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Diabetologia

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01.05.2007 | Article

A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus

verfasst von: N. Shaat, Å. Lernmark, E. Karlsson, S. Ivarsson, H. Parikh, K. Berntorp, L. Groop

Erschienen in: Diabetologia | Ausgabe 5/2007

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Abstract

Aims/hypothesis

Genetic and epidemiological studies suggest an association between gestational diabetes mellitus and type 2 diabetes. Both are polygenic multifactorial disorders characterised by beta cell dysfunction and insulin resistance. Our aim was to investigate whether common genetic variants that have previously been associated with type 2 diabetes or related phenotypes would also confer risk for gestational diabetes mellitus.

Materials and methods

In 1,881 unrelated pregnant Scandinavian women (649 women with gestational diabetes mellitus, 1,232 non-diabetic control subjects) we genotyped the transcription factor 7-like 2 (TCF7L2 rs7903146), adiponectin (ADIPOQ +276G > T), peroxisome-proliferator activated receptor, gamma 2 (PPARG Pro12Ala), PPARG-coactivator, 1 alpha (PPARGC1A Gly482Ser), forkhead box C2 (FOXC2 −512C > T) and β3-adrenergic receptor (ADRB3 Trp64Arg) polymorphisms using TaqMan allelic discrimination assay or RFLP.

Results

The CC, CT and TT genotype frequencies of the TCF7L2 rs7903146 variant differed significantly between women with gestational diabetes mellitus and control women (46.3, 43.6 and 10.1% vs 58.5, 35.3 and 6.2%, p = 3.7 × 10⁻⁶, corrected p value [Pc] for multiple testing Pc = 2.2 × 10⁻⁵). The T-allele was associated with an increased risk of gestational diabetes mellitus (odds ratio 1.49 [95% CI 1.28–1.75], p = 4.9 × 10⁻⁷ [Pc = 2.8 × 10⁻⁶]). Compared with wild-type CC-genotype carriers, heterozygous (CT-genotype) and homozygous (TT-genotype) carriers had a 1.6-fold (95% CI 1.26–1.93, p = 3.7 × 10⁻⁵ [Pc = 0.0002]) and a 2.1-fold (95% CI 1.41–2.99, p = 0.0001 [Pc = 0.0008]) increased risk of gestational diabetes mellitus, respectively. The other polymorphisms studied were not significantly associated with gestational diabetes mellitus (ADIPOQ +276G > T: 1.17 [1.01–1.36], p = 0.039 [Pc = 0.23]; PPARG Pro12Ala: 1.06 [0.87–1.29], p = 0.53; PPARGC1A Gly482Ser: 0.96 [0.83–1.10], p = 0.54; FOXC2 −512C > T: 1.01 [0.87–1.16], p = 0.94; and ADRB3 Trp64Arg: 1.22 [0.95–1.56], p = 0.12).

Conclusions/interpretation

The TCF7L2 rs7903146 variant is associated with an increased risk of gestational diabetes mellitus in Scandinavian women.

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Titel: A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus
verfasst von: N. Shaat
Å. Lernmark
E. Karlsson
S. Ivarsson
H. Parikh
K. Berntorp
L. Groop
Publikationsdatum: 01.05.2007
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 5/2007
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-007-0623-2

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A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus

Abstract

Aims/hypothesis

Materials and methods

Results

Conclusions/interpretation

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