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Ji-Young Lee 1 Article
Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study
Christina Jeon, Ji-Young Lee, Sun Ju Lee, Keum Ji Jung, Heejin Kimm, Sun Ha Jee
Epidemiol Health. 2019;41:e2019034.   Published online July 12, 2019
DOI: https://doi.org/10.4178/epih.e2019034
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  • 7 Citations
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
OBJECTIVES
Bilirubin is an endogenous antioxidant that protects cells against oxidative stress. Increased plasma levels of bilirubin have been associated with a reduced risk of ischemic heart disease (IHD) in previous studies. Nonetheless, whether those associations reflect a true protective effect of bilirubin on IHD, rather than confounding or reverse causation, remains unknown. Therefore, we applied two-sample Mendelian randomization to evaluate the causal association between bilirubin levels and IHD risk in a Korean population.
METHODS
A total of 5 genetic variants—TRPM8 (rs10490012), USP40 (rs12993249), ATG16L1 (rs2119503), SLCO1B1 (rs4149014), and SLCO1B3 (rs73233620)—were selected as genetic instruments for serum bilirubin levels using a communitybased cohort, the Korean Genome and Epidemiology Study, comprising 33,598 subjects. We then evaluated their impact on IHD using the Korean Cancer Prevention Study-II cohort.
RESULTS
Among the 5 instrumental variables that showed significant associations with serum bilirubin levels, rs12993249 (USP40) showed the most significant association (p<2.36×10-105). However, we found no significant association between serum bilirubin levels and IHD. Sensitivity analyses demonstrated a consistent association, suggesting that our observations were robust.
CONCLUSIONS
Using two-sample Mendelian randomization, we found no association between serum bilirubin levels and IHD. Further studies that confirm the observed interactions among other ethnicities are warranted.
Summary
Korean summary
이 연구는 대규모 한국인 코호트를 이용하여, 빌리루빈과 허혈성 심장질환의 인과성을 규명한 연구결과이다. 특히 두 가지 자료를 이용한 멘델리안 무작위배정 연구방법을 적용하여, 한국인을 대상으로 빌리루빈과 허혈성 심장질환의 인과성을 처음으로 규명한 점이 큰 시사점을 가진다.
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Citations

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  • The Nonlinear Relationship Between Total Bilirubin and Coronary Heart Disease: A Dose-Response Meta-Analysis
    Chaoxiu Li, Wenying Wu, Yumeng Song, Shuang Xu, Xiaomei Wu
    Frontiers in Cardiovascular Medicine.2022;[Epub]     CrossRef
  • Another Reason to Cut Down on Alcohol?
    Hyeon Chang Kim
    Korean Circulation Journal.2022; 52(3): 231.     CrossRef
  • Serum bilirubin and kidney function: a Mendelian randomization study
    Sehoon Park, Soojin Lee, Yaerim Kim, Yeonhee Lee, Min Woo Kang, Kwangsoo Kim, Yong Chul Kim, Seung Seok Han, Hajeong Lee, Jung Pyo Lee, Kwon Wook Joo, Chun Soo Lim, Yon Su Kim, Dong Ki Kim
    Clinical Kidney Journal.2022; 15(9): 1755.     CrossRef
  • Heme Oxygenase-1 and Blood Bilirubin Are Gradually Activated by Oral D-Glyceric Acid
    O. Petteri Hirvonen, Maarit Lehti, Heikki Kyröläinen, Heikki Kainulainen
    Antioxidants.2022; 11(12): 2319.     CrossRef
  • Exploring the causal pathway from bilirubin to CVD and diabetes in the UK biobank cohort study: Observational findings and Mendelian randomization studies
    Lei Hou, Hongkai Li, Shucheng Si, Yuanyuan Yu, Xiaoru Sun, Xinhui Liu, Ran Yan, Yifan Yu, Chuan Wang, Fan Yang, Qing Wang, Fuzhong Xue
    Atherosclerosis.2021; 320: 112.     CrossRef
  • The causal association of bilirubin with cardiovascular disease: Are there still any questions?
    Claudia Lamina, Florian Kronenberg
    Atherosclerosis.2021; 320: 92.     CrossRef
  • Association between Alcohol Consumption and Serum Cortisol Levels: a Mendelian Randomization Study
    Jung-Ho Yang, Sun-Seog Kweon, Young-Hoon Lee, Seong-Woo Choi, So-Yeon Ryu, Hae-Sung Nam, Kyeong-Soo Park, Hye-Yeon Kim, Min-Ho Shin
    Journal of Korean Medical Science.2021;[Epub]     CrossRef

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