Analysis of variants in the complement factor H, the elongationof very long chain fatty acids-like 4 and the hemicentin 1 genes ofage-related macular degeneration in the Finnish population

[摘要] Purpose: A strong association of a Tyr402His polymorphism in thecomplement factor H (CFH) gene and a Met299Val polymorphism in theelongation of very long chain fatty acids-like 4 (ELOVL4) gene withage-related macular degeneration (AMD) has been identified in Caucasianpopulations in the United States. Earlier a Gln5345Arg variant in thehemicentin 1 (HMCN1) gene was reported in a large AMD family in theUnited States. We wanted to investigate whether the polymorphisms of theCFH and the ELOVL4 genes or the mutation of the HMCN1 gene areassociated with AMD in patients originating from the Finnish populationwith characteristics of a genetic isolate.Methods: The material consisted of familial (n=181) and sporadiccases (n=154) with AMD, a control group with no AMD (non-AMD controls,n=105), and a control group of anonymous blood donors (blood donorcontrols, n =350). The DNA of the subjects was sequenced to analyze thevariants of the three genes.Results: We detected a strong association between the C/C-genotypecompared to the T/T-genotype of Tyr402His polymorphism (first base ofthe Tyr-codon changes) of the CFH gene and AMD in the AMD cases comparedto the non-AMD (p=8.86x10-12) or to blood donor controls(p=2.02x10-13). The frequency of the C/C genotype wassignificantly increased in both familial cases compared to non-AMDcontrols with non-adjusted odds ratio (OR) 10.1 (confidence intervals[CI] 95% 4.64-22.2) or compared to blood donor controls withnon-adjusted OR 5.50 (CI 95% 3.17-9.55) and in sporadic cases withnon-adjusted OR 9.33 (CI 95% 4.10-21.3; non-AMD-controls), OR 5.06 (CI95% 2.75-9.28; blood donor controls). Frequency of C allele differedsignificantly between cases and controls (p=1.32x10-11;non-AMD-controls and p=3.94x10-14; blood donor controls). Noassociation with AMD was detected with Met299Val polymorphism in theELOVL4 gene in the familial or sporadic cases compared to non-AMD orblood donor controls. None of our subjects (258 AMD cases, 72 non-AMDcontrols) had the Gln5345Arg variant in the HMCN1 gene.Conclusions: The CFH gene polymorphism seems to be an importantetiologic factor for AMD also in the isolated Finnish population.

[学科分类] 生物化学/生物物理