HLA class II genotypes are not associated with age related macular degeneration in a case-control, population-based study.
Ontology highlight
ABSTRACT:
SUBMITTER: Pappas D
PROVIDER: S-EPMC4476503 | biostudies-literature | 2015 Mar
REPOSITORIES: biostudies-literature
Publications
HLA class II genotypes are not associated with age related macular degeneration in a case-control, population-based study.
Pappas Derek D Hollenbach Jill J Coleman Anne L AL Gorin Michael B MB Yu Fe F Williams Kevin K Noble Janelle J Tranah Gregory J GJ
Human immunology 20150207 2-3
Multiple lines of evidence support an immunologic basis and genetic disposition for the development of age-related macular degeneration (AMD). Comprehensive human leukocyte antigens (HLA) class II typing at four loci (DRB1, DQA1, DQB1, and DPB1) was assessed using next generation sequencing methods and tested for association with age-related macular degeneration (AMD) in a case-control study of 456 AMD cases and 499 controls from the population-based Study of Osteoporotic Fractures (SOF) cohort. ...[more]
Similar Datasets
Project description:Most available studies focusing on the association between neovascular age-related macular degeneration (AMD) and dementia have conflicting results. This study aimed to investigate the association between previously diagnosed AMD and dementia using a population-based dataset in Taiwan.Data for this case-control study were retrospectively collected from the Taiwan National Health Insurance Research Database. We identified 13,402 subjects who had a diagnosis of dementia as cases, and 40,206 subjects without dementia as controls. A conditional logistic regression was used to examine the association of dementia with previously diagnosed neovascular AMD.We found that of the study sample of 53,608 subjects, 1.01% had previously diagnosed neovascular AMD, 1.35% and 0.90% for cases and the controls, respectively (p<0.001). The conditional logistic regression analysis suggested that the odds ratio of prior neovascular AMD for cases was 1.37 (95% confidence interval: 1.14~1.65) compared to the controls after adjusting for subjects' age, monthly income, geographic location, urbanization level, and hyperlipidemia, diabetes, hypertension, stroke, ischemic heart disease, and whether or not a subjects underwent cataract surgery prior to index date than controls.Dementia subjects were associated with a higher proportion of prior neovascular AMD than were the controls.
| S-EPMC4352026 | biostudies-other
Project description:BACKGROUND: Onset and development of the multifactorial disease age-related macular degeneration (AMD) are highly interrelated with mitochondrial functions such as energy production and free radical turnover. Mitochondrial dysfunction and overproduction of reactive oxygen species may contribute to destruction of the retinal pigment epithelium, retinal atrophy and choroidal neovascularization, leading to AMD. Consequently, polymorphisms of the mitochondrial genome (mtDNA) are postulated to be susceptibility factors for this disease. Previous studies from Australia and the United States detected associations of mitochondrial haplogroups with AMD. The aim of the present study was to test these associations in Middle European Caucasians. METHODOLOGY/PRINCIPAL FINDINGS: Mitochondrial haplogroups (combinations of mtDNA polymorphisms) and mitochondrial CR polymorphisms were analyzed in 200 patients with wet AMD (choroidal neovascularization, CNV), in 66 patients with dry AMD, and in 385 controls from Austria by means of multiplex primer extension analysis and sequencing, respectively. In patients with CNV, haplogroup H was found to be significantly less frequent compared to controls, and haplogroup J showed a trend toward a higher frequency compared to controls. Five CR polymorphisms were found to differ significantly in the two study populations compared to controls, and all, except one (T152C), are linked to those haplogroups. CONCLUSIONS/SIGNIFICANCE: It can be concluded that haplogroup J is a risk factor for AMD, whereas haplogroup H seems to be protective for AMD.
| S-EPMC3278404 | biostudies-literature
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.
| S-EPMC7821082 | biostudies-literature
Project description:BACKGROUND:Lipids are implicated in the pathogenesis of age-related macular degeneration (AMD). The relationship between systemic lipids and AMD has not been well characterized. The objective was to investigate the relationship between serum lipids and AMD in older adults using a lipidomic approach. METHODS:In a case-control study, 240 adults, aged ?66?years, a third each having geographic atrophy, neovascular AMD, or no signs of AMD, were selected from a population-based sample of participants in the Age Gene/Environment Susceptibility-Reykjavik Study. The exposure was serum lipids and risk factors for AMD. The outcome was late AMD, assessed through fundus images taken through dilated pupils using a 45-degree digital camera and grading for neovascular AMD and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. RESULTS:Of 177 serum lipid species measured, there were no significant differences in serum lipids between controls and those with geographic atrophy or neovascular AMD, respectively. Adults with neovascular AMD had higher total serum lysophosphatidylcholine (LPC) (P?=?0.004) and serum LPC 18:0 (P?=?0.0002) compared to those with geographic atrophy. CONCLUSION:Late AMD was not characterized by alterations in systemic lipids compared with normal controls. These findings suggest that there may be differences in the LPC pathway between adults with neovascular AMD and geographic atrophy.
| S-EPMC6323843 | biostudies-literature
Project description:BACKGROUND/AIMS:Phenotypic discordance in monozygotic (MZ) twin pairs can have an epigenetic or genetic basis. Although age-related macular degeneration (AMD) has a strong genetic component, few studies have addressed its epigenetic basis. METHODS:Using SNP arrays, we evaluated differences in copy number variation (CNV) and allele-specific methylation (ASM) patterns (via methyl-sensitive restriction enzyme digestion of DNA) in MZ twin pairs from the US Twin Study of AMD. Further analyses examined the relationship between ASM and CNVs with AMD by both case/control analysis of ASM at candidate regions and by analysis of ASM and CNVs in twins discordant for AMD. RESULTS:The frequency of ASM sites differs between cases and controls in regions surrounding the AMD candidate genes CFH, C2 and CFB. While ASM patterns show a substantial dependence on local sequence polymorphisms, we observed dissimilar patterns of ASM between MZ twins. The genes closest to the sites where discordant MZ twins have dissimilar patterns of ASM are enriched for genes implicated in gliosis, a process associated with neovascular AMD. Similar twin-based analyses revealed no AMD-associated CNVs. CONCLUSIONS:Our results provide evidence of epigenetic influences beyond the known genetic susceptibility and implicate inflammatory responses and gliosis in the etiology of AMD.
| S-EPMC6476332 | biostudies-literature
Project description:PurposeAge-related macular degeneration (AMD) is a multifactorial blinding disease in the elderly. LOC387715 harbors a single-nucleotide polymorphism that has an association with AMD. This study was conducted to confirm the association between LOC387715 and AMD and to refine estimates of the impact of this gene variation in using samples from three studies: an Australian population-based study and two U.S. clinic-based case-control studies.MethodsCases and controls were collected from a National Eye Institute (NEI) clinical protocol (n = 240), the Age-Related Eye Disease Study (AREDS; n = 488), and the Blue Mountains Eye Study (BMES; n = 851). After DNA extraction, subjects were genotyped for the LOC387715 Ala69Ser polymorphism (rs10490924).ResultsThe combined NEI and AREDS samples yielded odds ratios (ORs) of 2.61 (95% CI 1.89-3.61, P = 1.42 x 10(-9)) and 8.59 (95% CI 4.49-16.5, P = 3.56 x 10(-13)) for the heterozygous and homozygous risk alleles, respectively. The corresponding odds ratios in the BMES sample were 1.69 (95% CI: 1.25-2.28, P = 0.0007) and 2.20 (95% CI: 1.05-4.62, P = 0.038) for the heterozygous and homozygous groups. Neither set of samples showed statistically significant interaction with smoking, although there appeared to be a trend of interaction between smoking and LOC387715 for risk of advanced AMD.ConclusionsAlthough these data from three case-control samples support an AMD genetic risk marker harbored within LOC387715, the nested case-control data from the population-based BMES samples showed lower estimates than from the clinic-based samples. This may be because the BMES samples consisted of largely early AMD cases while the clinic-based AMD samples consisted exclusively of advanced cases.
| S-EPMC1885234 | biostudies-literature
Project description:Age-related macular degeneration is an eye disease that is the main cause of legal blindness in the elderly in developed countries. Despite this, its pathogenesis is not completely known, and many genetic, epigenetic, environmental and lifestyle factors may be involved. Vision loss in age-related macular degeneration (AMD) is usually consequence of the occurrence of its wet (neovascular) form that is targeted in the clinic by anti-VEGF (vascular endothelial growth factor) treatment. The wet form of AMD is associated with the accumulation of cellular waste in the retinal pigment epithelium, which is removed by autophagy and the proteosomal degradation system. In the present work, we searched for the association between genotypes and alleles of single nucleotide polymorphisms (SNPs) of autophagy-related genes and wet AMD occurrence in a cohort of Finnish patients undergoing anti-VEGF therapy and controls. Additionally, the correlation between treatment efficacy and genotypes was investigated. Overall, 225 wet AMD patients and 161 controls were enrolled in this study. Ten SNPs (rs2295080, rs11121704, rs1057079, rs1064261, rs573775, rs11246867, rs3088051, rs10902469, rs73105013, rs10277) in the mTOR (Mechanistic Target of Rapamycin), ATG5 (Autophagy Related 5), ULK1 (Unc-51-Like Autophagy Activating Kinase 1), MAP1LC3A (Microtubule Associated Protein 1 Light Chain 3 α), SQSTM1 (Sequestosome 1) were analyzed with RT-PCR-based genotyping. The genotype/alleles rs2295080-G, rs11121704-C, rs1057079-C and rs73105013-T associated with an increased, whereas rs2295080-TT, rs2295080-T, rs11121704-TT, rs1057079-TT, rs1057079-T, rs573775-AA and rs73105013-C with a decreased occurrence of wet AMD. In addition, the rs2295080-GG, rs2295080-GT, rs1057079-TT, rs11246867-AG, rs3088051-CC and rs10277-CC genotypes were a positively correlated cumulative number of anti-VEGF injections in 2 years. Therefore, variability in autophagy genes may have an impact on the risk of wet AMD occurrence and the efficacy of anti-VEGF treatment.
| S-EPMC7694766 | biostudies-literature
Project description:IntroductionPrevious studies evaluating the association between clinically diagnosed Alzheimer's disease (AD) and age-related macular degeneration (AMD) have generated conflicting results. This study is the first to assess whether AMD prevalence is higher in AD patients than non-AD controls by using histopathology to definitively diagnose AD.MethodsThis was a retrospective case-control study utilizing diagnostic information extracted from autopsy reports of patients age 75 and above, including 115 with a neuropathological diagnosis of AD and 57 age-matched normal controls.ResultsThe rate of AMD was not significantly higher in AD cases (53.0%) than in controls (59.6%) (z = 0.820, p = 0.794). AMD severity as determined by Sarks score was similar between AD patients and controls (χ2 = 2.96, p = 0.706). There was also no significant association between Braak stage of AD severity and AMD (χ2 = 4.55, p = 0.602).DiscussionNo significant effect of AD diagnosis or pathologic severity on AMD comorbidity was found, suggesting that any shared mechanisms between AMD and AD may be nondeterministic.
| S-EPMC6768473 | biostudies-literature
Project description:PurposeInnate 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.MethodsAMD 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.ResultsNeither 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.ConclusionsEven 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.
| S-EPMC2894575 | biostudies-literature
Project description:ObjectiveTo assess the association and combined effect on the risk of age-related macular degeneration (AMD) by the HtrA1 and complement factor H (CFH) polymorphisms, smoking, and serum cholesterol.DesignClinic-based and population-based case control study.ParticipantsA total of 805 AMD cases and 921 controls from The Eye Clinic of National Eye Institute, Age-Related Eye Diseases Study, Blue Mountain Eye Study Cohort, and Minnesota Lions Eye Bank.MethodsDNA samples were genotyped for polymorphisms of rs11200638 in HtrA1 promoter and rs380390 in CFH. HtrA1 protein in ocular tissue was measured. Interactions of the HtrA1 risk allele with the CFH risk variant, smoking status, and cholesterol were assessed.Main outcome measuresAMD was evaluated by retinal specialists, and AMD subtypes (geographic atrophy and neovascularization) were determined.ResultsStrong associations of the HtrA1 risk allele (A) with AMD were present in all sample sets. A similar magnitude of association was observed for central geographic atrophy and neovascular AMD. The combination of the HtrA1 and CFH risk alleles increased AMD susceptibility, as did the combination of the HtrA1 risk allele with smoking. No combined effect of HtrA1 risk allele and cholesterol level was found. Enhanced expression of HtrA1 protein was detected in retina with AMD.ConclusionsFindings from multiple samples support an AMD genetic variant harbored within HtrA1. The risk of advanced AMD increased when the presence of risk alleles from HtrA1 was combined with either CFH risk alleles or history of smoking.
| S-EPMC2610681 | biostudies-literature