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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.

Shaat, Nael LU ; Lernmark, Åke LU ; Ekholm, Ella LU ; Ivarsson, Sten LU ; Parikh, Hemang LU ; Berntorp, Kerstin LU and Groop, Leif LU (2007) In Diabetologia 50(5). p.972-979
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Polymorphism, Gestational diabetes mellitus, GDM, FOXC2, Association, ADRB3, Adiponectin, PPARG, PPARGC1A, TCF7L2
in
Diabetologia
volume
50
issue
5
pages
972 - 979
publisher
Springer Verlag
external identifiers
  • wos:000245521400011
  • scopus:34147177660
ISSN
1432-0428
DOI
10.1007/s00125-007-0623-2
language
English
LU publication?
yes
id
d8e8194b-5516-45ce-a695-b116cafbb198 (old id 166781)
date added to LUP
2007-07-30 15:55:33
date last changed
2017-07-30 03:30:24
@article{d8e8194b-5516-45ce-a695-b116cafbb198,
  abstract     = {Aims/hypothesis Genetic and epidemiological studies suggest<br/><br>
an association between gestational diabetes mellitus<br/><br>
and type 2 diabetes. Both are polygenic multifactorial<br/><br>
disorders characterised by beta cell dysfunction and insulin<br/><br>
resistance. Our aim was to investigate whether common<br/><br>
genetic variants that have previously been associated with<br/><br>
type 2 diabetes or related phenotypes would also confer risk<br/><br>
for gestational diabetes mellitus.<br/><br>
Materials and methods In 1,881 unrelated pregnant Scandinavian<br/><br>
women (649 women with gestational diabetes<br/><br>
mellitus, 1,232 non-diabetic control subjects) we genotyped<br/><br>
the transcription factor 7-like 2 (TCF7L2 rs7903146),<br/><br>
adiponectin (ADIPOQ +276G&gt;T), peroxisome-proliferator<br/><br>
activated receptor, gamma 2 (PPARG Pro12Ala), PPARGcoactivator,<br/><br>
1 alpha (PPARGC1A Gly482Ser), forkhead box<br/><br>
C2 (FOXC2 −512C&gt;T) and β3-adrenergic receptor<br/><br>
(ADRB3 Trp64Arg) polymorphisms using TaqMan allelic<br/><br>
discrimination assay or RFLP.<br/><br>
Results The CC, CT and TT genotype frequencies of the<br/><br>
TCF7L2 rs7903146 variant differed significantly between<br/><br>
women with gestational diabetes mellitus and control<br/><br>
women (46.3, 43.6 and 10.1% vs 58.5, 35.3 and 6.2%,<br/><br>
p=3.7×10−6, corrected p value [Pc] for multiple testing<br/><br>
Pc=2.2×10−5). The T-allele was associated with an<br/><br>
increased risk of gestational diabetes mellitus (odds ratio<br/><br>
1.49 [95% CI 1.28–1.75], p=4.9×10−7 [Pc=2.8×10−6]).<br/><br>
Compared with wild-type CC-genotype carriers, heterozygous<br/><br>
(CT-genotype) and homozygous (TT-genotype) carriers<br/><br>
had a 1.6-fold (95% CI 1.26–1.93, p=3.7×10−5<br/><br>
[Pc=0.0002]) and a 2.1-fold (95% CI 1.41–2.99,<br/><br>
p=0.0001 [Pc=0.0008]) increased risk of gestational diabetes<br/><br>
mellitus, respectively. The other polymorphisms<br/><br>
studied were not significantly associated with gestational<br/><br>
diabetes mellitus (ADIPOQ +276G&gt;T: 1.17 [1.01–1.36],<br/><br>
p=0.039 [Pc=0.23]; PPARG Pro12Ala: 1.06 [0.87–1.29],<br/><br>
p=0.53; PPARGC1A Gly482Ser: 0.96 [0.83–1.10], p=0.54;<br/><br>
FOXC2 −512C&gt;T: 1.01 [0.87–1.16], p=0.94; and ADRB3<br/><br>
Trp64Arg: 1.22 [0.95–1.56], p=0.12).<br/><br>
Conclusions/interpretation The TCF7L2 rs7903146 variant<br/><br>
is associated with an increased risk of gestational diabetes<br/><br>
mellitus in Scandinavian women.},
  author       = {Shaat, Nael and Lernmark, Åke and Ekholm, Ella and Ivarsson, Sten and Parikh, Hemang and Berntorp, Kerstin and Groop, Leif},
  issn         = {1432-0428},
  keyword      = {Polymorphism,Gestational diabetes mellitus,GDM,FOXC2,Association,ADRB3,Adiponectin,PPARG,PPARGC1A,TCF7L2},
  language     = {eng},
  number       = {5},
  pages        = {972--979},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus.},
  url          = {http://dx.doi.org/10.1007/s00125-007-0623-2},
  volume       = {50},
  year         = {2007},
}