Elevated serum urate is a potential factor in reduction of total bilirubin: a Mendelian randomization study
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Hui Zhang1,*, Jing Liu1,*, Zheng Dong1,*, Yue Ding2, Qiaoxia Qian2, Jingru Zhou2, Yanyun Ma2, Zhendong Mei1, Xiangxiang Chen1, Yuan Li1, Ziyu Yuan3, Juan Zhang3, Yajun Yang2,3, Xingdong Chen1,3, Li Jin1,3, Hejian Zou4,5, Xiaofeng Wang1,3 and Jiucun Wang1,3,5
1State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
2Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
3Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
4Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China
5Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China
*These authors contributed equally to this work
Jiucun Wang, email: [email protected]
Xiaofeng Wang, email: [email protected]
Keywords: serum urate, total bilirubin, mendelian randomization study
Received: August 29, 2016 Accepted: October 03, 2017 Published: October 24, 2017
Aim: A Mendelian randomization study (MRS) can be linked to a “natural” randomized controlled trial in order to avoid potential bias of observational epidemiology. We aimed to study the possible association between serum urate (SU) and total bilirubin (TBIL) using MRS.
Materials and Methods: An observational epidemiological study using ordinary least squares (OLS) regression and MRS using two-stage least square (TLS) regression was conducted to assess the effect of SU on TBIL. The comparison between the OLS regression and the TLS regression was analyzed by the Durbin-Hausman test. If the p value is significant, it suggests that the OLS regression cannot evaluate the relationship between exposure and outcome, and the TLS regression is precise; while if the p value is not significant, there would be no significant difference between the two regressions.
Results: A total of 3,753 subjects were analyzed. In OLS regression, there was no significant association between SU and TBIL in all subjects and subgroup analysis (all p > 0.05). However, MRS revealed a negative correlation between SU and TBIL after adjustment for confounders (beta = –0.021, p = 0.010). Further analysis was conducted in different SU subgroups, and results show that elevated SU was associated with a significant reduction in TBIL after adjustment for hyperuricemic subjects (beta = –0.053, p = 0.027). In addition, the results using the Durbin-Hausman test further confirmed a negative effect of SU on TBIL (p = 0.002 and 0.010, respectively).
Conclusions: This research shows for the first time that elevated SU was a potential causal factor in the reduction of TBIL and it provides strong evidence to resolve the controversial association between SU and TBIL.
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