Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes

Abstract

Urinary albumin excretion is an early sign of diabetic kidney disease, affecting every third individual with diabetes. Despite substantial estimated heritability, only variants in the GLRA3 gene have been genome-wide significantly associated (p-value <5 x 10(-8)) with diabetic albuminuria, in Finnish individuals with type 1 diabetes; However, replication attempt in non-Finnish Europeans with type 1 diabetes showed nominally significant association in the opposite direction, suggesting a population-specific effect, but simultaneously leaving the finding controversial. In this study, the association between the common rs10011025 variant in the GLRA3 locus, and albuminuria, was confirmed in 1259 independent Finnish individuals with type 1 diabetes (p = 0.0013), and meta-analysis of all Finnish individuals yielded a genome-wide significant association. The association was particularly pronounced in subjects not reaching the treatment target for blood glucose levels (HbA(1c) > 7%; N = 2560, p = 1.7 x 10(-9)). Even though further studies are needed to pinpoint the causal variants, dissecting the association at the GLRA3 locus may uncover novel molecular mechanisms for diabetic albuminuria irrespective of population background.