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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.

Author:
  • Nael Shaat
  • Åke Lernmark
  • Ella Ekholm
  • Sten Ivarsson
  • Hemang Parikh
  • Kerstin Berntorp
  • Leif Groop
Publishing year: 2007
Language: English
Pages: 972-979
Publication/Series: Diabetologia
Volume: 50
Issue: 5
Document type: Journal article
Publisher: Springer

Abstract english

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), PPARGcoactivator,

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.

Keywords

  • Endocrinology and Diabetes
  • Polymorphism
  • Gestational diabetes mellitus
  • GDM
  • FOXC2
  • Association
  • ADRB3
  • Adiponectin
  • PPARG
  • PPARGC1A
  • TCF7L2

Other

Published
  • Genomics, Diabetes and Endocrinology
  • Diabetes and Celiac Unit
  • Paediatric Endocrinology
  • ISSN: 1432-0428
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00