Abstract
AimA 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 MethodsAn 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.ResultsA 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).ConclusionsThis 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.
Highlights
Uric acid is the end-product of purine metabolism in humans and is controlled by several genetic factors [1], such as ABCG2 and SLC2A9 [2]
In ordinary least squares (OLS) regression, there was no significant association between serum urate (SU) and total bilirubin (TBIL) in all subjects and subgroup analysis
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
Summary
Uric acid is the end-product of purine metabolism in humans and is controlled by several genetic factors [1], such as ABCG2 and SLC2A9 [2]. It has been reported that hyperuricemia can be one of the factors inducing oxidative stress followed by a pro-inflammatory process and endocrine dysfunction in adipose tissue [3]. Observational studies about the relationship between serum urate (SU) and total bilirubin (TBIL) levels were controversial. An observational study conducted in Korea has suggested that SU positively correlates with TBIL levels [8]. Two reports found no association between SU and TBIL in Korea and Japan [9, 10]. It was difficult to confirm whether SU was a real mediator of TBIL or whether the observed relationship between SU and TBIL was attributable to confounders. It is difficult to confirm whether SU is a real causal of TBIL or whether the observed relationship between SU and TBIL was attributable to confounders
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