Association of hypoxia inducible factor-1 alpha gene polymorphism with both type 1 and type 2 diabetes in a Caucasian Hungarian sampleReportar como inadecuado

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BMC Medical Genetics

, 10:79

First Online: 19 August 2009Received: 05 March 2009Accepted: 19 August 2009


BackgroundHypoxia inducible factor-1 alpha HIF-1α is a transcription factor that plays an important role in neo-vascularisation, embryonic pancreas beta-cell mass development, and beta cell protection. Recently a non synonymous single nucleotide polymorphism g.C45035T SNP, rs11549465 of HIF-1α gene, resulting in the p.P582S amino acid change has been shown to be associated with type 2 diabetes T2DM in a Japanese population. Our aim was to replicate these findings on a Caucasian Hungarian population, as well as to study whether this genetic effect is restricted to T2DM or can be expanded to diabetes in general.

MethodsA large Caucasian sample N = 890 was recruited including 370 T2DM, 166 T1DM and 354 healthy subjects. Genotyping was validated by two independent methods: a restriction fragment analysis RFLP and a real time PCR using TaqMan probes. An overestimation of heterozygotes by RFLP was observed as a consequence of a nearby SNP rs34005929. Therefore genotyping results of the justified TaqMan system were accepted. The measured genotype distribution corresponded to Hardy-Weinberg equilibrium P = 0.740

ResultsAs the TT genotype was extremely rare in the population 0.6% in clinical sample and 2.5% in controls, the genotypes were grouped as T absent CC and T present CT and TT. Genotype-wise analysis showed a significant increase of T present group in controls 24.0% as compared to patients 16.8%, P = 0.008. This genetic effect was demonstrated in the separated samples of type 1 15.1%, P = 0.020, and also in type 2 17.6%, P = 0.032 diabetes. Allele-wise analysis gave identical results showing a higher frequency of the T allele in the control sample 13.3% than in the clinical sample 8.7%, P = 0.002 with similar results in type 1 7.8%, P = 0.010 and type 2 9.1%, P = 0.011 diabetes. The odds ratio for diabetes either type 1 or 2 was 1.56 in the presence of the C allele.

ConclusionWe confirmed the protective effect of a rare genetic variant of HIF-1α gene against type 2 diabetes in a Caucasian sample. Moreover we demonstrated a genetic contribution of the same polymorphism in type 1 diabetes as well, supporting a possible overlap in pathomechanism for T2DM and a T1DM.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-10-79 contains supplementary material, which is available to authorized users.

Geza Nagy, Reka Kovacs-Nagy contributed equally to this work.

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Autor: Geza Nagy - Reka Kovacs-Nagy - Eva Kereszturi - Aniko Somogyi - Anna Szekely - Nora Nemeth - Nora Hosszufalusi - Pal Pancz



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