A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus.
Author
Summary, in 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.
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.
Publishing year
2007
Language
English
Pages
972-979
Publication/Series
Diabetologia
Volume
50
Issue
5
Full text
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Document type
Journal article
Publisher
Springer
Topic
- Endocrinology and Diabetes
Keywords
- Polymorphism
- Gestational diabetes mellitus
- GDM
- FOXC2
- Association
- ADRB3
- Adiponectin
- PPARG
- PPARGC1A
- TCF7L2
Status
Published
Research group
- Genomics, Diabetes and Endocrinology
- Celiac Disease and Diabetes Unit
- Paediatric Endocrinology
ISBN/ISSN/Other
- ISSN: 1432-0428