Association of Complement Factor H Polymorphisms with Exudative Age-related Macular Degeneration in Ethnic Chinese

¹Tsz Kin Ng, ^1,2Li Jia Chen, ¹Wai Man Chan, ¹Pancy OS Tam, ¹David TL Liu, ^1,2Dennis SC Lam, ^1,2Chi Pui Pang
¹Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China, ²Joint Shantou International Eye Center, Shantou University Medical College, Shantou, China

Age-related macular degeneration (AMD) is the most common form of irreversible blindness in the elderly in developed countries. The complement factor H (CFH) gene, located on chromosome 1q32, which encodes a major inhibitor of the alternative complement pathway, is associated with the risk of developing AMD. Whole CFH gene was screened in Chinese exudative AMD patients to investigate their association. 163 sporadic Chinese patients with exudative AMD and 155 unrelated, age and sex matched control subjects were recruited and their CFH gene, including promoter, exons and intron-exon boundaries, was genotyped by direct sequencing of peripheral blood DNA. Fifty-eight polymorphisms (18 reported and 40 novel) in Hardy-Weinberg equilibrium (HWE) were identified. A major haplotype (T-C-G-G-G-T) constructed by the major alleles of the variants (-257C>T, IVS1-36C>T, V62I, A473A, Q672Q and rs1329428) was detected to confer a 1.63 fold of significantly increased risk for exudatvie AMD (pcorr=0.02, OR=1.63, 95% CI: 1.18-2.23). Two minor haplotypes containing the Y402H or V837I respectively were detected to confer a trend of risk or protective for the disease. Fourteen variants were detected in cases exclusively and eleven were found only in controls. The findings in this study enriched the evidence on the CFH gene as an AMD associated gene and suggested a different polymorphic pattern of CFH in Chinese than in Caucasians. The detection of a major at-risk haplotype and two possible minor AMD associated haplotypes, as well as a group of possible AMD causing/protective rare variants, suggested that CFH has a role in the pathogenesis of exudative AMD in ethnic Chinese.