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Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study
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Christina Jeon, Ji-Young Lee, Sun Ju Lee, Keum Ji Jung, Heejin Kimm, Sun Ha Jee
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Epidemiol Health. 2019;41:e2019034. Published online July 12, 2019
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DOI: https://doi.org/10.4178/epih.e2019034
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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.
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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
Citations to this article as recorded by  - Association of Different Total Bilirubin Levels with Prognosis of Peritoneal Dialysis-Associated Peritonitis
Yujian He, Jingjing Zhu, Fei Xiao, Qingyun Luo, Pengpeng Wang, Xu Wang, Yan He, Zibo Xiong
Medicina.2023; 59(10): 1837. CrossRef - Novel prognostic score based on the preoperative total bilirubin-albumin ratio and fibrinogen-albumin ratio in ampullary adenocarcinoma
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World Journal of Gastrointestinal Surgery.2023; 15(10): 2247. CrossRef - 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
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SLCO1B1
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The effect of smoking on lung cancer: ethnic differences and the smoking paradox
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Keum Ji Jung, Christina Jeon, Sun Ha Jee
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Epidemiol Health. 2016;38:e2016060. Published online December 20, 2016
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DOI: https://doi.org/10.4178/epih.e2016060
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29,290
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677
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49
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Abstract
The objectives of this review were to determine whether the smoking paradox still exists and to summarize possible explanations for the smoking paradox. Based on published data, we compared the risk of cigarette smoking for lung cancer in Western and Asian countries. We extracted data from the relevant studies about annual tobacco consumption, lung cancer mortality rates according to smoking status from each country, and possible explanations for the smoking paradox. A significantly greater risk of lung cancer death was found among current smokers in Asian countries than among nonsmokers, with relative risks (RRs) of 4.0 to 4.6 for Koreans, 3.7 to 5.1 for Japanese, and 2.4 to 6.5 for Chinese. Although a significantly greater risk of lung cancer was present among current smokers in Asian countries, the RRs in Asian countries were much lower than those reported in Western countries (range, 9.4 to 23.2). Possible explanations for the smoking paradox included epidemiologic characteristics, such as the smoking amount, age at smoking initiation, and the use of filtered or mild tobacco. The smoking paradox definitely exists, but may be explained by major epidemiologic characteristics. Therefore, the smoking paradox should not be interpreted as indicating that tobacco is safer or less harmful for Asians.
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Summary
Korean summary
흡연이 폐암에 미치는 관련성의 인종 차이
흡연은 폐암의 가장 큰 원인으로 알려져 있다. 그러나 흡연이 폐암에 미치는 관련성의 크기는 영국, 미국 등 서양에서 발표된 연구결과에서 10-20배 정도로 보고되고 있으나 한국, 일본, 중국 등 동양에서 발표된 연구에서 3-5배 정도로 낮게 보고되고 있다. 이러한 차이는 흡연유행, 담배성분, 흡연자 특성, 그리고 유전적인 차이로 일부 설명되고 있으나 아직 완전히 이해되어진 상태는 아니다. 이는 공중보건학적으로 매우 중요한 의미를 가지므로 동서양의 직접적인 비교연구가 필요할 것으로 생각된다.
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