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

  1. Author:
    Luo, Lei
    An, Ping
    Jia, Xinyong
    Yue, Xiaobian
    Zheng, Sujun
    Liu, Shuang
    Chen, Yu
    An, Wei
    Winkler, Cheryl
    Duan, Zhongping

  2. Author Address

    The Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, China., Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China., Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States., The Department of Medical Laboratory, The Second Affiliated Hospital of Luohe Medical College, Luohe, China., The Department of Intensive Care Unit, The Second Affiliated Hospital of Luohe Medical College, Luohe, China., Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing, China., The Translational Hepatology Institute and College of Basic Medicine, Capital Medical University, Beijing, China., Department of Cell Biology and Municipal Laboratory of Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, China.,
    1. Year: 2018
    2. Date: Dec 18
    3. Epub Date: 2018 12 18
  2. Journal: Frontiers in genetics
    1. 9
    2. Pages: 662
  4. Type of Article: Article
  5. Article Number: 662
  6. ISSN: 1664-8021
  1. 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.

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External Sources

  1. View Full Text
  2. DOI: 10.3389/fgene.2018.00662
  3. PMID: 30619479
  4. PMCID: PMC6305545
  5. View record in Web of Science®
  6. WOS: 000453710200001

Library Notes

  1. Fiscal Year: FY2018-2019
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