Open Access Highly Accessed Research article

Association of hypoxia inducible factor-1 alpha gene polymorphism with both type 1 and type 2 diabetes in a Caucasian (Hungarian) sample

Geza Nagy1, Reka Kovacs-Nagy2, Eva Kereszturi2, Aniko Somogyi1, Anna Szekely3, Nora Nemeth2, Nora Hosszufalusi4, Pal Panczel4, Zsolt Ronai2 and Maria Sasvari-Szekely2*

Author Affiliations

1 2nd Department of Internal Medicine, Semmelweis University, H-1444 Budapest, POB 260, Hungary

2 Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary

3 Department of Psychology, Eötvös Loránd University, Budapest, Hungary

4 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary

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BMC Medical Genetics 2009, 10:79  doi:10.1186/1471-2350-10-79

Published: 19 August 2009



Hypoxia 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.


A 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)


As 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.


We 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.