Complement factor H polymorphisms in Japanese population with age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is the leading cause of visual disability in the elderly in developed countries or in those with a predominant Caucasian population. The disease is characterized by poor vision in the central field due to a progressive destruction of the macular area. A hallmark of the early stage of AMD is the development of drusen, a complex mixture of proteins and cellular deposits, which accumulate between the retinal pigment epithelium (RPE) and Bruch's membrane. Recent studies have shown that drusen are composed of proteins related to activated complement and suppressor Recently, five studies reported that a tyrosine to histidine change at amino acid 402 (Y402H has a T to C substitution at nucleotide 1277 in exon 9) of the complement factor H (CFH) gene was strongly associated with AMD The CFH gene, located on chromosome 1q32, was the first of 13 distinct loci mapped on 11 chromosomes to be identified as being associated with AMD The purpose of this study was to analyze the five haplotypes previously identified in the CFH gene in a Japanese population with exudative AMD and in age-matched controls. METHODS Age-related macular degeneration patients and age-matched controls: Blood samples were collected from 96 Japanese patients with exudative (wet type) AMD and 89 age-matched controls between 50-85 years old. AMD was diagnosed by ophthalmoscopic and fluorescein angiographic findings. In controls, no signs of early AMD, such as soft drusen or irregular pigmentations of the RPE in the macular area, were observed ophthalmoscopically. Informed consent was obtained from all participants, and the procedures used conformed to the tenets of the Declaration of Helsinki. Purpose: To study the frequency of five haplotypes previously reported in the complement factor H (CFH) gene for Japanese patients with age-related macular degeneration (AMD). Methods: Genomic DNA was isolated from peripheral blood samples taken from 96 Japanese AMD patients and 89 agematched controls. All patients were diagnosed as having exudative (wet-type) AMD. The amplified polymerase chain reaction (PCR) products of CFH exons 2, 9, and 13, and intron 6 were analyzed by temperature gradient capillary electrophoresis (TGCE) and by direct sequencing. The haplotypes were identified, and their frequencies were calculated and compared with reported results. Results: Five haplotypes were identified in the Japanese population including four already reported in the American population. The frequencies of these haplotypes were significantly different between Japanese and American in both control and case groups. The haplotype containing Y402H, which was previously reported to be associated with AMD, was only 4% in the control and case population, with a p value of 0.802. However, two other haplotypes were found as risk factors, which gave an increased likelihood of AMD of 1.9 and 2.5 fold (95% CI 1.12-3.69 and 1.42-6.38). One protective haplotype that decreased the likelihood of AMD by 1.6 fold (95% CI 0.26-0.67) was identified. Conclusions: The frequencies for five haplotypes previously identified were analyzed in a Japanese population with AMD. Four previously found haplotypes were identified and one additional haplotype was found. The frequencies of each haplotype were significantly different from that in found Americans affected with AMD. Two of the haplotypes were identified as risk factors and one was considered protective

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