A Study Assessing the Association of Glycated Hemoglobin A1C (HbA1C) Associated Variants with HbA1C, Chronic Kidney Disease and Diabetic Retinopathy in Populations of Asian Ancestry

Glycated hemoglobin A(1C) (HbA(1C)) level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA(1C) level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA(1C) levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA(1C) associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA(1C) which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA(1C) with effect sizes similar to those reported in the populations of European ancestry and P-value <= 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study.