title: Association of hypoxia inducible factor-1 alpha gene polymorphism with both type 1 and type 2 diabetes in a Caucasian (Hungarian) sample.
abstract: BACKGROUND
  Hypoxia inducible factor-1 alpha (HIF-1alpha) 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-1alpha 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.
  
  
  METHODS
  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)
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  We confirmed the protective effect of a rare genetic variant of HIF-1alpha 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.
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. ngeza@bel2.sote.hu
authors.forename: Geza
authors.initials: G
authors.lastname: Nagy
authors.forename: Reka
authors.initials: R
authors.lastname: Kovacs-Nagy
authors.forename: Eva
authors.initials: E
authors.lastname: Kereszturi
authors.forename: Aniko
authors.initials: A
authors.lastname: Somogyi
authors.forename: Anna
authors.initials: A
authors.lastname: Szekely
authors.forename: Nora
authors.initials: N
authors.lastname: Nemeth
authors.forename: Nora
authors.initials: N
authors.lastname: Hosszufalusi
authors.forename: Pal
authors.initials: P
authors.lastname: Panczel
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Ronai
authors.forename: Maria
authors.initials: M
authors.lastname: Sasvari-Szekely
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D054458:Amplified Fragment Length Polymorphism Analysis; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006814:Hungary; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014162:Transfection; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
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