(Download) "Association Between the UGT1A1 Ta-Repeat Polymorphism and Bilirubin Concentration in Patients with Intermittent Claudication: Results from the CAVASIC Study (Molecular Diagnostics and Genetics) (Clinical Report)" by Clinical Chemistry # eBook PDF Kindle ePub Free
eBook details
- Title: Association Between the UGT1A1 Ta-Repeat Polymorphism and Bilirubin Concentration in Patients with Intermittent Claudication: Results from the CAVASIC Study (Molecular Diagnostics and Genetics) (Clinical Report)
- Author : Clinical Chemistry
- Release Date : January 01, 2008
- Genre: Chemistry,Books,Science & Nature,
- Pages : * pages
- Size : 244 KB
Description
The heme degradation product bilirubin has potent antioxidative capacities that play a protective role in various diseases, including coronary artery and vascular disease (1, 2). Studies on the relationship between bilirubin concentration and cardiovascular disease have shown an inverse relationship between bilirubin concentration and atherosclerosis (3-13). Low bilirubin concentrations have also been independently and inversely related to impaired flow-mediated vasodilatation and increased carotid intima-media thickness in clinically healthy subjects (14, 15). These in vivo observations and experimental studies (16) suggest a protective effect of high physiological bilirubin concentrations on early steps in atherogenesis. By linkage analysis we recently identified a region on chromosome 2q significantly linked to bilirubin concentration (17), a finding that was subsequently confirmed by investigators for the Framingham Heart Study (18). The identified chromosomal region harbors the gene for the uridine diphosphate glucuronosyltransferase (UGT1A1, [6] UDP glucuronosyltransferase 1 family, polypeptide A1), the major enzyme of bilirubin glucuronidation, which mainly determines bilirubin elimination in humans. The activity of UGT1A1 is substantially influenced by a TA-repeat polymorphism in the UGT1A1 promoter (19). Individuals homozygous for 7 TA repeats (7/7) have lower promoter activity and higher subsequent bilirubin concentrations than heterozygous (6/7) or wild-type homozygous (6/6) individuals (19-21). In an investigation of the correlation between the TA-repeat polymorphism and the incidence of cardiovascular and coronary heart disease in the Framingham Offspring Study, we observed a statistically significant decreased risk for individuals with the 7/7 genotype (8).
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