ORIGINAL ARTICLESCommon variants of four bilirubin metabolism genes and their association with serum bilirubin and coronary artery disease in Chinese Han populationLin, Ronga; Wang, Yingb; Wang, Yia; Fu, Wenqinga; Zhang, Dandana; Zheng, Hongxianga; Yu, Tinga; Wang, Yingb; Shen, Minb; Lei, Rongb; Wu, Honge; Sun, Aijunf; Zhang, Ruifanga; Wang, Xiaofenga; Xiong, Momiaog; Huang, Weib; Jin, Lia c dAuthor Information aState Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Institutes of Biomedical Sciences, Fudan University bRuijin Hospital, School of Medicine, Shanghai Jiaotong University and Chinese National Human Genome Center at Shanghai cCAS-MPG Partner Institute of Computational Biology, SIBS, CAS, Shanghai dChina Medical City Institute of Health Sciences, Taizhou, Jiangsu eDepartment of Cardiology, Changhai Hospital, The Second Military Medical University fDepartment of Cardiology, Zhongshan Hospital, Fudan University, China gHuman Genetics Center, The University of Texas Health Science Center, Houston, USA Correspondence to Professor Li Jin, PhD, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China Tel: +86 21 6564 2419; fax: +86 21 6564 3714; e-mail: [email protected] Received 21 July 2008 Accepted 6 January 2009 Pharmacogenetics and Genomics: April 2009 - Volume 19 - Issue 4 - p 310-318 doi: 10.1097/FPC.0b013e328328f818 Buy Metrics Abstract Objectives Studies have revealed an inverse relationship between serum total bilirubin (TBIL) levels and coronary artery disease (CAD). This study investigated the genetic variants of four bilirubin metabolism genes — heme oxygenase-1 (HMOX1), biliverdin reductase A (BLVRA), solute carrier organic anion transporter family member 1B1 (SLCO1B1), and uridine diphosphate glycosyltransferase 1A1 (UGT1A1) — in relation to TBIL levels and CAD. Methods and results Thirty-five common single nucleotide polymorphisms (SNPs) were genotyped in 2380 unrelated Han participants who underwent angiocardiography at hospitals in Shanghai, China. Only three genetic variants — rs4399719 (UGT1A1 T-2473G), rs887829 (UGT1A1 G-364A), and rs4148323 (UGT1A1 G211A) — were associated with TBIL levels (each P<0.001). Four significant associations with CAD were detected after controlling age and the false discovery rate at 15%: the recessive effect of SNP rs887829 (UGT1A1 G-364A) [age-adjusted odds ratio (OR): 0.24; 95% confidence interval (CI): 0.10–0.60; P=0.0014] and dominant effect of rs4149013 (SLCO1B1 A-12099G) (age-adjusted OR: 0.70; 95% CI: 0.55–0.91; P=0.0069) on male CAD, and the additive effects of rs2877262 (BLVRA G+1238/in6C) (age-adjusted OR: 0.73; 95% CI: 0.59–0.89; P=0.0021) and rs2690381 (BLVRA G+2613/in6A) (age-adjusted OR: 0.70; 95% CI: 0.56–0.86; P=0.0008) on female CAD. SNPs rs2877262 and rs2690381 were both in a linkage disequilibrium block within BLVRA with r2 greater than 0.750. Correspondingly, this block was identified to be associated with female CAD. Conclusion Our study provides genetic evidences for the difference in the impact of these four bilirubin metabolism genes on TBIL levels and CAD. © 2009 Lippincott Williams & Wilkins, Inc.