摘要
背景:胆红素是可抑制脂质氧化和延缓动脉粥样硬化形成的抗氧化剂。已有报道指出血清胆红素与冠心病间呈负相关。连锁研究已确定了位于染色体2q端粒、影响胆红素浓度的一个主要基因位点。
BACKGROUND -Bilirubin is an antioxidant that suppresses lipid oxidation and retards atherosclerosis formation. An inverse association between serum bilirubin and coronary heart disease has been reported. Linkage studies have identified a major locus at the chromosome 2q telomere that affects bilirubin concentrations. A candidate gene in the linkage region encodes hepatic bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1). The insertion of a TA in the TATAA box of the gene, an allele designated UGT1A128, decreases gene transcription. Individuals homozygous for UGT1A1*28 (genotype 7/7) have increased serum bilirubin levels compared with carriers of the 6 allele. To date, no significant association between UGT1A128 and cardiovascular disease (CVD) events has been reported. We performed an association study in the Framingham Heart Study population to investigate whether UGT1A128 is associated with the risk of CVD events. METHODS AND RESULTS -The study population included 1780 unrelated individuals from the Offspring cohort (49%males, mean age 36 years at entry) who had been followed up for 24 years. Individuals with genotype 7/7 had significantly higher bilirubin levels (mean±SD 1.14±0.44 mg/dL) than those with genotypes 6/6 and 6/7 (mean±SD 0.69±0.27 mg/dL, P < 0.01). Using the Cox proportional hazards model, we found significant associations between the UGT1A128 allele and decreased risk of CVD. Individuals with genotype 7/7 (population frequency of 11%) had approximately one third the risk for CVD and coronary heart disease as carriers of the 6 allele, which resulted in a hazard ratio (95%confidence interval) of 0.36 (0.18 to 0.74) and 0.30 (0.12 to 0.74), respectively. CONCLUSIONS -Homozy-gote UGT1A128 allele carriers with higher serum bilirubin concentrations exhibit a strong association with lower risk of CVD.
