Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III)

BMC Medical Genetics

Research Article

Josée Dupuis¹  Bianca C Porneala²  Jason L Vassy³  Jonna L Grimsby³  James B Meigs³  José C Florez⁴  Ajay Yesupriya⁵  Muin J Khoury⁵  Nicole F Dowling⁵  Renee M Ned⁵  Tiebin Liu⁵  Man-Huei Chang⁵  Quanhe Yang⁵ 

[1] Boston University School of Public Health, Boston, MA, USA;National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA;General Medicine Division, Massachusetts General Hospital, Boston, MA, USA;General Medicine Division, Massachusetts General Hospital, Boston, MA, USA;Harvard Medical School, Boston, MA, USA;General Medicine Division, Massachusetts General Hospital, Boston, MA, USA;Harvard Medical School, Boston, MA, USA;Diabetes Unit and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA;Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA;Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, GA, USA;

关键词: HbA1c Level;    Genetic Risk Score;    Mexican American;    Genotype Score;    Risk Allele Frequency;   

DOI  :  10.1186/1471-2350-13-30

 received in 2011-10-12, accepted in 2012-04-27,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundHemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality.MethodsWe studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey) III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American) to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05.ResultsRAFs varied widely and at six loci race-ethnic differences in RAF were significant (p < 0.0002), with NHB usually the most divergent. For instance, at ATP11A, the SNP RAF was 54% in NHB, 18% in MA and 14% in NHW (p < .0001). The mean genotype score differed by race-ethnicity (NHW: 10.4, NHB: 11.0, MA: 10.7, p < .0001), and was associated with increase in HbA1c in NHW (β = 0.012 HbA1c increase per risk allele, p = 0.04) and MA (β = 0.021, p = 0.005) but not NHB (β = 0.007, p = 0.39). The genotype score was not associated with mortality in any group (NHW: OR (per risk allele increase in mortality) = 1.07, p = 0.09; NHB: OR = 1.04, p = 0.39; MA: OR = 1.03, p = 0.71).ConclusionAt many HbA1c loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA1c-associated variants on HbA1c levels varied by race-ethnicity, but did not influence mortality.

【 授权许可】

Unknown   
© Grimsby et al.; licensee BioMed Central Ltd. 2012. 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.