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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/166781
- author
- Shaat, Nael
LU
; Lernmark, Åke
LU
; Ekholm, Ella
LU
; Ivarsson, Sten
LU
; Parikh, Hemang
LU
; Berntorp, Kerstin
LU
and Groop, Leif
LU
- organization
- publishing date
- 2007
- 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
- external identifiers
-
- wos:000245521400011
- scopus:34147177660
- ISSN
- 1432-0428
- DOI
- 10.1007/s00125-007-0623-2
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pediatrics/Urology/Gynecology/Endocrinology (013240400), Diabetes and Endocrinology (013241530), Paediatric Endocrinology Research Group (013243010), Diabetes and Celiac Unit (013241540)
- id
- d8e8194b-5516-45ce-a695-b116cafbb198 (old id 166781)
- date added to LUP
- 2016-04-01 11:33:07
- date last changed
- 2024-04-08 05:10:37
@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>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>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>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>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}},
keywords = {{Polymorphism; Gestational diabetes mellitus; GDM; FOXC2; Association; ADRB3; Adiponectin; PPARG; PPARGC1A; TCF7L2}},
language = {{eng}},
number = {{5}},
pages = {{972--979}},
publisher = {{Springer}},
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 = {{https://lup.lub.lu.se/search/files/2540498/625907.pdf}},
doi = {{10.1007/s00125-007-0623-2}},
volume = {{50}},
year = {{2007}},
}