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Original Articles
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
  • 11,728 View
  • 284 Download
  • 10 Web of Science
  • 10 Crossref
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.

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
    Xiao-Jie Zhang, He Fei, Chong-Yuan Sun, Ze-Feng Li, Zheng Li, Chun-Guang Guo, Dong-Bing Zhao
    World Journal of Gastrointestinal Surgery.2023; 15(10): 2247.     CrossRef
  • SLCO1B1 variants and the risk of antituberculosis drug-induced hepatotoxicity: a systematic review and meta-analysis
    Min Zhu, Xinyu Chen, Zhuolu Hao, Yiwen He, Bing Han, Shaowen Tang
    Pharmacogenomics.2023; 24(18): 931.     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
    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
Adiponectin is Associated with Impaired Fasting Glucose in the Non-Diabetic Population
Sang Yeun Kim, Sun Ju Lee, Hyoun Kyoung Park, Ji Eun Yun, Myoungsook Lee, Jidong Sung, Sun Ha Jee
Epidemiol Health. 2011;33:e2011007.   Published online August 20, 2011
DOI: https://doi.org/10.4178/epih/e2011007
  • 16,793 View
  • 112 Download
  • 7 Crossref
AbstractAbstract PDF
Abstract
<sec><title>OBJECTIVES</title><p>Adiponectin is strongly associated with diabetes in the Western population. However, whether adiponectin is independently associated with impaired fasting glucose (IFG) in the non-obese population is unknown.</p></sec><sec><title>METHODS</title><p>The serum adiponectin, insulin resistance (IR), and waist circumference (WC) of 27,549 healthy Koreans were measured. Individuals were then classified into tertile groups by gender. IFG was defined as a fasting serum glucose of 100-125 mg/dL without diabetes. IR was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). The association of adiponectin and IFG was determined using logistic regression analysis.</p></sec><sec><title>RESULTS</title><p>WC and adiponectin were associated with IFG in both men and women. However, the association of WC with IFG was attenuated in both men and women after adjustment for the HOMA-IR. Adiponectin was still associated with IFG after adjustment for and stratification by HOMA-IR in men and women. Strong combined associations of IR and adiponectin with IFG were observed in men and women. Multivariate adjusted odds ratios (ORs) (95% confidence interval [CI]) among those in the highest tertile of IR and the lowest tertile of adiponectin were 9.8 (7.96 to 12.07) for men and 24.1 (13.86 to 41.94) for women.</p></sec><sec><title>CONCLUSION</title><p>These results suggest that adiponectin is strongly associated with IFG, and point to adiponectin as an additional diagnostic biomarker of IFG in the non-diabetic population.</p></sec>
Summary

Citations

Citations to this article as recorded by  
  • Determination of risk factors associated with inflammation in hypertensive patients with type-2 diabetes mellitus in a Palestinian Diabetes Study
    Mohammed S. Ellulu, Ihab A. Naser, Sahar M. Abuhajar, Ahmed A. Najim
    Current Medical Research and Opinion.2021; 37(9): 1451.     CrossRef
  • Insulin and Proinsulin Dynamics Progressively Deteriorate From Within the Normal Range Toward Impaired Glucose Tolerance
    Norimitsu Murai, Naoko Saito, Eriko Kodama, Tatsuya Iida, Kentaro Mikura, Hideyuki Imai, Mariko Kaji, Mai Hashizume, Yasuyoshi Kigawa, Go Koizumi, Rie Tadokoro, Chiho Sugisawa, Kei Endo, Toru Iizaka, Ryo Saiki, Fumiko Otsuka, Shun Ishibashi, Shoichiro Nag
    Journal of the Endocrine Society.2020;[Epub]     CrossRef
  • Association between the level of circulating adiponectin and prediabetes: A meta‐analysis
    Huasheng Lai, Nie Lin, Zhenzhen Xing, Huanhuan Weng, Hua Zhang
    Journal of Diabetes Investigation.2015; 6(4): 416.     CrossRef
  • Comparison of salivary and plasma adiponectin and leptin in patients with metabolic syndrome
    Supanee Thanakun, Hisashi Watanabe, Sroisiri Thaweboon, Yuichi Izumi
    Diabetology & Metabolic Syndrome.2014;[Epub]     CrossRef
  • Adiponectin as predictor for diabetes among pre-diabetic groups
    Hyon-Suk Kim, Jaeseong Jo, Jung Eun Lim, Young Duk Yun, Soo Jin Baek, Tae-Yong Lee, Kap Bum Huh, Sun Ha Jee
    Endocrine.2013; 44(2): 411.     CrossRef
  • Attenuation of plasma annexin A1 in human obesity
    Anna Kosicka, Adam D. Cunliffe, Richard Mackenzie, M. Gulrez Zariwala, Mauro Perretti, Roderick J. Flower, Derek Renshaw
    The FASEB Journal.2013; 27(1): 368.     CrossRef
  • Association between ADIPOQ SNPs with plasma adiponectin and glucose homeostasis and adiposity phenotypes in the IRAS Family Study
    S. Sandy An, Anthony J.G. Hanley, Julie T. Ziegler, W. Mark Brown, Steven M. Haffner, Jill M. Norris, Jerome I. Rotter, Xiuqing Guo, Y.-D. Ida Chen, Lynne E. Wagenknecht, Carl D. Langefeld, Donald W. Bowden, Nicholette D. Palmer
    Molecular Genetics and Metabolism.2012; 107(4): 721.     CrossRef
Association between Alcohol Intake and Abdominal Obesity among the Korean Population
Mikyung Ryu, Heejin Kimm, Jaeseong Jo, Sun Ju Lee, Sun Ha Jee
Epidemiol Health. 2010;32:e2010007.   Published online May 19, 2010
DOI: https://doi.org/10.4178/epih/e2010007
  • 17,427 View
  • 115 Download
  • 14 Crossref
AbstractAbstract PDF
Abstract
<sec><title>OBJECTIVES</title><p>Although abdominal obesity has been reported to be highly related with alcohol intake, the results are still inconclusive. Therefore, this study was conducted to explore the association between alcohol and abdominal obesity among the Korean population.</p></sec><sec><title>METHODS</title><p>This study included 8,603 participants (men: 5,195, women: 3,408) aged 30 to 87 who visited the health promotion centers in Seoul for routine health examinations from April, 2006 to June, 2007. Abdominal obesity was defined as WC ≥90 cm for men and ≥85 cm for women in accordance with the Korean Society for the Study of Obesity. For ever drinkers, total alcohol consumption in grams was classified into four groups (group 1, non-drinkers; group 2, 1-10 g of alcohol per day; group 3, 11-20 g of alcohol per day; and group 4, over 20 g of alcohol per day).</p></sec><sec><title>RESULTS</title><p>The mean age of the study population was 45.4 yr old (men) and 45.3 yr (women). The average waist circumference was 85.3 cm in men and 75.3 cm in women. A high alcohol intake was associated with high waist circumference in both genders. In multivariate analysis, the group of men and women drinkers consuming >20 g in a day had a large waist circumference compared with men and women non-drinkers.</p></sec><sec><title>CONCLUSION</title><p>This study showed that a high alcohol intake was related to high waist circumference. Such association remained independently even after adjustment for smoking, which is strongly related to abdominal obesity.</p></sec>
Summary

Citations

Citations to this article as recorded by  
  • Measuring Racial Differences in Obesity Risk Factors in Non-Hispanic Black and White Men Aged 20 Years or Older
    Hossein Zare, Aida Aazami, Noran Shalby, Danielle R. Gilmore, Roland J. Thorpe
    American Journal of Men's Health.2023;[Epub]     CrossRef
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    Syed Shoeb Ahmad, Syed Mohammed Bilal, Anam Tariq, Aliya Rashid
    US Ophthalmic Review.2022; 16(1): 22.     CrossRef
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    Jeon Won Kwak, Chan Hee Jeon, Min Ho Kwak, Jeong Hyeon Kim, Yong Soon Park
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    Ludimila Garcia Souza, Thiago Veiga Jardim, Ana Carolina Rezende, Ana Luiza Lima Sousa, Humberto Graner Moreira, Naiana Borges Perillo, Samanta Garcia de Souza, Weimar Kunz Sebba Barroso de Souza, Ymara Cássia Luciana Araújo, Maria do Rosário Gondim Peixo
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    Yunji Hwang, Kyu Eun Lee, Elisabete Weiderpass, Young Joo Park, Young Jun Chai, Hyungju Kwon, Do Joon Park, BeLong Cho, Ho-Chun Choi, Daehee Kang, Sue K. Park, Li Wang
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  • Trends in the Incidence of Subarachnoid Hemorrhage in South Korea from 2006–2009: An Ecological Study
    Jin-Won Kwon, Hyun Joo Lee, Min Kyung Hyun, Ji Eun Choi, Jong Hee Kim, Na Rae Lee, Jin Seub Hwang, Eun Ju Lee
    World Neurosurgery.2013; 79(3-4): 499.     CrossRef
  • Adiponectin negatively correlates with alcoholic and non‐alcoholic liver dysfunction: Health check‐up study of Japanese men
    Mina Hamano, Yoshihiro Kamada, Shinichi Kiso, Kunimaro Furuta, Takashi Kizu, Norihiro Chatani, Mayumi Egawa, Takayo Takemura, Hisao Ezaki, Yuichi Yoshida, Kenji Watabe, Toshimitsu Hamasaki, Miyuki Umeda, Aiko Furubayashi, Kazuo Kinoshita, Osamu Kishida, T
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The Association Between Adiponectin and Diabetes in the Korean Population.
Sun Ha Jee, Hee Yeon Lee, Sun Ju Lee, Ji Eun Yun, Eun Jung Jee, Hye Yun Song, Sang Yeun Kim, Jungyong Park, Hyon Suk Kim
Korean J Epidemiol. 2007;29(2):176-186.
  • 65,535 View
  • 21 Download
AbstractAbstract PDF
Abstract
BACKGROUND
As indicators of obesity, waist circumference (WC), body mass index (BMI), and adiponectin are well known risk factor for diabetes mellitus. The objectives of this study were to measure the independent association between these obesity indicators and diabetes and to examine the combined effect of these indicators on diabetes in a Korean population.
METHODS
The WC, BMI, and serum adiponectin were measured in 6,505 healthy Koreans and were classified into tertile groups for men and women. The independent and combined associations of the obesity indicators with diabetes were measured using logistic regression analyses. Diabetes was defined as fasting serum glucose greater than 126 mg/dL or taking medication.
RESULTS
Levels of adiponectin were inversely associated with BMI and WC and directly associated with age and high density lipoprotein cholesterol (HDL) cholesterol (P <0.001). After adjusting for age, WC, and other lifestyle factors, low levels of adiponectin were associated with an increased prevalence of diabetes. Further adjustment for HDL cholesterol and triglyceride attenuated this association in both men and women. The best cut-off value of adiponectin in terms of identifying the presence of diabetes was 5.5 /ml with a sensitivity and specificity of 46.7% and 63.9% for men and 9.5 /ml with a sensitivity and specificity of 68.2% and 55.2 for women.
CONCLUSIONS
These results suggest that adiponectin was associated with diabetes. The association was independent of WC and was partly modified by HDL and triglyceride. There were no effect modifications of adiponectin with WC on diabetes.
Summary
Development of ELISA-kit of Quantitative Analysis for Adiponectin and Their Correlation with Cardiovascular Risk Factors.
Sun Ha Jee, Seungbok Lee, Sungsik Min, Jungyong Park, Hyon Suk Kim, Sang Yeun Kim, Ji Eun Yun, Sun Ju Lee, Eun Jung Jee, Hee Yeon Lee, Hye Yun Song
Korean J Epidemiol. 2007;29(2):165-175.
  • 40,569 View
  • 32 Download
AbstractAbstract PDF
Abstract
PURPOSE
S: To develop a rapid, sensitive, qualitative ELISA-kit for serum adiponectin and examine correlation with adiponectin and cardiovascular risk factors.
METHODS
On the base of monoclonal antibodies against adiponectin, apply indirect ELISA to study the performance parameter of the kit. The correlation was examined between adiponectin and cardiovascular risk factors including waist circumference, body mass index, triglyceride, and HDL cholesterol.
RESULTS
The limited concentration of detection of the ELISA-kit was 1ug/ml. Linearity with R&D system and AdipoGen with this ELISA-kit was acceptable: the linear equation with R&D system was y=1.0116x + 0.4629 (R2=0.97) and linear equation with AdipoGen was y=0.9562x + 1.1961 (R2=0.93), respectively. The average recovery rate of the ELISA-kit ranged 92 to 104%. The correlation coefficient of waist circumference with adiponectin was -0.2276 (p<0.0001) among men and -0.2328 (p<0.0001) among women.
CONCLUSION
This ELISA-kit was quick, sensitive, and stable and can be used to determine adiponectin in serum.
Summary
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