Influences of Vitamin D Levels and Vitamin D-Binding Protein Polymorphisms on Nonalcoholic Fatty Liver Disease Risk in a Chinese Population

Abstract

<b><i>Introduction:</i></b> Vitamin D-binding protein (VDBP) is correlated with nonalcoholic fatty liver disease (NAFLD) through the biological functions of regulating plasma vitamin D (VD) level and the inflammatory process. <b><i>Objective:</i></b> This study aims to investigate the effects of VD level and <i>VDBP</i> gene polymorphisms on the risk of NAFLD in a Chinese population. <b><i>Methods:</i></b> Plasma 25-hydroxyvitamin D₃ levels were measured and seven <i>VDBP</i> candidate genetic variants (rs222020, rs2282679, rs4588, rs1155563, rs7041, rs16847024, rs3733359) were genotyped among participants in this case-control study. The control group was frequency-matched to the NAFLD case group by age and gender. Correlation analysis and multiple linear regressions were used to screen determinants of 25-hydroxyvitamin D₃ levels. Multivariable unconditional logistic regression was performed to estimate odds ratio (OR) and 95% confidence interval (95% CI). The prediction capability of models containing independent factors was estimated by the area under the receiver operating characteristic curve and Hosmer-Lemeshow test. <b><i>Results:</i></b> Age, body mass index, and triacylglycerol were independent factors influencing VD levels. Participants with low VD levels had significantly higher prevalence of NAFLD compared to subjects with normal VD levels (<i>p</i> &#x3c; 0.001). A low VD level contributed to increased the risk of NAFLD, independent of metabolic factors known to affect VD levels (adjusted OR = 2.282, 95% CI = 1.422–3.661, <i>p</i> = 0.001). Logistic regression analysis showed that individuals carrying rs7041-G allele had a significantly decreased the risk of NAFLD occurrence compared to T allele (additive model: adjusted OR = 0.814, 95% CI = 0.713–0.929, <i>p</i> = 0.002; codominant model: adjusted OR = 0.623, 95% CI = 0.449–0.866, <i>p</i> = 0.005), after adjusting for age, gender, and overweight. Stratification by multiple metabolic disorders did not alter this relationship. Moreover, we developed a simple model including age, gender, metabolic disorders, and <i>VDBP</i> single nucleotide polymorphism (SNP) to assess NAFLD risk, an AUC of which being 0.817, significantly higher than the model not included <i>VDBP</i> SNP, with Hosmer-Lemeshow test fitting well (<i>p</i> = 0.182). <b><i>Conclusions:</i></b> Low plasma VD levels may increase susceptibility to NAFLD, while rs7041-G allele in <i>VDBP</i> contributed to a decreased NAFLD risk among Chinese population. The <i>VDBP</i> variant significantly improved the capability for NAFLD risk assessment, which could be used for early screening and management of NAFLD.