Further assessment of the complement component 2 and factor B region associated with age-related macular degeneration.

Authors:
Dr Ruth Hogg, ATCL (Solo Piano) BSc(Hons) Optometry, MCOptom,  PhD
Dr Ruth Hogg, ATCL (Solo Piano) BSc(Hons) Optometry, MCOptom, PhD
Centre for Public Health, Queen's University Belfast
Senior Lecturer
Ophthalmology, age-related macular degeneration, diabetic retinopathy, visual psychophysics, epidemiology, nutrition
Belfast, Northern Ireland | United Kingdom

Invest Ophthalmol Vis Sci 2009 Feb 20;50(2):533-9. Epub 2008 Sep 20.

Centre for Vision Sciences, 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 (r(2)=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.

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http://dx.doi.org/10.1167/iovs.08-2275DOI Listing
February 2009
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