Common variants in MODY genes increase the risk of gestational diabetes mellitus.
Shaat, Nael LU
; Ekholm, Ella
LU
; Lernmark, Åke
LU
; Ivarsson, Sten
LU
; Lynch, Kristian
LU
; Parikh, Hemang
LU
; Almgren, Peter
LU
; Berntorp, Kerstin
LU
and Groop, Leif
LU
(2006)
In Diabetologia
49(7).
p.1545-1551
- Abstract
- Aims/hypothesis Impaired beta cell function is the hallmark of gestational diabetes mellitus (GDM) and MODY. In addition, women with MODY gene mutations often present with GDM, but it is not known whether common variants in MODY genes contribute to GDM.
Subjects and methods We genotyped five common variants in the glucokinase (GCK, commonly known as MODY2), hepatocyte nuclear factor 1-α (HNF1A, commonly known as MODY3) and 4-α (HNF4A commonly known as MODY1) genes in 1,880 Scandinavian women (648 women with GDM and 1,232 pregnant non-diabetic control women).
Results The A allele of the GCK −30G→A polymorphism was more common in GDM women than in control subjects (odds ratio [OR] 1.28 [95% CI 1.06−1.53], p=0.008, corrected... (More) - Aims/hypothesis Impaired beta cell function is the hallmark of gestational diabetes mellitus (GDM) and MODY. In addition, women with MODY gene mutations often present with GDM, but it is not known whether common variants in MODY genes contribute to GDM.
Subjects and methods We genotyped five common variants in the glucokinase (GCK, commonly known as MODY2), hepatocyte nuclear factor 1-α (HNF1A, commonly known as MODY3) and 4-α (HNF4A commonly known as MODY1) genes in 1,880 Scandinavian women (648 women with GDM and 1,232 pregnant non-diabetic control women).
Results The A allele of the GCK −30G→A polymorphism was more common in GDM women than in control subjects (odds ratio [OR] 1.28 [95% CI 1.06−1.53], p=0.008, corrected p value, p=0.035). Under a recessive model [AA vs GA+GG], the OR increased further to 2.12 (95% CI 1.21−3.72, p=0.009). The frequency of the L allele of the HNF1A I27L polymorphism was slightly higher in GDM than in controls (1.16 [95% CI 1.001−1.34], p=0.048, corrected p value, p=0.17). However, the OR increased under a dominant model (LL+IL vs II; 1.31 [95% CI 1.08−1.60], p=0.007). The rs2144908, rs2425637 and rs1885088 variants, which are located downstream of the primary beta cell promoter (P2) of HNF4A, were not associated with GDM.
Conclusions/interpretation The −30G→A polymorphism of the beta-cell-specific promoter of GCK and the I27L polymorphism of HNF1A seem to increase the risk of GDM in Scandinavian women. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/155725
- author
- Shaat, Nael
LU
; Ekholm, Ella
LU
; Lernmark, Åke
LU
; Ivarsson, Sten
LU
; Lynch, Kristian
LU
; Parikh, Hemang
LU
; Almgren, Peter
LU
; Berntorp, Kerstin
LU
and Groop, Leif
LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- GCK, −30G→A, GDM, Genes, Gestationaldiabetes mellitus, Glucokinase, HNF1A, Scandinavian, Polymorphism, HNF4A, I27L, MODY
- in
- Diabetologia
- volume
- 49
- issue
- 7
- pages
- 1545 - 1551
- publisher
- Springer
- external identifiers
-
- wos:000238026100012
- scopus:33744942090
- ISSN
- 1432-0428
- DOI
- 10.1007/s00125-006-0258-8
- language
- English
- LU publication?
- yes
- id
- 8676925d-f649-4591-bc39-35cbc3a7e748 (old id 155725)
- date added to LUP
- 2016-04-01 11:37:45
- date last changed
- 2024-06-17 14:36:33
@article{8676925d-f649-4591-bc39-35cbc3a7e748,
abstract = {{Aims/hypothesis Impaired beta cell function is the hallmark of gestational diabetes mellitus (GDM) and MODY. In addition, women with MODY gene mutations often present with GDM, but it is not known whether common variants in MODY genes contribute to GDM.<br/><br>
Subjects and methods We genotyped five common variants in the glucokinase (GCK, commonly known as MODY2), hepatocyte nuclear factor 1-α (HNF1A, commonly known as MODY3) and 4-α (HNF4A commonly known as MODY1) genes in 1,880 Scandinavian women (648 women with GDM and 1,232 pregnant non-diabetic control women).<br/><br>
Results The A allele of the GCK −30G→A polymorphism was more common in GDM women than in control subjects (odds ratio [OR] 1.28 [95% CI 1.06−1.53], p=0.008, corrected p value, p=0.035). Under a recessive model [AA vs GA+GG], the OR increased further to 2.12 (95% CI 1.21−3.72, p=0.009). The frequency of the L allele of the HNF1A I27L polymorphism was slightly higher in GDM than in controls (1.16 [95% CI 1.001−1.34], p=0.048, corrected p value, p=0.17). However, the OR increased under a dominant model (LL+IL vs II; 1.31 [95% CI 1.08−1.60], p=0.007). The rs2144908, rs2425637 and rs1885088 variants, which are located downstream of the primary beta cell promoter (P2) of HNF4A, were not associated with GDM.<br/><br>
Conclusions/interpretation The −30G→A polymorphism of the beta-cell-specific promoter of GCK and the I27L polymorphism of HNF1A seem to increase the risk of GDM in Scandinavian women.}},
author = {{Shaat, Nael and Ekholm, Ella and Lernmark, Åke and Ivarsson, Sten and Lynch, Kristian and Parikh, Hemang and Almgren, Peter and Berntorp, Kerstin and Groop, Leif}},
issn = {{1432-0428}},
keywords = {{GCK; −30G→A; GDM; Genes; Gestationaldiabetes mellitus; Glucokinase; HNF1A; Scandinavian; Polymorphism; HNF4A; I27L; MODY}},
language = {{eng}},
number = {{7}},
pages = {{1545--1551}},
publisher = {{Springer}},
series = {{Diabetologia}},
title = {{Common variants in MODY genes increase the risk of gestational diabetes mellitus.}},
url = {{https://lup.lub.lu.se/search/files/2567802/625504.pdf}},
doi = {{10.1007/s00125-006-0258-8}},
volume = {{49}},
year = {{2006}},
}