Dataset Information

Genetically Regulated Bilirubin and Risk of Non-alcoholic Fatty Liver Disease: A Mendelian Randomization Study.

ABSTRACT: Mildly elevated serum bilirubin levels were reported to be associated with decreased risk of non-alcoholic fatty liver disease (NAFLD). Whether this is a causal relationship remains unclear. We tested the hypothesis that genetically elevated plasma bilirubin levels are causally related to reduce risk of NAFLD. A total of 403 eligible participants were enrolled. NAFLD was determined by liver ultrasonography. The uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene variants (UGT1A1 *6 and UGT1A1 *28) were genotyped through sequencing. We applied a Mendelian randomization approach to assess the effects of genetically elevated bilirubin levels on NAFLD. NAFLD was diagnosed in 19% of participants in our study (NAFLD = 76; Non-NAFLD = 327). The variants of UGT1A1 *28 and UGT1A1 *6 were strongly associated with increased total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IB) levels (each P < 0.001). These two common variants explain 12.7% (TB), 11.4% (IB), and 10.2% (DB) of the variance in bilirubin levels, respectively. In logistic regression model, after multifactorial adjustment for sex, age, aminotransferase (ALT), white blood count (WBC), and body mass index (BMI), variant UGT1A1 *28 (OR = 1.39; 95%CI: 0.614-3.170; P = 0.43) and UGT1A1 *6 (OR = 1.64, 95%CI, 0.78-3.44; P = 0.19) genotypes were not significantly associated with the risk of NAFLD. Moreover, the plasma bilirubin level (TB, IB, and DB) were not significantly associated with the risk of NAFLD (P > 0.30). A Mendelian randomization analysis of the UGT1A1 variants suggests that bilirubin is unlikely causally related with the risk of NAFLD.

SUBMITTER: Luo L

PROVIDER: S-EPMC6305545 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Genetically Regulated Bilirubin and Risk of Non-alcoholic Fatty Liver Disease: A Mendelian Randomization Study.

Luo Lei L An Ping P Jia Xinyong X Yue Xiaobian X Zheng Sujun S Liu Shuang S Chen Yu Y An Wei W Winkler Cheryl A CA Duan Zhongping Z

Frontiers in genetics 20181218

Mildly elevated serum bilirubin levels were reported to be associated with decreased risk of non-alcoholic fatty liver disease (NAFLD). Whether this is a causal relationship remains unclear. We tested the hypothesis that genetically elevated plasma bilirubin levels are causally related to reduce risk of NAFLD. A total of 403 eligible participants were enrolled. NAFLD was determined by liver ultrasonography. The uridine diphosphate glucuronosyltransferase 1A1 (<i>UGT1A1</i>) gene variants (<i>UGT ...[more]

PMID: 30619479

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Project description:Background and aimsVitamin C, as an antioxidant, may play a role in the treatment of NAFLD. This research aimed to investigate the association of serum vitamin C levels with the risk of NAFLD and to further examine the causal relationship by Mendelian randomization (MR) method.MethodsThe cross-sectional study selected 5,578 participants of the National Health and Nutrition Examination Survey (NHANES), 2005-2006 and 2017-2018. The association of serum vitamin C levels with NAFLD risk was evaluated under a multivariable logistic regression model. A two-sample MR study, using genetic data from large-scale genome-wide association studies (GWAS) of serum vitamin C levels (52,014 individuals) and NAFLD (primary analysis: 1,483 cases /17,781 controls; secondary analysis: 1,908 cases/340,591 controls), was conducted to infer causality between them. The inverse-variance-weighted (IVW) was applied as the main method of MR analysis. A series of sensitivity analyzes were used to evaluate the pleiotropy.ResultsIn the cross-sectional study, results showed that Tertile 3 group (Tertile 3: ≥1.06 mg/dl) had a significantly lower risk (OR = 0.59, 95% CI: 0.48 ~ 0.74, p < 0.001) of NAFLD than Tertile 1 group (Tertile 1: ≤0.69 mg/dl) after full adjustments. In regard to gender, serum vitamin C was protective against NAFLD in both women (OR = 0.63, 95% CI: 0.49 ~ 0.80, p < 0.001) and men (OR = 0.73, 95% CI: 0.55 ~ 0.97, p = 0.029) but was stronger among women. However, in the IVW of MR analyzes, no causal relationship between serum vitamin C levels and NAFLD risk was observed in the primary analysis (OR = 0.82, 95% CI: 0.47 ~ 1.45, p = 0.502) and secondary analysis (OR = 0.80, 95% CI: 0.53 ~ 1.22, p = 0.308). MR sensitivity analyzes yielded consistent results.ConclusionOur MR study did not support a causal association between serum vitamin C levels and NAFLD risk. Further studies with greater cases are warranted to confirm our findings.

Dataset Information

Genetically Regulated Bilirubin and Risk of Non-alcoholic Fatty Liver Disease: A Mendelian Randomization Study.

Publications

Genetically Regulated Bilirubin and Risk of Non-alcoholic Fatty Liver Disease: A Mendelian Randomization Study.

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