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

Abstract

Introduction: Vitamin D binding protein (VDBP) is correlated with non-alcoholic fatty liver disease (NAFLD) through the biological functions of regulating plasma vitamin D (VD) level and the inflammatory process. Objective: This study aims to investigate the effects of VD level and VDBP gene polymorphisms on the risk of NAFLD in a Chinese population. Methods: Plasma 25-hydroxyvitamin D3 [25(OH)D3] levels were measured and seven VDBP 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 NAFLD case group by age and gender. Correlation analysis and multiple linear regression were used to screen determinants of 25(OH)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 (AUROC) and Hosmer-Lemeshow test. Results: Age, BMI and TG were independent factors influencing VD levels. Participants with low VD levels had significantly higher prevalence of NAFLD compared to subjects with normal VD levels (P < 0.001). A low VD level contributed to increased risk of NAFLD, independent of metabolic factors known to affect VD levels (adjusted OR = 2.282, 95% CI = 1.422-3.661, P = 0.001). Logistic regression analysis showed that individuals carrying rs7041-G allele had a significantly decreased risk of NAFLD occurrence compared to T allele (additive model: adjusted OR = 0.814, 95% CI = 0.713-0.929, P = 0.002; codominant model: adjusted OR = 0.623, 95% CI = 0.449-0.866, P = 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 VDBP SNP to assess NAFLD risk, an AUC of which being 0.817, significantly higher than the model not included VDBP SNP, with Hosmer-Lemeshow test fitting well (P = 0.182). Conclusions: Low plasma VD levels may increase susceptibility to NAFLD, while rs7041-G allele in VDBP contributed to a decreased NAFLD risk among Chinese population. The VDBP variant significantly improved the capability for NAFLD risk assessment, which could be used for early screening and management of NAFLD.

Vitamin D-related Genetic Variations and Non-alcoholic Fatty Liver Disease: a Systematic Review

“…A total of 19 records were further excluded at this stage since they did not report the outcome of interest. Finally, a total of 12 studies fulfilled the eligibility criteria [20][21][22][23][24][25][26][27][28][29][30][31].…”

“…A total of 12 studies consisting of at least 18,012 participants combined reported the outcome of interest [20][21][22][23][24][25][26][27][28][29][30][31]. These studies were conducted in 2010 to 2022.…”

“…These studies were conducted in 2010 to 2022. Four studies (two from the same population) are from China [26][27][28]31], three studies from the same group are from the United Kingdom [22][23][24], and the rest are from Australia [20], Germany, Iran [29], Japan [21] and United States [30]. The average age of participants varied from 13.8 to 55.0 years and the percentage of females varied from 16.7 to 60.0%.…”

“…The average age of participants varied from 13.8 to 55.0 years and the percentage of females varied from 16.7 to 60.0%. Five studies investigated the association between vitamin D-related genetic variations and presence of NAFLD [20,22,26,30,31], while 6 studies explored the relationship between the genetic variations and severity of NAFLD [22][23][24][25]30] and one study explored the influence of VDR genetic variation on response to calcitriol treatment [29]. Evaluations of NAFLD were performed by liver ultrasound in five studies [20,[27][28][29]31], liver biopsy in four studies [21][22][23][24] and abdominal computed tomography in one study [30].…”

“…Interestingly, variations of genes involved in vitamin D metabolism pathway described above have been shown to be associated with many conditions, such as coronary artery disease, osteoporosis, diabetes and autoimmune diseases, indicating the interaction between this pathway and health outcomes [16][17][18][19]. Additionally, a number of studies have reported the association between vitamin D-related genetic variations and NAFLD [20][21][22][23][24][25][26][27][28][29][30][31]. The objective of this systematic review was therefore to identify and summarize the results of all available studies that explored the association of vitamin D-related genetic polymorphisms with presence, severity and response to treatment of NAFLD.…”