The Study Of Mutation In The Complement Factor H Gene Associated With Age-related Macular Degeneration

Purpose: Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly population in the developed world. Due to the growing elderly population, the prevalence of AMD is expected to rise. Two subgroups of AMD are classically distinguished: dry and wet.. While the etiology of AMD remains unclear, now it is generally considered to be a multifactorial disease, with environmental and polygenic components. Smoking and age are generally accepted risk factors but inflammation, hypertension, and dietary fats have also been shown to associate with increased risk for AMD. A genetic predisposition has been suggested, based on familial aggregation and twins studies. Molecular biology studies have demonstrated or suggested a role for some gene in AMD, for example hemicentin-1(HMCN1)gene, the apolipoprotein E (APOE) gene and ABCA4 gene. A lot of study demonstrated that a tyrosine to histidine chage at amino acid 402(Y402H has a T to C substitution at nucleotide 1277 in exon 9) of the complement factor H gene was strongly associated with AMD, but not yet in Chinese population. CFH is a component of the immune system which helps to regulate the body's inflammatory response by protecting against uncontrolled complement activation. Our purpose is to investigate this association between the CFH gene and AMD in the southeast of Liaoning province in China using a case-control study.Methods: Twenty-five cases of wet form AMD patients, fourteen cases of dry form AMD patients were selected, including 15 male cases and 24 female cases, mean age is 68.0±7.9, and compared with fifty-one age-matched controls, including 20 male cases and 31 female cases, mean age is 67.0±5.7. Genomic DNA was extracted from peripheral blood samples. The ninth exonof CFH gene was amplified by polymerase chain reaction (PCR) and analyzed by single strand conformation polymorphism (SSCP) assay, The position and type of CFH gene mutation were determined by direct sequencing. The association between gene mutation and AMD was studied by statistical analysis.Results: T→C mutation at 1277 in the complement factor H gene results in a tyrosine to histidine change at codon 402 ( Y402H ), It is missense mutation. It is found in 7 cases of case group, but in 2 cases of contrast group,χ~2=4.832, P<0.05. OR=5.359,95%CI is 1.047-27.446. There is statistical difference between case group and contrast group. Thus there is association between the complement factor H (CFH) gene and AMD patients in the southeast of Liaoning province in China .Conclusions: These results suggest a significant association between the CFH gene and AMD in the southeast of Liaoning province in China. This relationship with the CFH may lead to new strategies for prevention and treatment of AMD.