AUTHOR=Zhang Ru , Wang Minxian , Wang Min , Zhang Liuxin , Ding Yajie , Tang Zongzhe , Fu Zuqiang , Fan Haozhi , Zhang Wei , Wang Jie 

TITLE=Vitamin D Level and Vitamin D Receptor Genetic Variation Were Involved in the Risk of Non-Alcoholic Fatty Liver Disease: A Case-Control Study

JOURNAL=Frontiers in Endocrinology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.648844

DOI=10.3389/fendo.2021.648844

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>It has been demonstrated that vitamin D receptor (<italic>VDR</italic>), a key gene in the metabolism of vitamin D (VD), may affect the development of Non-alcoholic fatty liver disease (NAFLD) by regulating VD level and its biological effects.</p></sec><sec><title>Objectives</title><p>To investigate the effects of serum VD level, <italic>VDR</italic> variation, and a combination of <italic>VDR</italic> SNP and environmental behavior factor on the risk of NAFLD.</p></sec><sec><title>Methods</title><p>A total of 3023 subjects from a community in Nanjing were enrolled, including 1120 NAFLD cases and 1903 controls. Serum 25(OH)D<sub>3</sub> levels were measured and eight single nucleotide polymorphisms (SNPs) in <italic>VDR</italic> gene were genotyped.</p></sec><sec><title>Results</title><p>Logistic regression analyses indicated that VD sufficiency and VD insufficiency were significantly associated with a low risk of NAFLD (all <italic>P</italic>&lt;0.05; all <italic>P</italic><sub>trend</sub><italic>&lt;</italic>0.05, in a locus-dosage manner). After adjusting for gender and age, <italic>VDR</italic> rs2228570-A and rs11168287-A alleles were all reduced the risk of NAFLD (all <italic>P</italic><sub>FDR</sub>=0.136, in dominant model; <italic>P</italic><sub>trend</sub> =0.039, combined effects in a locus-dosage manner). The protective effects of two favorable alleles were more evident among subjects ≤40 years, non-hypertension, non-hyperglycemia and non-low high density lipoprotein-cholesterol (all <italic>P</italic>&lt;0.05). The area under the receiver operating curve of the combination of <italic>VDR</italic> SNP and exercise time for assessing NAFLD risk was slightly higher than that of only including exercise time or neither (all <italic>P</italic>&lt;0.05).</p></sec><sec><title>Conclusion</title><p>High serum VD levels and <italic>VDR</italic> variants (rs2228570-A and rs11168287-A) might contribute to a low risk of NAFLD in Chinese Han population. The inclusion of <italic>VDR</italic> SNP and exercise time could improve the efficiency in assessment of NAFLD risk, which might provide a novel perspective for early screening and preventing NAFLD.</p></sec>