Abstract
Abstract: :
Purpose: Age–related macular degeneration (AMD) is a complex degenerative disorder in which both environmental and genetic factors have been implicated. Various single nucleotide polymorphisms (SNPs) have been correlated with other degenerative and age–related diseases, many of which now serve as the focus of AMD candidate gene association studies. The correlation of SNPs in oxidative stress with AMD has been previously reported. The human ogg1 and CSB (Cockayne Syndrome Group B) genes are known to collaborate in the repair of oxidatively–damaged DNA. Recently, we identified a SNP association between AMD and CX3CR1, a chemokine receptor with cellular adhesion function (Tuo, 2004 Keystone Symposium J1). E–selectin is an adhesion molecule involved in the pathogenesis of atherosclerosis and many inflammatory diseases. This study investigates the Hogg1 S326C (rs1052133), CSB–6530C/G (JSNP ID: IMS–JST151339), and E–selectin S149R (rs5361) SNPs in association with AMD. Methods: Genomic DNA was extracted from peripheral blood collected from 88 advanced AMD patients, 110 age–matched controls with no clinical signs of AMD, and 186 random unscreened healthy volunteers. Extracted DNA was then subjected to PCR amplification followed by restriction fragment length digestion. Digested fragments were visualized on ethidium bromide stained polyacrylamide gels for genotyping. Results: The distribution of the Hogg1 S326C, CSB–6530 C/G, and E–selectin S149R SNPs did not differ significantly (p > 0.05, Χ2 test) between the currently available cases of AMD patients and controls. Allele frequency of Hogg1 326C was 20.1% (33/164) in the AMD group as compared to 16.8% (59/352) in the random controls and 24.0% (53/220) in the age–matched controls. Allele frequency of the CSB–6530G was 38.7% (62/160) in AMD cases compared to 36.3% (77/212) in the age–matched controls. For the E–selectin 149R allele frequencies, 9.1% (16/176) was found in AMD cases, 8.9% (33/372) in random controls, and 6.4% (14/220) in age–matched controls (odds ratio of AMD vs age–matched control=1.29, CI: 0.60 to 2.78). Conclusions: The results of our small sample suggest that there is no association between the Hogg1 and CSB–6530C/G SNPs and the genetic risk factors of developing AMD. However, a trend of higher E–selectin 149R was found in AMD cases although it is not statistically significant. Screening larger numbers of AMD cases and age–matched controls is required in order to further analyze the role of E–selectin S149R in this complex disease.
Keywords: age–related macular degeneration • genetics • clinical (human) or epidemiologic studies: risk factor assessment