Gender specific association of a complement component 3 polymorphism with polypoidal choroidal vasculopathy.
Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of irreversible blindness in developed countries. In this study, we investigated the associations of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement component 3 (C3) gene with both neovascular AMD and PCV, and potential epistatic effects on C3. Eight tagging SNPs in C3 were genotyped in 708 unrelated study subjects: 200 neovascular AMD patients, 233 PCV patients and 275 controls. Among the eight C3 SNPs, rs17030 was associated with PCV after adjusted for gender and SNP-gender interaction (P = 0.008, OR = 2.94; 95% CI: 1.32-6.52). Moreover, an interaction between rs17030 and gender was identified in PCV (P = 0.02). After stratification by gender, the rs17030 G allele was found to confer an increased risk for PCV in male (P = 0.010, OR = 1.56) but not in female. The haplotype AG defined by the major alleles of rs17030 and rs344555 was also associated with PCV in male (P = 0.010, OR = 0.64). In contrast to PCV, none of the eight SNPs was significantly associated with neovascular AMD. This study shows an association of C3 rs17030 with PCV in male, indicating that C3 may have an epistatic effect with gender in the pathogenesis of PCV.
1] Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China [2] Shenzhen Eye Hospital, Shenzhen, China.
Ke
K
Liu
Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
Timothy Y Y
TY
Lai
Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
Sylvia W Y
SW
Chiang
Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China.
Vesta C K
VC
Chan
Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China.
Alvin L
AL
Young
Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
Pancy O S
PO
Tam
Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
Chi Pui
CP
Pang
1] Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China [2] Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China.
Li Jia
LJ
Chen
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D002681:China; D002829:Choroid / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D020256:Choroidal Neovascularization / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D003176:Complement C3 / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors
D003176:Complement C3