Dataset Information

Association of rs6982567 near GDF6 with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Han Chinese cohort.

ABSTRACT:

Background

Growth differentiation factor 6 (GDF6) has been reported to be a novel disease gene for age-related macular degeneration (AMD) in Caucasians. This study aimed to investigate whether rs6982567 was associated with neovascular AMD (nAMD) or polypoidal choroidal vasculopathy (PCV) in a Han Chinese cohort.

Methods

A total of 612 participants (251 PCV patients, 157 nAMD patients and 204 controls) were included in this study. The SNaPshot system was used to genotype the rs6982567. PLINK software was used to evaluate the genotypes and allele frequencies of patients and controls.

Results

The allele frequencies of rs6982567 were not significantly associated with nAMD, PCV or PCV and nAMD combined. Subjects with the TT genotype had a 2.42-fold greater risk of PCV (95% confidence interval, 1.07-5.43, p = 0.0290) than subjects with CC genotype. A recessive model of rs6982567 was statistically significantly associated with PCV (odds ratio, 2.29; 95% confidence interval, 1.04-5.05; p = 0.0351). However, the association did not withstand stringent Bonferroni correction. There were no significant differences in genotype distributions or models in nAMD.

Conclusions

There was a possible weak association between the rs6982567 near GDF6 and PCV in this replication study with an independent Han Chinese cohort. A complete survey of the GDF6 locus with a larger sample size is needed in future studies.

SUBMITTER: Ji Y

PROVIDER: S-EPMC4251681 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Association of rs6982567 near GDF6 with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Han Chinese cohort.

Ji Yuying Y Zhang Xiongze X Wu Kunfang K Su Yu Y Li Meng M Zuo Chengguo C Wen Feng F

BMC ophthalmology 20141122

<h4>Background</h4>Growth differentiation factor 6 (GDF6) has been reported to be a novel disease gene for age-related macular degeneration (AMD) in Caucasians. This study aimed to investigate whether rs6982567 was associated with neovascular AMD (nAMD) or polypoidal choroidal vasculopathy (PCV) in a Han Chinese cohort.<h4>Methods</h4>A total of 612 participants (251 PCV patients, 157 nAMD patients and 204 controls) were included in this study. The SNaPshot system was used to genotype the rs6982 ...[more]

PMID: 25416513

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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:BackgroundTo compare the choriocapillary flow density (CFD) among the fellow eyes of polypoidal choroidal vasculopathy (PCV), neovascular age-related macular degeneration (nAMD), and healthy controls using spectral-domain optical coherence angiography tomography (SD-OCTA).MethodsThis is a cross-sectional study that includes the fellow eyes of 38 patients with unilateral PCV, 36 patients with unilateral nAMD, and 36 eyes from 36 healthy volunteers. The PCV group was further classified into polypoidal CNV (P-CNV) and typical PCV (T-PCV) for subgroup analysis. The age, subfoveal choroidal thickness (SFCT), Age-Related Eye Disease Study (AREDS) classification, and fellow eye diagnosis were acquired. All subjects underwent SD-OCTA with a 6.0-mm scan pattern. Circles with radius of 1.00, 1.50, and 3.00?mm were manually selected in the choriocapillaris (CC) slab, and the CFD was calculated as the percentage of the flow area to the whole selected area as CFD-1.00, 1.50, and 3.00, respectively. Univariate and multivariate analysis were performed to study the correlation between the aforementioned factors with CFD.ResultsThe mean CFD-1.00, 1.50, and 3.00 of the nAMD group were 61.51, 63.18, and 66.20, respectively; these were significantly lower than those of the PCV group (65.90, 66.89, and 67.94; P?<?0.001, P?<?0.001, and P?=?0.010; respectively) and control group (66.28, 66.96, and 68.42; P?<?0.001, P?<?0.001, and P?=?0.001, respectively), and no difference was detected between the PCV and control group or between PCV subtypes. The AREDS classification and fellow eye diagnosis were correlated with CFD in univariate analysis; however, only the fellow eye diagnosis showed a significant correlation after multiple linear regression.ConclusionsThe CFD of nAMD fellow eyes was significantly lower than that of PCV and control eyes, and no difference was detected between PCV and control group, indicating that CC loss plays a different role in the early pathogenesis of nAMD and PCV.

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

Association of rs6982567 near GDF6 with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Han Chinese cohort.

Background

Methods

Results

Conclusions

Publications

Association of rs6982567 near GDF6 with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Han Chinese cohort.

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