Association of genes on chromosome 6, GRIK2 , TMEM217 and TMEM63B (linked to MRPL14 ) with diabetic retinopathy.

PURPOSE: Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM). The susceptibility genes responsible for increasing the risk for DR in type 2 diabetes (T2D) were sought in this study.

METHODS: A case-control study was carried out, comprising 749 unrelated T2D individuals with (n = 174) and without (n = 575) DR. Genotypic distributions of single nucleotide polymorphisms (SNPs) were determined for subjects with and without DR.

RESULTS: Eight chromosome 6 SNPs, having the most significant differences, were delineated: rs10499298, rs10499299, rs17827966, rs1224329, rs1150790, rs713050, rs2518344 and rs487083; all were associated with genes TMEM217, MRPL14 and GRIK2. After adjusting for the duration of DM and levels of hemoglobin A(1c), the TT genotype of rs713050, and the AG + AA genotypes of rs2518344 and rs10499298, differed significantly between those with and without DR. Haplotype analysis revealed haplotype C-A-C, residing in rs10499299, rs10499298 and rs17827966, to have significant linkage disequilibrium.

CONCLUSIONS: We identified new loci on chromosome 6 associated to DR; all loci showed high levels of linkage disequilibrium.