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

PLoS One. 2013 Nov 7;8(11):e79767. doi: 10.1371/journal.pone.0079767. eCollection 2013.


Glycated hemoglobin A1C (HbA1C) 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 HbA1C 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 HbA1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA1C 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 HbA1C 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 HbA1C 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian Continental Ancestry Group / genetics*
  • Diabetic Retinopathy / blood*
  • Diabetic Retinopathy / epidemiology
  • Diabetic Retinopathy / genetics*
  • Ethnic Groups / genetics
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Association Studies*
  • Genome-Wide Association Study
  • Genotype
  • Glycated Hemoglobin A / genetics*
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / epidemiology
  • Renal Insufficiency, Chronic / genetics*
  • Singapore
  • Young Adult


  • Glycated Hemoglobin A

Grant support

This project acknowledges the support of the Yong Loo Lin School of Medicine, the National University Health System and the Life Sciences Institute from the National University of Singapore. The authors also acknowledge the support from the National Research Foundation (NRF-RF-2010-05), National Medical Research Council of Singapore (under the clinician scientist award, Singapore Translational Research Investigator Award and individual research grant schemes) and the Biomedical Research Council of Singapore (under the individual research grants scheme). SiMES, SINDI and SCES were funded by National Medical Research Council (grants 0796/2003, IRG07nov013, IRG09nov014, STaR/0003/2008; CG/SERI/2010) and Biomedical Research Council (grants 08/1/35/19/550, 09/1/35/19/616). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.