Significance of C2/CFB variants in age-related macular degeneration and polypoidal choroidal vasculopathy in a Japanese population.
OBJECTIVE
To determine whether genetic variants in the complement component 2 and factor B gene (C2/CFB) locus are associated with the risk for typical age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV) in a Japanese population.


METHODS
Four single nucleotide polymorphisms (SNPs) were genotyped across the C2/CFB locus of patients with typical AMD (n = 455) or PCV (n = 581) and of 865 controls. Differences in the observed genotypic distribution between the case and control groups were tested by logistic regression analysis for age and sex adjustments. Significant associations were confirmed using a second control group of 336 cataract patients. A further model adjusting for age-related maculopathy susceptibility 2 (ARMS2) A69S, complement factor H (CFH) I62V, age, sex and smoking status was performed, to confirm their independent association from other covariates.


RESULTS
C2 rs547154 and CFB rs541862 were significantly associated with typical AMD and PCV in this Japanese sample (P < 0.05). These two SNPs were also significantly associated with typical AMD and PCV in evaluation of the second control cohort (P < 0.05). Furthermore, an independent association of C2/CFB variants was found for both typical AMD and PCV with age, sex, smoking, and genetic background of ARMS2 A69S and CFH I62V (vs. typical AMD: P = 0.0073, odds ratio [OR] = 0.47; vs. PCV: P = 0.0083, OR = 0.53).


CONCLUSIONS
C2/CFB variants play a protective role in the risk of developing neovascular AMD and PCV in the Japanese.
Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Isao
I
Nakata
Kenji
K
Yamashiro
Ryo
R
Yamada
Norimoto
N
Gotoh
Hideo
H
Nakanishi
Hisako
H
Hayashi
Yumiko
Y
Akagi-Kurashige
Akitaka
A
Tsujikawa
Atsushi
A
Otani
Masaaki
M
Saito
Tomohiro
T
Iida
Akio
A
Oishi
Keitaro
K
Matsuo
Kazuo
K
Tajima
Fumihiko
F
Matsuda
Nagahisa
N
Yoshimura
D000368:Aged; D002829:Choroid / Q000098:blood supply*; D020256:Choroidal Neovascularization / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D003175:Complement C2 / Q000235:genetics* / Q000378:metabolism; D011415:Complement Factor B / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
D003175:Complement C2; D004247:DNA; D011415:Complement Factor B