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G. J. Pauer, G. M. Sturgill, N. S. Peachey, S. A. Hagstrom, Clinical Genomic and Proteomic AMD Study Group; Analysis of Complement Component 2 (C2) and Factor B (BF) Variants in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1662.
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Several single nucleotide polymorphisms (SNPs) in the C2 and BF genes have been linked with age-related macular degeneration (AMD). To validate these associations in independent case - control Caucasian data sets, we genotyped SNPs in C2 and BF.
Genotyping was performed on two SNPs in C2 (rs547154 [IVS10] and rs9332739 [E318D]) and three SNPs in BF (rs4151667 [L9H], rs641153 (R32Q), and rs12614 (R32W)]. Two separate cohorts were evaluated including 876 clinically well characterized patients with AMD and 598 unaffected control subjects from the Cole Eye Institute (CEI) and 298 patients and 649 controls from the Cleveland VA Medical Center (VA). The chi-square test was used for comparisons of categorical variables and allele and genotype frequencies and to check for Hardy-Weinberg equilibrium. P values <0.05 were defined as nominally significant and were further subjected to Bonferroni correction to account for multiple comparisons testing.
As previously reported, a significant protective association with AMD was indicated for two of the analyzed SNPs, rs547154 in the C2 gene (P < 0.0001 ) and rs641153 in the BF gene (P < 0.0001) in all stages of AMD combined. Interestingly, a novel protective effect was indicated for a third SNP, rs12614 (R32W) in BF (P < 0.001). These protective associations remained, except for rs12614 in the VA cohort, following a conservative Bonferroni correction. No association with AMD was found for SNPs rs9332739 (E318D) in C2 or rs4151667 (L9H) in BF.
This study provides validation on the association of rs547154 (C2) and rs641153 (BF) SNPs with a reduced risk of AMD in two separate Caucasian cohorts. An additional protective variation, rs12614 (BF) may also confer a protective effect. Although the E318D and L9H variants have shown association with AMD in previous studies, this was not replicated here, indicating that these SNPs may have less predictive value.
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