RESUMO
Purpose: Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion that predisposes the patient to retinal detachment. It has been suggested that collagen type II alpha 1 (COL2A1) gene variants may contribute to the development of disorders associated with retinal detachment. Here we investigated whether COL2A1 gene variants were associated with the risk of lattice degeneration of the retina. Methods: We recruited 634 Japanese patients with lattice degeneration of the retina and 1694 Japanese healthy controls. We genotyped 13 tagging single-nucleotide polymorphisms (SNPs) in COL2A1. We also performed imputation analysis to evaluate the potential association of un-genotyped COL2A1 SNPs, involving the imputation of 65 SNPs. Results: Two intronic SNPs-rs1793954 and rs1635533-were significantly associated with lattice degeneration of the retina. The SNP rs1793954 showed the strongest association, with its C allele carrying an increased disease risk (p = 0.0016, corrected p = 0.021, OR = 1.25). The rs1793954 and rs1635533 SNPs were in strong linkage disequilibrium with each other (r 2 = 0.99), and conditional analysis revealed that rs1793954 could account for the association between rs1635533 and the disease. Conclusions: Our results suggested that COL2A1 gene variants may contribute to the development of lattice degeneration of the retina. Further genetic and functional analyses of COL2A1 variants are needed to clarify the present findings.
Assuntos
Povo Asiático/genética , Colágeno Tipo II/genética , Predisposição Genética para Doença , Mutação/genética , Degeneração Retiniana/genética , Alelos , Humanos , Japão , Desequilíbrio de Ligação/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS) using a dense panel of 23,465 microsatellite markers covering the entire human genome. This GWAS in a Japanese cohort (294 patients with lattice degeneration and 294 controls) led to the identification of one microsatellite locus, D2S0276i, in the collagen type IV alpha 4 (COL4A4) gene on chromosome 2q36.3. To validate the significance of this observation, we evaluated the D2S0276i region in the GWAS cohort and in an independent Japanese cohort (280 patients and 314 controls) using D2S0276i and 47 single nucleotide polymorphisms covering the region. The strong associations were observed in D2S0276i and rs7558081 in the COL4A4 gene (Pc = 5.8 × 10(-6), OR = 0.63 and Pc = 1.0 × 10(-5), OR = 0.69 in a total of 574 patients and 608 controls, respectively). Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina.
Assuntos
Colágeno Tipo IV/genética , Predisposição Genética para Doença , Variação Genética , Degeneração Retiniana/genética , Descolamento Retiniano/genética , Alelos , Estudos de Casos e Controles , Regulação da Expressão Gênica , Frequência do Gene , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Desequilíbrio de Ligação , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , Serina Endopeptidases/genéticaRESUMO
MYP2 was reported for a candidate locus associated with high grade myopia by linkage analysis, but no candidate gene has been detected. We report an association study in the Japanese population using 750 microsatellite markers on chromosome 18 that include MYP2 locus. 450 Japanese subjects with high myopia whose refractive error was greater than or equal to -9.25D in at least one eye and equal number of normal control subjects were recruited in this study. Three steps screening on the pooled DNA of patients and the pooled DNA of controls were performed in this study. A total of 722 microsatellite markers could be analyzed, and we obtained 4 positive markers. Then to avoid experimental errors and artifacts, we confirmed true allele frequency by individual genotyping using initial set of 450 patients and controls. Only marker D18S0301i showed statistically significance, and no marker showed statistically significance on the MYP2 locus. Near the marker D18S0301i, GALNT1 gene was located, but its relation to high myopia has remained to be identified.