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

Nagy Geza, Kovacs Nagy Reka, Eva Kereszturi, A. Somogyi, A. Székely, Nora Nemeth, N. Hosszúfalusi, P. Pánczél, Z. Rónai, M. Sasvári

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Abstract

Background: 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. 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 rarein 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. Conclusion: 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.

Original languageEnglish
Article number79
JournalBMC Medical Genetics
Volume10
DOIs
Publication statusPublished - Aug 19 2009

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Hypoxia-Inducible Factor 1
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Genotype
Single Nucleotide Polymorphism
Restriction Fragment Length Polymorphisms
Genes
Alleles
Population
Cytoprotection
Heterozygote
Gene Frequency
Real-Time Polymerase Chain Reaction
Pancreas
Healthy Volunteers
Transcription Factors
Odds Ratio
Amino Acids
Control Groups

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

@article{981abfbffd0b45a381471a400794da14,
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-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. 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 rarein 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. Conclusion: 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.",
author = "Nagy Geza and Reka, {Kovacs Nagy} and Eva Kereszturi and A. Somogyi and A. Sz{\'e}kely and Nora Nemeth and N. Hossz{\'u}falusi and P. P{\'a}ncz{\'e}l and Z. R{\'o}nai and M. Sasv{\'a}ri",
year = "2009",
month = "8",
day = "19",
doi = "10.1186/1471-2350-10-79",
language = "English",
volume = "10",
journal = "BMC Medical Genetics",
issn = "1471-2350",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Association of hypoxia inducible factor-1 alpha gene polymorphism with both type 1 and type 2 diabetes in a Caucasian (Hungarian) sample

AU - Geza, Nagy

AU - Reka, Kovacs Nagy

AU - Kereszturi, Eva

AU - Somogyi, A.

AU - Székely, A.

AU - Nemeth, Nora

AU - Hosszúfalusi, N.

AU - Pánczél, P.

AU - Rónai, Z.

AU - Sasvári, M.

PY - 2009/8/19

Y1 - 2009/8/19

N2 - Background: 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. 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 rarein 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. Conclusion: 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.

AB - Background: 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. 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 rarein 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. Conclusion: 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.

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DO - 10.1186/1471-2350-10-79

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SN - 1471-2350

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