Common variants of four bilirubin metabolism genes and their association with serum bilirubin and coronary artery disease in Chinese Han population.

摘要

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 r 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.