HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: iovs.08-2275v1 50/2/533    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by McKay, G. J. Articles by Hughes, A. E. Search for Related Content PubMed PubMed Citation Articles by McKay, G. J. Articles by Hughes, A. E.

Further Assessment of the Complement Component 2 and Factor B Region Associated with Age-Related Macular Degeneration

¹From the Centre for Vision Sciences and the ²Centre for Public Health, Queen’s University of Belfast, Belfast, Northern Ireland, United Kingdom.

PURPOSE. Polymorphic variation in genes involved in regulation of the complement system has been implicated as a major cause of genetic risk, in addition to the LOC387715/HTRA1 locus and other environmental influences. Previous studies have identified polymorphisms in the complement component 2 (CC2) and factor B (CFB) genes, as potential functional variants associated with AMD, in particular CFB R32Q and CC2 rs547154, both of which share strong linkage disequilibrium (LD).

METHODS. Data derived from the HapMap Project were used to select 18 haplotype-tagging SNPs across the extended CC2/CFB region for genotyping, to measure the strength of LD in 318 patients with neovascular AMD and 243 age-matched control subjects to identify additional potential functional variants in addition to those originally reported.

RESULTS. Strong LD was measured across this region as far as the superkiller viralicidic activity 2–like gene (SKIV2L). Nine SNPs were identified to be significantly associated with the genetic effect observed at this locus. Of these, a nonsynonymous coding variant SKIV2L R151Q (rs438999; OR, 0.48; 95% confidence interval [CI], 0.31–0.74; P < 0.001), was in strong LD with CFB R32Q, rs641153 (r² = 0.95) and may exert a functional effect. When assessed within a logistic regression model measuring the effects of genetic variation at the CFH and LOC387715/HTRA1 loci and smoking, the effect remained significant (OR, 0.38; 95% CI, 0.22–0.65; P < 0.001). Additional variation identified within this region may also confer a weaker but independent effect and implicate additional genes within the pathogenesis of AMD.

CONCLUSIONS. Because of the high level of LD within the extended CC2/CFB region, variation within SKIV2L may exert a functional effect in AMD.

This article has been cited by other articles:

				E. Kortvely, S. M. Hauck, G. Duetsch, C. J. Gloeckner, E. Kremmer, C. S. Alge-Priglinger, C. A. Deeg, and M. Ueffing ARMS2 Is a Constituent of the Extracellular Matrix Providing a Link between Familial and Sporadic Age-Related Macular Degenerations Invest. Ophthalmol. Vis. Sci., January 1, 2010; 51(1): 79 - 88. [Abstract] [Full Text] [PDF]

				I. Kaur, S. Katta, R. K. Reddy, R. Narayanan, A. Mathai, A. B. Majji, and S. Chakrabarti The Involvement of Complement Factor B and Complement Component C2 in an Indian Cohort with Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., January 1, 2010; 51(1): 59 - 63. [Abstract] [Full Text] [PDF]