Association Analysis of CFH, C2, BF, and HTRA1 Gene Polymorphisms in Chinese Patients with Polypoidal Choroidal Vasculopathy

• Published in: Investigative ophthalmology & visual science Vol. 49; no. 6; pp. 2613 - 2619
• Main Authors: Lee, Kelvin Y, Vithana, Eranga N, Mathur, Ranjana, Yong, Victor H, Yeo, Ian Y, Thalamuthu, Anbupalam, Lee, Mun-Wai, Koh, Adrian H, Lim, Marcus C, How, Alicia C, Wong, Doric W, Aung, Tin
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.06.2008; Association for Research in Vision and Ophtalmology
• Subjects: Adult; Aged; Aged, 80 and over; Asian People - genetics; Biological and medical sciences; Choroid - blood supply; Choroid Diseases - genetics; Complement C2 - genetics; Complement Factor B - genetics; Complement Factor H - genetics; Eye and associated structures. Visual pathways and centers. Vision; Female; Fluorescein Angiography; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genotype; Haplotypes; High-Temperature Requirement A Serine Peptidase 1; Humans; Linkage Disequilibrium; Macular Degeneration - genetics; Male; Medical sciences; Middle Aged; Ophthalmology; Peripheral Vascular Diseases - genetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Risk Factors; Serine Endopeptidases - genetics; Singapore - epidemiology; Vertebrates: nervous system and sense organs; Singapore; Human; Polypoidal choroidal vasculopathy; Association; Gene; Analysis; Chinese; Ophthalmology; Polymorphism
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.07-0860

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. 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. 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. The SNPs rs3753394 and rs800292 of CFH and rs11200638 of HTRA1 are significantly associated with the risk of PCV in Chinese patients.