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K. Park, N. Tosakulwong, E. Ryu, A. O. Edwards; Candidate Gene Studies in Complement and Immune Regulatory Genes: Re-assessment of SERPING1, CX3CR1, and Identification of Novel Variants Associated With Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3443.
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Genetic variation in genes encoding complement components including CFH, C2/BF, and C3 has shown strong association with age-related macular degeneration (AMD). Recently, variation in the complement component 1 inhibitor gene (SERPING1) was reported to decrease the risk of developing (AMD). This study was performed to replicate the association between SERPING1 and AMD, to re-assess CX3CR1, and to evaluate the effect of genetic variants in candidate genes encoding complement components and inflammatory proteins on AMD risk.
Seven SNPs tagging common haplotypes across SERPING1 were genotyped on 738 Mayo subjects and the association with AMD studied using single SNP and haplotype association analyses. The SNP in intron 6 (rs2511989) previously reported to increase the risk of AMD was studied in an additional 1,541 subjects from the age-related eye disease study (AREDS). Seventy two SNPs across18 loci representing complement component genes (C4BPA, C4BPB and C5-9), cardiovascular risk loci (CDKN2B and LOC72998), and inflammatory or immunity genes (IL1A, IL10, IL18, IFNG, CCL2, TGFB1, SERPINF1, CX3CR1 and RANTES) were also genotyped on the Mayo subjects.
The SNPs in SERPING1 were not associated with AMD in the Mayo subjects (P=0.13-0.70) including rs2511989 which also was not associated with AMD in the AREDS subjects (P=0.45). Evaluation of haplotypes across SERPING1 did not reveal association with AMD and single SNPs were not associated with AMD subtypes (early, geographic atrophy, exudation). A previously reported variant (T280M) in CX3CR1 was also not associated with AMD. While genetic variation in most of the candidate genes (C4BPA, C4BPB, C5, C6, C7, C9, CDKN2B, LOC72998 IL1A, IL10, IL18, CCL2, TGFB1, SERPINF1, and RANTES)was not associated with AMD (P=0.09-0.96), SNPs in C8A (P=0.02 and 0.07), C8B (P=0.01) and IFNG (P=0.007-0.048) were marginally associated with AMD in the Mayo subjects.
We were unable to replicate the previously reported association between AMD and SERPING1 or CX3CR1. Novel variation associated with AMD was observed in 3 genes, represented the common terminal complement pathway and immune regulation.
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