Abstract
BackgroundIt has been demonstrated that vitamin D receptor (VDR), 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.ObjectivesTo investigate the effects of serum VD level, VDR variation, and a combination of VDR SNP and environmental behavior factor on the risk of NAFLD.MethodsA total of 3023 subjects from a community in Nanjing were enrolled, including 1120 NAFLD cases and 1903 controls. Serum 25(OH)D3 levels were measured and eight single nucleotide polymorphisms (SNPs) in VDR gene were genotyped.ResultsLogistic regression analyses indicated that VD sufficiency and VD insufficiency were significantly associated with a low risk of NAFLD (all P<0.05; all P trend <0.05, in a locus-dosage manner). After adjusting for gender and age, VDR rs2228570-A and rs11168287-A alleles were all reduced the risk of NAFLD (all P FDR=0.136, in dominant model; P trend =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 P<0.05). The area under the receiver operating curve of the combination of VDR SNP and exercise time for assessing NAFLD risk was slightly higher than that of only including exercise time or neither (all P<0.05).ConclusionHigh serum VD levels and VDR variants (rs2228570-A and rs11168287-A) might contribute to a low risk of NAFLD in Chinese Han population. The inclusion of VDR 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.
Highlights
Non-alcoholic fatty liver disease (NAFLD), as the most prevalent liver disease worldwide, comprises a wide disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) and NASH-related cirrhosis [1, 2]
Most patients with NAFLD are asymptomatic, and only few may complain of nonspecific symptoms, like discomfort, fatigue, and vague right upper abdominal pain [5], but NAFLD can increase the risk of type 2 diabetes mellitus (T2DM) as well as cardiovascular disease [6], and NASH may develop into fibrosis, even causing cirrhosis and hepatocellular carcinoma [7]
The subjects were distributed into two groups with “0” and “1-4” favorable alleles, and we found that the presence of “1-4” alleles was related to a 0.798-fold lower risk of NAFLD
Summary
Non-alcoholic fatty liver disease (NAFLD), as the most prevalent liver disease worldwide, comprises a wide disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) and NASH-related cirrhosis [1, 2]. Studies have increasingly found that vitamin D (VD) can affect the development of NAFLD by regulating IR [12], immune inflammation [13], lipid metabolism and target gene expression [14]. A population-based case-control study in China found that low serum VD was associated with advanced liver fibrosis in NAFLD patients [20]. A randomized, double-blind, placebo-controlled trial in Italy suggested that high-dose oral VD supplementation could increase the serum VD level, no effect was shown on hepatic steatosis or metabolic/cardiovascular parameters in T2DM patients with NAFLD [22]. It has been demonstrated that vitamin D receptor (VDR), 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
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