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Common variants in MODY genes increase the risk of gestational diabetes mellitus.

Shaat, Nael LU ; Ekholm, Ella LU ; Lernmark, Åke LU orcid ; 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)
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author
; ; ; ; ; ; ; and
organization
publishing date
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
2021-09-27 11:50:35
@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},
  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/ws/files/2567802/625504.pdf},
  doi          = {10.1007/s00125-006-0258-8},
  volume       = {49},
  year         = {2006},
}