In:
BMC Medical Genetics, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2012-12)
Abstract:
Hemoglobin A 1c (HbA 1c ) 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) HbA 1c -associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6 , G 6PC2, GCK, MTNR1B ; 2) association of SNPs with HbA 1c and 3) association of SNPs with mortality. Methods We 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. Results RAFs 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 HbA 1c in NHW (β = 0.012 HbA 1c 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). Conclusion At many HbA 1c loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA 1c -associated variants on HbA 1c levels varied by race-ethnicity, but did not influence mortality.
Type of Medium:
Online Resource
ISSN:
1471-2350
DOI:
10.1186/1471-2350-13-30
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2012
detail.hit.zdb_id:
2041359-2
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