Abstract

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.

Highlights

  • Glycated hemoglobin A1C (HbA1C) is formed through the nonenzymatic glycation of hemoglobin

  • In patients with diabetes mellitus, it is used as a therapeutic target against which glucose lowering therapies can be titrated, as it shows a good correlation with the risk of developing microvascular complications associated with diabetes mellitus

  • Several genome-wide association studies (GWAS) have been conducted in populations of European ancestry: a GWAS conducted in 14,618 women identified 4 loci harboring variants associated with HbA1C [4]; a study of 1,782 Europeans found suggestive evidence for an association with HbA1C at the TCF7L2 locus [5]; and a meta-analysis of 31 genome-wide studies across 68,000 European samples revealed 10 loci harboring variants associated with HbA1C [6]

Read more

Summary

Introduction

Glycated hemoglobin A1C (HbA1C) is formed through the nonenzymatic glycation of hemoglobin. In patients with diabetes mellitus, it is used as a therapeutic target against which glucose lowering therapies can be titrated, as it shows a good correlation with the risk of developing microvascular complications associated with diabetes mellitus. It shows less intra-individual variability than both fasting glucose and 2 hour post challenge glucose after an oral glucose tolerance test and can be measured without the need for fasting. HbA1C levels show significant heritability, with twin studies conducted in Europeans estimating a heritability of 75% [3].

Objectives
Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call