Association study of complement factor H, C2, CFB, and C3 and age-related macular degeneration in a Han Chinese population.
OBJECTIVE
Genes in the complement pathway, including complement factor H (CFH), C2/BF, and C3, have been reported to be associated with age-related macular degeneration (AMD). Genetic variants, single-nucleotide polymorphisms (SNPs), in these genes were geno-typed for a case-control association study in a mainland Han Chinese population.


METHODS
One hundred and fifty-eight patients with wet AMD, 80 patients with soft drusen, and 220 matched control subjects were recruited among Han Chinese in mainland China. Seven SNPs in CFH and two SNPs in C2, CFB', and C3 were genotyped using the ABI SNaPshot method. A deletion of 84,682 base pairs covering the CFHR1 and CFHR3 genes was detected by direct polymerase chain reaction and gel electrophoresis.


RESULTS
Four SNPs, including rs3753394 (P = 0.0276), rs800292 (P = 0.0266), rs1061170 (P = 0.00514), and rs1329428 (P = 0.0089), in CFH showed a significant association with wet AMD in the cohort of this study. A haplotype containing these four SNPs (CATA) significantly increased protection of wet AMD with a P value of 0.0005 and an odds ratio of 0.29 (95% confidence interval: 0.15-0.60). Unlike in other populations, rs2274700 and rs1410996 did not show a significant association with AMD in the Chinese population of this study. None of the SNPs in CFH showed a significant association with drusen, and none of the SNPs in CFH, C2, CFB, and C3 showed a significant association with either wet AMD or drusen in the cohort of this study. The CFHR1 and CFHR3 deletion was not polymorphic in the Chinese population and was not associated with wet AMD or drusen.


CONCLUSIONS
This study showed that SNPs rs3753394 (P = 0.0276), rs800292 (P = 0.0266), rs1061170 (P = 0.00514), and rs1329428 (P = 0.0089), but not rs7535263, rs1410996, or rs2274700, in CFH were significantly associated with wet AMD in a mainland Han Chinese population. This study showed that CFH was more likely to be AMD susceptibility gene at Chr.1q31 based on the finding that the CFHR1 and CFHR3 deletion was not polymorphic in the cohort of this study, and none of the SNPs that were significantly associated with AMD in a white population in C2, CFB, and C3 genes showed a significant association with AMD.
Center for Human Molecular Biology and Genetics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Sichuan, China.
Xiaoqi
X
Liu
Peiquan
P
Zhao
Shibo
S
Tang
Fang
F
Lu
Jianbin
J
Hu
Chuntao
C
Lei
Xian
X
Yang
Ying
Y
Lin
Shi
S
Ma
Jiyun
J
Yang
Dingding
D
Zhang
Yi
Y
Shi
Tao
T
Li
Yiye
Y
Chen
Yinchuan
Y
Fan
Zhenglin
Z
Yang
D000368:Aged; D044466:Asian People / Q000235:genetics*; D001798:Blood Proteins / Q000235:genetics; D002681:China; D020256:Choroidal Neovascularization / Q000235:genetics; D003175:Complement C2 / Q000235:genetics*; D003176:Complement C3 / Q000235:genetics*; D003180:Complement C3b Inactivator Proteins / Q000235:genetics; D011415:Complement Factor B / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015593:Retinal Drusen / Q000235:genetics; D057135:Wet Macular Degeneration / Q000235:genetics*
D001798:Blood Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003175:Complement C2; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H; D011415:Complement Factor B