degeneration in Han Chinese confer risk to exudative age-related macular CX 3 CR 1 and HTRA 1 , CFH Polymorphisms in

Background/Aims Single nucleotide polymorphisms (SNPs) in Complement Factor H (CFH), HTRA1 and CX3CR1 are associated with age-related macular degeneration (AMD) in Caucasian population. We aimed to determine whether, and of what magnitude, these AMD susceptibility SNPs are associated with exudative AMD in Han Chinese. Methods Exudative AMD cases and age-matched controls were recruited from Nantong University Hospital (109 cases, 150 controls). Six SNPs in CFH, HTRA1 and CX3CR1 were genotyped. The allele/genotype frequencies were compared between the case and the control. Interactions of SNPeSNP or SNPesmoking status were assessed. Results The CFH rs800292 showed significant associations with a reduced risk for exudative AMD. CX3CR1 V249I and T280M and the HTRA1 promoter SNP were significantly associated with the risk of exudative AMD. The two SNPs in CX3CR1 were in complete linkage disequilibrium. None of the AMD-susceptibility SNPs had interactions with each other or with smoking status to confer an altered AMD risk. Conclusions We have replicated the associations of the CFH and HTRA1 SNPs and report for the first time the association of CX3CR1 with exudative AMD in Han Chinese. There was no interaction among the SNPs from different genes, indicating that they might alter the AMD risk independently. INTRODUCTION Age-related macular degeneration (AMD) is a lateonset disorder characterised by progressive degeneration of a central region in the retina. AMD is a common eye disease estimated to affect approximately 50 million worldwide and is the leading cause of vision loss in elderly in the industrialised countries. Because of the rapid expansion of the elderly population in mainland China, the prevalence of AMD has become one of the major threats to the life quality of this group of people. A population-based study in Beijing in 2006 unveiled that AMD contributed to 9.7% of visual impairment and blindness in elderly residents in Beijing. A population-based study on 2045 elderly residents of Chinese population in Taiwan also reported that AMD contributed to 10.4% of cases of low vision or blindness. AMD is a complex disease with multiple genetic and environmental risk factors. Many efforts have been made to identify AMD-associated single nucleotide polymorphisms (SNPs) that can be used to predict the likelihood of disease onset and provide information on the disease-causing molecules. Several AMD-susceptibility SNPs such as those in Complement Factor H (CFH), LOC387715/ HtrA1/PLEKHA1 loci and CX3CR1 6 have been discovered. However, most of those studies were conducted on populations of European descent. Ethnic determinants of AMD susceptibility have been well documented. Interestingly, Asian population was reported to exhibit different phenotypical expression of AMD from European-descent population. 9 Therefore, it is possible that an allele that confers risk in one ethnic group might confer different levels of or no risk in another group. It is at least partially due to the obviously different distribution of gene variations among ethnic groups. For example, NCBI Reference Assembly recorded that the allele frequency of CFH Y402H (rs1061170) is 28.2% in European descent but only 6.7% in Han Chinese, and the allele frequency of CX3CR1V249I (rs3732379) is 18.8% in European descent and 4.2% in Han Chinese. The association of the CFH Y402H variant with AMD has been replicated independently in populations of European descent. However, several studies on Japanese population failed to replicate the association. Although there is a report demonstrating the association of the CFH Y402H variant with AMD in a Taiwan Chinese population, it remains controversial because a study on Hong Kong Chinese population failed to replicate the association. The persisting uncertainties may result in part from a low allele frequency of the CFH Y402H variant in Asian populations. Because of distinct distribution of genetic variations among ethnic groups, these AMD-susceptibility SNPs discovered in European-descent population need to be tested in other ethnic groups. In this study, we recruited AMD and age-matched controls from the Nantong area of Eastern China and selected the SNPs that were consistently reported to be associated with AMD in independent studies. Among those candidates were three SNPs in CFH, two SNPs in CX3CR1 and one SNP in HTRA1. METHODS Subjects The study was approved by the ethics committee of the Nantong University, and all procedures were conducted in accordance with the principles of the Declaration of Helsinki. Each participant signed the informed consent form approved by the ethics committee of the Nantong University and was fully informed of the purpose of and the procedures involved in the study. Department of Ophthalmology, the Affiliated Hospital of Nantong University, Nantong, China Correspondence to Huaijin Guan, Department of Ophthalmology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, China; gtnantongeye@gmail.com Xiaozhao Yang works as a resident in the Eye Research Institute, Xi’an No. 1 Hospital, China. Accepted 20 December 2009 Published Online First 10 June 2010 Br J Ophthalmol 2010;94:1211e1214. doi:10.1136/bjo.2009. 165811 1211 Clinical science group.bmj. com on September 10, 2010 Published by bjo.bmj. com Downloaded from