Dataset Information

Gene-gene interaction of CFH, ARMS2, and ARMS2/HTRA1 on the risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese population.

ABSTRACT: To evaluate the association and interaction of five single-nucleotide polymorphisms (SNPs) in three genes (CFH, ARMS2, and ARMS2/HTRA1) with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in Chinese population.A total of 300 nAMD and 300 PCV patients and 301 normal subjects participated in the present study. The allelic variants of rs800292, rs2274700, rs3750847, rs3793917, and rs1065489 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Gene-gene interactions were evaluated by the data mining approach multifactor-dimensionality reduction (MDR) method.The risk alleles of CFH rs800292, rs2274700, ARMS2 rs3057847, and ARMS2/HTRA1 rs3793917 showed significant difference between nAMD or PCV patients and controls (all P<0.01). The homozygosity of risk alleles for rs800292, rs2274700, rs3750847, and rs3793917 were significantly different between nAMD patients and controls (all P<0.01), and predisposed to PCV patients (all P<0.01). After cross-validation consistency (CVC) and permutation tests, the two-locus model rs2274700_rs3750847 has a balanced accuracy of 64.37% in predicting nAMD disease risk. The one-marker model, rs3750847, and two-locus model rs2274700_rs3750847 has a balanced accuracy of 66.07% and 65.89% in predicting PCV disease risk, respectively. Furthermore, CFH rs1065489 did not show significant association with nAMD (P>0.01), but was strongly associated with PCV in Chinese patients (P<0.001).In this study, we found that the interaction of ARMS2 and ARMS2/HTRA1 is significantly associated with nAMD, and the interaction of CFH and ARMS2 is pronounced in PCV development in Chinese population.

SUBMITTER: Huang L

PROVIDER: S-EPMC4429281 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gene-gene interaction of CFH, ARMS2, and ARMS2/HTRA1 on the risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese population.

Huang L L Meng Q Q Zhang C C Sun Y Y Bai Y Y Li S S Deng X X Wang B B Yu W W Zhao M M Li X X

Eye (London, England) 20150313 5

<h4>Purpose</h4>To evaluate the association and interaction of five single-nucleotide polymorphisms (SNPs) in three genes (CFH, ARMS2, and ARMS2/HTRA1) with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in Chinese population.<h4>Methods</h4>A total of 300 nAMD and 300 PCV patients and 301 normal subjects participated in the present study. The allelic variants of rs800292, rs2274700, rs3750847, rs3793917, and rs1065489 were determined by matrix-as ...[more]

PMID: 25771815

Similar Datasets

Project description:PurposeA nonsynonymous coding variant in the manganese superoxide dismutase (SOD2) gene (V16A, rs4880) has been implicated in neovascular age-related macular degeneration (AMD). However, the findings have been inconsistent. Two studies in Japanese populations reported an opposite direction of association of the same allele at the V16A variant, whereas one study in a Northern Irish population found no effect of the variant on the risk of developing neovascular AMD. To address these apparently contradictory reports, we validated the association in a Japanese population.MethodsIn a Japanese population, we genotyped the V16A variant in 116 neovascular AMD patients, 140 polypoidal choroidal vasculopathy (PCV) patients, and 189 control participants. This association was also tested in a population of PCV participants to avoid variable findings across studies due to underlying sample heterogeneity and because disease phenotype was not well described in previous studies. We analyzed a tagging single nucleotide polymorphism (SNP) in addition to the V16A variant to capture all common SOD2 variations verified by the HapMap project. Genotyping was conducted using TaqMan technology. Associations were tested using single-SNP and haplotype analyses as well as a meta-analysis of the published literature. Population stratification was also evaluated in our study population.ResultsWe found no detectable association of the V16A variant or any other common SOD2 variation with either neovascular AMD or PCV, as demonstrated by both single-SNP and haplotype analyses. Population structure analyses precluded stratification artifacts in our study cohort. A meta-analysis of the association between the V16A variant and neovascular AMD also failed to detect a significant association.ConclusionsWe found no evidence to support the role of any common SOD2 variations including the V16A variant in the susceptibility to neovascular AMD or PCV. Our study highlights the importance and difficulty in replicating genetic association studies of complex human diseases.

Project description:PURPOSE: Using a candidate-gene approach, a recent case-control study identified a previously unknown association between neovascular age-related macular degeneration (AMD) and the coding Met72Thr variant in the pigment epithelium-derived factor (PEDF) gene in a Taiwan Chinese population. However, a subsequent replication study failed to see this association in a white European population. We noted an important difference in the sample ascertainment scheme between these two studies. The original study did not consider findings of indocyanine green (ICG) angiography for disease classification, which is the only way to obtain a clear image of polypoidal choroidal vasculopathy (PCV) lesions. This suggests that their cohort might include a considerable amount of PCV, given its high prevalence in the Chinese population. In contrast, the replication study intentionally excluded PCV from the case cohort on the basis of ICG angiograms. Therefore, the inconsistent finding might be caused by potential sample heterogeneity between these two studies. In this respect, this association needed to be examined in a case series of clearly defined individuals with neovascular AMD and PCV. The aim of this study was to validate the previously reported association of the PEDF Met72Thr variant in a well characterized Japanese population with neovascular AMD and PCV. METHODS: We genotyped the Met72Thr variant (rs1136287) in 116 patients with neovascular AMD, 140 patients with PCV, and 189 control participants in a Japanese population. Genotyping was performed using TaqMan technology. We tested for an association of this variant with neovascular AMD and PCV separately. We also evaluated population stratification in our study cohort. RESULTS: We found no statistically significant evidence for association between rs1136287 and either neovascular AMD or PCV under any genetic models (trend, genotypic, dominant, and recessive genetic models; p>0.05). Population structure analyses excluded stratification artifact in our study population. CONCLUSIONS: We report a lack of association between the PEDF Met72Thr variant and either neovascular AMD or PCV in a Japanese population. We conclude that the Met72Thr variant does not play a significant role in the risk of developing neovascular AMD or PCV.

Dataset Information

Gene-gene interaction of CFH, ARMS2, and ARMS2/HTRA1 on the risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese population.

Publications

Gene-gene interaction of CFH, ARMS2, and ARMS2/HTRA1 on the risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets