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SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

Kondo N, Bessho H, Honda S, Negi A - Mol. Vis. (2009)

Bottom Line: 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.A meta-analysis of the association between the V16A variant and neovascular AMD also failed to detect a significant association.We found no evidence to support the role of any common SOD2 variations including the V16A variant in the susceptibility to neovascular AMD or PCV.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan. nskondo@gmail.com

ABSTRACT

Purpose: A 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.

Methods: In 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.

Results: We 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.

Conclusions: We 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.

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Related in: MedlinePlus

Meta-analysis of the V16A variant for its association with neovascular AMD. Odds ratios (ORs, black squares) and 95% confidence intervals (CIs, bars) are presented for each study. Also shown is the shaded diamond of the summary OR using the random-effects model of DerSimonian and Laird [52]. The genotype data included in the meta-analysis refer to the description of Kimura et al. [33] and Gotoh et al. [35]. Heterogeneity between studies was tested using Cochran’s Q statistic [53,54] and the I2 statistic for inconsistency [53,54]. Abbreviations: AMD represents age-related macular degeneration.
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f1: Meta-analysis of the V16A variant for its association with neovascular AMD. Odds ratios (ORs, black squares) and 95% confidence intervals (CIs, bars) are presented for each study. Also shown is the shaded diamond of the summary OR using the random-effects model of DerSimonian and Laird [52]. The genotype data included in the meta-analysis refer to the description of Kimura et al. [33] and Gotoh et al. [35]. Heterogeneity between studies was tested using Cochran’s Q statistic [53,54] and the I2 statistic for inconsistency [53,54]. Abbreviations: AMD represents age-related macular degeneration.

Mentions: Finally, a meta-analysis was performed to assess the association of the V16A variant with neovascular AMD across the different independent studies. Association results from our study (only neovascular AMD) and the two previous Japanese studies [33,35] were combined using the random-effects model of DerSimonian and Laird [52], and a summary OR for the model was calculated based on the allele frequency data. As shown in Figure 1, the heterogeneity test across studies (Cochran’s Q statistic) was significant for this variant (p=0.0014), and inconsistency of the genetic effects across the three studies was high (I2=84.8%). No significant association was detected for the V16A variant, with a random-effects summary OR of 0.89 (95% CI, 0.47–1.67). Allele and genotype frequencies of the V16A variant observed in the two previous Japanese studies [33,35] are shown in Table 4.


SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

Kondo N, Bessho H, Honda S, Negi A - Mol. Vis. (2009)

Meta-analysis of the V16A variant for its association with neovascular AMD. Odds ratios (ORs, black squares) and 95% confidence intervals (CIs, bars) are presented for each study. Also shown is the shaded diamond of the summary OR using the random-effects model of DerSimonian and Laird [52]. The genotype data included in the meta-analysis refer to the description of Kimura et al. [33] and Gotoh et al. [35]. Heterogeneity between studies was tested using Cochran’s Q statistic [53,54] and the I2 statistic for inconsistency [53,54]. Abbreviations: AMD represents age-related macular degeneration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2742636&req=5

f1: Meta-analysis of the V16A variant for its association with neovascular AMD. Odds ratios (ORs, black squares) and 95% confidence intervals (CIs, bars) are presented for each study. Also shown is the shaded diamond of the summary OR using the random-effects model of DerSimonian and Laird [52]. The genotype data included in the meta-analysis refer to the description of Kimura et al. [33] and Gotoh et al. [35]. Heterogeneity between studies was tested using Cochran’s Q statistic [53,54] and the I2 statistic for inconsistency [53,54]. Abbreviations: AMD represents age-related macular degeneration.
Mentions: Finally, a meta-analysis was performed to assess the association of the V16A variant with neovascular AMD across the different independent studies. Association results from our study (only neovascular AMD) and the two previous Japanese studies [33,35] were combined using the random-effects model of DerSimonian and Laird [52], and a summary OR for the model was calculated based on the allele frequency data. As shown in Figure 1, the heterogeneity test across studies (Cochran’s Q statistic) was significant for this variant (p=0.0014), and inconsistency of the genetic effects across the three studies was high (I2=84.8%). No significant association was detected for the V16A variant, with a random-effects summary OR of 0.89 (95% CI, 0.47–1.67). Allele and genotype frequencies of the V16A variant observed in the two previous Japanese studies [33,35] are shown in Table 4.

Bottom Line: 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.A meta-analysis of the association between the V16A variant and neovascular AMD also failed to detect a significant association.We found no evidence to support the role of any common SOD2 variations including the V16A variant in the susceptibility to neovascular AMD or PCV.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan. nskondo@gmail.com

ABSTRACT

Purpose: A 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.

Methods: In 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.

Results: We 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.

Conclusions: We 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.

Show MeSH
Related in: MedlinePlus