Evaluation of four novel genetic variants affecting hemoglobin A1c levels in a population-based type 2 diabetes cohort (the HUNT2 study)

BMC Medical Genetics

Research Article

Jens K Hertel¹  Stefan Johansson¹  Pål R Njølstad²  Helge Ræder²  Kristian Midthjell³  Kristian Hveem³  Carl GP Platou⁴  Anders Molven⁵ 

[1] Department of Clinical Medicine, University of Bergen, Bergen, Norway;Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway;Department of Clinical Medicine, University of Bergen, Bergen, Norway;Department of Pediatrics, Haukeland University Hospital, Bergen, Norway;HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway;HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway;Department of Internal Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway;The Gade Institute, University of Bergen, Bergen, Norway;Department of Pathology, Haukeland University Hospital, Bergen, Norway;

关键词: Glycemic Control;    HbA1c Level;    Risk Allele;    Genetic Risk Score;    Diabetic Participant;   

DOI  :  10.1186/1471-2350-12-20

 received in 2010-10-12, accepted in 2011-02-04,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundChronic hyperglycemia confers increased risk for long-term diabetes-associated complications and repeated hemoglobin A1c (HbA1c) measures are a widely used marker for glycemic control in diabetes treatment and follow-up. A recent genome-wide association study revealed four genetic loci, which were associated with HbA1c levels in adults with type 1 diabetes. We aimed to evaluate the effect of these loci on glycemic control in type 2 diabetes.MethodsWe genotyped 1,486 subjects with type 2 diabetes from a Norwegian population-based cohort (HUNT2) for single-nucleotide polymorphisms (SNPs) located near the BNC2, SORCS1, GSC and WDR72 loci. Through regression models, we examined their effects on HbA1c and non-fasting glucose levels individually and in a combined genetic score model.ResultsNo significant associations with HbA1c or glucose levels were found for the SORCS1, BNC2, GSC or WDR72 variants (all P-values > 0.05). Although the observed effects were non-significant and of much smaller magnitude than previously reported in type 1 diabetes, the SORCS1 risk variant showed a direction consistent with increased HbA1c and glucose levels, with an observed effect of 0.11% (P = 0.13) and 0.13 mmol/l (P = 0.43) increase per risk allele for HbA1c and glucose, respectively. In contrast, the WDR72 risk variant showed a borderline association with reduced HbA1c levels (β = -0.21, P = 0.06), and direction consistent with decreased glucose levels (β = -0.29, P = 0.29). The allele count model gave no evidence for a relationship between increasing number of risk alleles and increasing HbA1c levels (β = 0.04, P = 0.38).ConclusionsThe four recently reported SNPs affecting glycemic control in type 1 diabetes had no apparent effect on HbA1c in type 2 diabetes individually or by using a combined genetic score model. However, for the SORCS1 SNP, our findings do not rule out a possible relationship with HbA1c levels. Hence, further studies in other populations are needed to elucidate whether these novel sequence variants, especially rs1358030 near the SORCS1 locus, affect glycemic control in type 2 diabetes.

【 授权许可】

Unknown   
© Hertel et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.