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

Minxian Wang; Ru Zhang; Min Wang; Liuxin Zhang; Yajie Ding; Zongzhe Tang; Hongliang Wang; Wei Zhang; Yue Chen; Jie Wang

doi:10.3389/fgene.2021.717533

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

Front Genet. 2021 Aug 16:12:717533. doi: 10.3389/fgene.2021.717533. eCollection 2021.

Authors

Minxian Wang¹, Ru Zhang¹, Min Wang¹, Liuxin Zhang², Yajie Ding¹, Zongzhe Tang¹, Hongliang Wang³, Wei Zhang⁴, Yue Chen¹, Jie Wang¹

Affiliations

¹ Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China.
² The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
³ Ninghai Road Community Health Service Center of Nanjing, Nanjing, China.
⁴ Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.

Abstract

Background: 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).

Objective: This study aims to investigate whether 11 candidate single nucleotide polymorphisms (SNPs) in vitamin D and calcium pathway genes (CYP2R1, CYP24A1, and CYP27B1) are associated with the risk of NAFLD.

Methods: 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 CYP2R1, CYP24A1, and CYP27B1 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.

Results: After adjusting for age, gender, and metabolic measures, we identified that CYP24A1 rs2296241 variant genotypes (recessive model: OR, 1.316; 95% CI, 1.048-1.653; p = 0.018), rs2248359 variant genotypes (recessive model: OR, 1.315; 95% CI, 1.033-1.674; p = 0.026), and CYP27B1 rs4646536 variant genotypes (additive model: OR, 1.147; 95% CI, 1.005-1.310; p = 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 (p_trend = 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 p < 0.05). The area under the receiver operating characteristic curve was 0.789 for all the above factors.

Conclusion: The polymorphisms of vitamin family genes CYP24A1 (rs2296241, CYP24A1, and rs2248359) and CYP27B1 (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.

Keywords: cytochrome P450 family 24 subfamily A member 1 gene; cytochrome P450 family 27 subfamily B member 1 gene; non-alcoholic fatty liver disease; polymorphism; risk.