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Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples.

ABSTRACT: PURPOSE:Innate immunity appears to play a key role in age-related macular degeneration (AMD). Although two previous studies reported that gene variations in Toll-like receptor (TLR)-3 and -4 are associated with AMD, other studies have not confirmed these associations. In this study, three independent samples (two U.S. clinic-based case-control study samples and one Australian population-based study sample) were used to further assess the association of the polymorphisms rs3775291 in TLR3 and rs4986790 in TLR4 with AMD. METHODS:AMD cases and unrelated controls were collected from the National Eye Institute Clinical Center (NEI, n = 320), the Age-Related Eye Disease Study (AREDS, n = 483), and the Blue Mountains Eye Study (BMES, n = 852). DNA extracted from subjects was genotyped for rs3775291 and rs4986790, and the associations with AMD were investigated. RESULTS:Neither of the two polymorphisms rs3775291 and rs4986790 had a statistically significant association with AMD in any of the three sample sets or in combinations of the sets. Analysis of the combined geographic atrophy or neovascular AMD cases in the NEI, AREDS, and BMES sample sets also failed to demonstrate statistically significant associations of those two single nucleotide polymorphisms with advanced AMD. CONCLUSIONS:Even with previously verified samples sets and adequate study powers, the results did not confirm the reported associations of TLR3 rs3775291 and TLR4 rs4986790 with AMD in the three independent samples, individually or combined.

SUBMITTER: Cho Y

PROVIDER: S-EPMC2894575 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples.

Cho Youngeun Y Wang Jie Jin JJ Chew Emily Y EY Ferris Frederick L FL Mitchell Paul P Chan Chi-Chao CC Tuo Jingsheng J

Investigative ophthalmology & visual science 20090723 12

<h4>Purpose</h4>Innate immunity appears to play a key role in age-related macular degeneration (AMD). Although two previous studies reported that gene variations in Toll-like receptor (TLR)-3 and -4 are associated with AMD, other studies have not confirmed these associations. In this study, three independent samples (two U.S. clinic-based case-control study samples and one Australian population-based study sample) were used to further assess the association of the polymorphisms rs3775291 in TLR3 ...[more]

PMID: 19628747

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Project description:ImportanceAge-related macular degeneration (AMD), the leading cause of irreversible blindness in older adults, appears to have no effective preventive measures. The common antidiabetic drug metformin has been shown to have protective outcomes in multiple age-associated diseases and may have the potential to protect against the development of AMD.ObjectiveTo determine whether metformin use is associated with reduced odds of developing AMD.Design, setting, and participantsThis case-control study of patients from a nationwide health insurance claims database included a population-based sample of patients. Those aged 55 years and older with newly diagnosed AMD from January 2008 to December 2017 were defined as cases and matched with control participants. Data analyses were completed from June 2019 to February 2020.ExposuresDosage of metformin and exposure to other prescribed medications, as identified from outpatient drug claims.Main outcomes and measuresRisk of developing AMD.ResultsA total of 312 404 affected individuals were included (181 817 women [58.2%]). After matching, 312 376 control participants were included (172 459 women [55.2%]; age range, 55 to 107 years). The case group had a slightly higher percentage of participants with diabetes (81 262 participants [26.0%]) compared with the control group (79 497 participants [25.5%]). Metformin use was associated with reduced odds of developing AMD (odds ratio [OR], 0.94 [95% CI, 0.92-0.96]). This association was dose dependent, with low to moderate doses of metformin showing the greatest potential benefit (dosages over 2 years: 1-270 g, OR, 0.91 [95% CI, 0.88-0.94]; 271-600 g, OR, 0.90 [95% CI, 0.87-0.93]; 601-1080 g, OR, 0.95 [95% CI, 0.92-0.98]). Doses of more than 1080 g of metformin over 2 years did not have reduced odds of developing AMD. Both the reduction in odds ratio and the dose-dependent response were preserved in a cohort consisting only of patients with diabetes. Metformin use was associated with a decreased OR of AMD in patients with diabetes without coexisting diabetic retinopathy (OR, 0.93 [95% CI, 0.91-0.95]) but was a risk factor in patients with diabetic retinopathy (OR, 1.07 [95% CI, 1.01-1.15]).Conclusion and relevanceIn this study, metformin use was associated with reduced odds of developing AMD. This association was dose dependent, with the greatest benefit at low to moderate doses. When looking only at patients with diabetes, we saw a preservation of the dose-dependent decrease in the odds of patients developing AMD. Metformin does not appear to be protective in patients with diabetes and coexisting diabetic retinopathy. This study suggests that metformin may be useful as a preventive therapy for AMD and provides the basis for potential prospective clinical trials.

Dataset Information

Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples.

Publications

Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples.

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