1.005–1.310; <italic>p</italic> = 0.042) were associated with an elevated risk of NAFLD. In combined effects analysis, we found that NAFLD risk significantly increased among patients carrying more rs2296241-A, rs2248359-T, and rs4646536-T alleles (<italic>p</italic><sub>trend</sub> = 0.049). Multivariate stepwise analysis indicated that age, visceral obesity, ALT, γ-GT, hypertriglyceridemia, hypertension, low HDL-C, hyperglycemia, and unfavorable alleles were independent predictors of NAFLD (all <italic>p</italic> &lt; 0.05). The area under the receiver operating characteristic curve was 0.789 for all the above factors.</p></sec><sec><title>Conclusion</title><p>The polymorphisms of vitamin family genes <italic>CYP24A1</italic> (rs2296241, <italic>CYP24A1</italic>, and rs2248359) and <italic>CYP27B1</italic> (rs4646536) were associated with NAFLD risk in Chinese Han population, which might provide new insight into NAFLD pathogenesis and tools for screening high-risk population.</p></sec>