Dataset Information

Association of toll-like receptor 3 polymorphism rs3775291 with age-related macular degeneration: a systematic review and meta-analysis.

ABSTRACT: Association of a polymorphism rs3775291 in the toll-like receptor 3 (TLR3) gene with age-related macular degeneration (AMD) had been investigated intensively, with variable results across studies. Here we conducted a meta-analysis to verify the effect of rs3775291 on AMD. We searched for genetic association studies published in PubMed, EMBASE and Web of Science from start dates to March 10, 2015. Totally 235 reports were retrieved and 9 studies were included for meta-analysis, involving 7400 cases and 13579 controls. Summary odds ratios (ORs) with 95% confidence intervals (CIs) for alleles and genotypes were estimated. TLR3 rs3775291 was associated with both geographic atrophy (GA) and neovascular AMD (nAMD), with marginally significant pooled-P values. Stratification analysis by ethnicity indicated that rs3775291 was associated with all forms of AMD, GA and nAMD only in Caucasians (OR = 0.87, 0.78 and 0.77, respectively, for the TT genotype) but not in East Asians. However, the associations could not withstand Bonferroni correction. This meta-analysis has thus revealed suggestive evidence for TLR3 rs3775291 as an associated marker for AMD in Caucasians but not in Asians. This SNP may have only a small effect on AMD susceptibility. Further studies in larger samples are warranted to confirm its role.

SUBMITTER: Ma L

PROVIDER: S-EPMC4726375 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Association of toll-like receptor 3 polymorphism rs3775291 with age-related macular degeneration: a systematic review and meta-analysis.

Ma Li L Tang Fang Yao FY Chu Wai Kit WK Young Alvin L AL Brelen Marten E ME Pang Chi Pui CP Chen Li Jia LJ

Scientific reports 20160122

Association of a polymorphism rs3775291 in the toll-like receptor 3 (TLR3) gene with age-related macular degeneration (AMD) had been investigated intensively, with variable results across studies. Here we conducted a meta-analysis to verify the effect of rs3775291 on AMD. We searched for genetic association studies published in PubMed, EMBASE and Web of Science from start dates to March 10, 2015. Totally 235 reports were retrieved and 9 studies were included for meta-analysis, involving 7400 cas ...[more]

PMID: 26796995

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Project description:PurposeWe previously identified a genetic copy number polymorphism (CNP147) that was statistically associated with age-related macular degeneration (AMD) and that resides downstream of the complement factor H (CFH) gene. Factor H protein is polymorphic at amino acid 402, in which the resulting histidine containing moiety has been established to impart significant risk of AMD. We present a method to precisely determine the exact copy number of CNP147 and examine in more detail the association with AMD.DesignCase-control study.ParticipantsA total of 421 Age-Related Eye Disease Study (AREDS) subjects, of whom approximately 35% were diagnosed with neovascular disease, 19% were diagnosed with geographic atrophy, 16% were diagnosed with both, 30% were diagnosed with large drusen, and 215 were controls.MethodsBy using copy number assays available from Applied Biosystems Inc. (Carlsbad, CA), we examined 4 loci spanning CNP147 and neighboring CNP148 in an AREDS matched case-control sample set. We analyzed these data by copy number while controlling for 2 high-risk CFH variants, rs1061170 (Y402H) and rs1410996. We phased the high-risk CFH variants with CNP147 and analyzed haplotype frequencies in cases and controls. To further validate copy numbers, 6 Utah Centre D'etude du Polymorphism Humaine (CEPH) families were typed for CNP147, and the segregation was assessed.Main outcome measuresIncreased or decreased risk of AMD from genetic loci.ResultsHaving fewer than 2 copies of CNP147 was associated with an estimated 43% reduction in odds of having AMD in this sample set (adjusted odds ratio [OR] = 0.57, P=0.006). CNP148 variation is rare in Caucasians and was not statistically significant. Common haplotypes reveal that the risk alleles for rs1061170 and rs1410996 most frequently segregate with higher copy numbers for CNP147, but not exclusively, and that 1 haplotype that carried a deletion of CNP147 was highly protective (OR = 0.25 P=1.3×10(-13)) when compared with the reference.ConclusionsIn this matched subset of AREDS subjects, after adjusting for 2 known risk variants in CFH, CNP147 deletion statistically associates with diminished risk for AMD.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Dataset Information

Association of toll-like receptor 3 polymorphism rs3775291 with age-related macular degeneration: a systematic review and meta-analysis.

Publications

Association of toll-like receptor 3 polymorphism rs3775291 with age-related macular degeneration: a systematic review and meta-analysis.

Similar Datasets

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