Susceptibility genes and progression in age-related maculopathy: a study of single eyes.

PURPOSE: The specific role of single-nucleotide polymorphisms (SNPs) in the progression of age-related maculopathy (AMD) is not clearly understood. The present study was conducted to investigated whether variants in three susceptibility genes are differentially associated with progression to early and late AMD. METHODS: The Münster Ageing and Retina Study (MARS) cohort includes 722 patients with different stages of AMD. Participants were reexamined after a median of 2.6 years. The association of SNPs in the CFH, ARMS2, and C3 genes with AMD progression was evaluated in 1435 single eyes by using multivariate logistic regression models with generalized estimating equations. RESULTS: CFH-rs1061170 was significantly related to the development of early (OR = 1.94, 95% confidence interval [CI], 1.3-3.0 for heterozygous, and OR = 2.9 [95% CI, 1.7-5.1] for homozygous allele carriers) but not to late AMD. In contrast, ARMS2-rs10490924 was associated only with progression to advanced disease (OR = 1.2 [0.7-2.1] and OR = 2.1 [1.1-3.9], respectively). The variant C3-rs2230199 showed no relation with AMD progression. CONCLUSIONS: The findings indicate that AMD progression is differentially affected by genotypic variants. Probably, aging processes of the human retina predispose to AMD onset in the presence of genetic variation in the complement system, which alters immunoregulatory and inflammatory responses. The specific functional role of ARMS2-rs10490924 remains as yet unknown, but it appears to mainly affect the progression to late AMD stages.

LOC387715, smoking and their prognostic impact on visual functional status in age-related macular degeneration-The Muenster Aging and Retina Study (MARS) cohort.

PURPOSE: To prospectively evaluate the impact of homozygosity in the A69S-SNP of the LOC387715-gene, smoking history, and their interaction on visual functional status (v-FS) in age-related macular degeneration (AMD). METHODS: The Muenster Aging and Retina Study (MARS) cohort (n = 656; 58.8% women, mean age 70.2 years) was followed over a mean of 2.5 years. AMD-status, genotype and smoking history were assessed at baseline. V-FS [from 0 (low) to 100 (unimpaired) points in general-, near- and far-vision], were AMD-status assessed at baseline and at follow-up. Linear models with stepwise adjustments for covariates were used to analyze decline of v-FS over time. RESULTS: In initial models, homozygosity for the A69S-variant was negatively associated with all three dimensions of the v-FS. After including smoking history, ever smoking was negatively associated with declines in near and far vision (-4.82 and -5.12 points, respectively; each p < 0.05). In smokers homozygous for the A69S-variant the number of cigarettes smoked per day (smoking intensity) was negatively associated with all three dimensions of the v-FS (interaction term each p < 0.05). Time since smoking cessation in former smokers protected against declines in near and far vision. These effects were independent of the AMD-status at baseline. CONCLUSIONS: The interaction of homozygosity for the A69S-variant and smoking intensity had a negative impact on general-, near-, and far visual functional status independent of AMD-status. Quitting smoking seemed to have a time-dependent protective effect on near and far vision.

Automated scanning for phylogenetically informative transposed elements in rodents.

Transposed elements constitute an attractive, useful source of phylogenetic markers to elucidate the evolutionary history of their hosts. Frequent and successive amplifications over evolutionary time are important requirements for utilizing their presence or absence as landmarks of evolution. Although transposed elements are well distributed in rodent taxa, the generally high degree of genomic sequence divergence among species complicates our access to presence/absence data. With this in mind we developed a novel, high-throughput computational strategy, called CPAL (Conserved Presence/Absence Locus-finder), to identify genome-wide distributed, phylogenetically informative transposed elements flanked by highly conserved regions. From a total of 232 extracted chromosomal mouse loci we randomly selected 14 of these plus 2 others from previous test screens and attempted to amplify them via PCR in representative rodent species. All loci were amplifiable and ultimately contributed 31 phylogenetically informative markers distributed throughout the major groups of Rodentia.