Association analysis of CFH, C2, BF, and HTRA1 gene polymorphisms in Chinese patients with polypoidal choroidal vasculopathy.
OBJECTIVE
Polypoidal choroidal vasculopathy (PCV) is a major cause of serosanguinous maculopathy in Chinese patients with age-related macular degeneration (AMD). Variants in the CFH and HTRA1/LOC387715 genes are strongly associated with AMD in Caucasians and Chinese. Variants in the C2 and BF genes have been found to confer a significantly reduced risk of AMD. This study was undertaken to determine whether these associations occur in Chinese patients with PCV.


METHODS
Patients of Chinese ethnicity with clinically and angiographically diagnosed PCV and normal control subjects were recruited from the Singapore National Eye Centre. Five single-nucleotide polymorphisms (SNPs) in the CFH gene, two each within the C2 and BF genes and two variants located in the LOC387715 and HTRA1 genes, were screened in all patients and control subjects.


RESULTS
Seventy-two patients with PCV and 93 normal control subjects were studied. A significant association was noted with CFH variants rs3753394 and rs800292 among the PCV cases (P = 0.0015 and P = 0.0045, respectively). Individuals homozygous for the TT genotype of rs3753394 had a significantly higher risk (P = 0.0076) of PCV (OR = 4.29; 95% CI: 1.47-12.50) than those carrying a single copy of the T allele (P = 0.3210; OR = 1.69; 95% CI: 0.60-4.78), after adjustment for such risk factors as age and sex. The genotype frequencies of rs11200638 and rs10490924 in HTRA1 and LOC387715, respectively, were also found to be significantly different between patients with PCV and normal control subjects (P = 0.00032 and P = 0.003, respectively). The AA genotype of rs11200638 and TT genotype of rs10490924 conferred a 4.9-fold (95% CI: 1.85-12.95) and 4.89-fold (95% CI: 1.85-12.90) increased risk of PCV, respectively, after adjustment for age and sex. The Y402H variant of CFH (rs1061170) and the BF and C2 variants were not significantly different in patients and normal control subjects.


CONCLUSIONS
The SNPs rs3753394 and rs800292 of CFH and rs11200638 of HTRA1 are significantly associated with the risk of PCV in Chinese patients.
Lee
Kelvin Y
KY
Singapore National Eye Centre, Singapore.
Vithana
Eranga N
EN
Mathur
Ranjana
R
Yong
Victor H
VH
Yeo
Ian Y
IY
Thalamuthu
Anbupalam
A
Lee
Mun-Wai
MW
Koh
Adrian H
AH
Lim
Marcus C
MC
How
Alicia C
AC
Wong
Doric W
DW
Aung
Tin
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002829:Choroid / Q000098:blood supply; D015862:Choroid Diseases / Q000235:genetics*; D003175:Complement C2 / Q000235:genetics*; D011415:Complement Factor B / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics*; D012846:Singapore / Q000453:epidemiology
C493495:CFH protein, human; D003175:Complement C2; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases; D011415:Complement Factor B