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Elevated serum urate is a potential factor in reduction of total bilirubin: a Mendelian randomization study.

ABSTRACT: 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.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.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).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.

SUBMITTER: Zhang H

PROVIDER: S-EPMC5732772 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Elevated serum urate is a potential factor in reduction of total bilirubin: a Mendelian randomization study.

Zhang Hui H Liu Jing J Dong Zheng Z Ding Yue Y Qian Qiaoxia Q Zhou Jingru J Ma Yanyun Y Mei Zhendong Z Chen Xiangxiang X Li Yuan Y Yuan Ziyu Z Zhang Juan J Yang Yajun Y Chen Xingdong X Jin Li L Zou Hejian H Wang Xiaofeng X Wang Jiucun J

Oncotarget 20171024 61

<h4>Aim</h4>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.<h4>Materials and methods</h4>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 c ...[more]

PMID: 29262606

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Project description:BackgroundTo investigate the causal associations of serum urate (SUA) with stroke risk and prognosis using Mendelian randomization (MR) and the potential mediating role of stroke risk factors in the causal pathways.MethodsWe used the random-effects inverse variance weighting (IVW) as our primary method. We initially performed two-sample univariable MR (UVMR) to identify the causal associations of SUA (n = 437,354) with any stroke (AS, FinnGen: n = 311,635; MEGASTROKE: n = 446,696), ischemic stroke (IS, FinnGen: n = 212,774; MEGASTROKE: n = 440,328), intracranial hemorrhage (ICH, FinnGen: n = 343,663; ISGC: n = 3,026), functional outcome after ischemic stroke at 90d (n = 4,363), and motor recovery within 24 months after stroke (n = 488), and then multivariable MR (MVMR) to estimate the direct causal effects of SUA on these outcomes, adjusting for potential confounders. Finally, we further conducted a two-step MR to investigate the potential mediating role of body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and estimated glomerular filtration rate (eGFR) in the identified causal pathways.ResultsGenetically predicted elevated SUA levels were significantly associated with increased risk of AS (meta-analysis: OR = 1.09, 95% CI [1.04-1.13], p = 3.69e-05) and IS (meta-analysis: OR = 1.10, 95% CI [1.01-1.19], p = 0.021) and with improved poor functional outcome after ischemic stroke at 90d (OR = 0.81, 95% CI [0.72-0.90], p = 1.79e-04) and motor recovery within 24 months after stroke (OR = 1.42, 95% CI [1.23-1.64], p = 2.15e-06). In MVMR, SBP and DBP significantly attenuated the causal effects of SUA on AS, IS, and functional outcome after ischemic stroke at 90d and motor recovery within 24 months after stroke. Further mediation analyses showed that SBP mediated 52.4 and 34.5% of the effects of SUA on AS and IS, while DBP mediated 28.5 and 23.4% of the causal effects, respectively.ConclusionThis study supports the dual role of genetically predicted SUA in increasing stroke risk, especially ischemic stroke risk, and in improving functional outcome and motor recovery. SBP and DBP are key mediators lying on the causal pathways of SUA with AS and IS.

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Elevated serum urate is a potential factor in reduction of total bilirubin: a Mendelian randomization study.

Publications

Elevated serum urate is a potential factor in reduction of total bilirubin: a Mendelian randomization study.

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