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The genetic background of gestational diabetes mellitus

Papadopoulou, Anastasia LU (2011) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2011:37.
Abstract
The aims of this work is to better determine the genetic background of gestational diabetes (GDM) and to examine how specific genes affect the development of diabetes post partum.

In the DiPiS (Diabetes Prediction in Skåne) study we typed for HLA-DQB1 alleled, the transcription factor 7-like 2(TCF7L2) rs7903146, rs12255372 and rs7901695 SNPs, the 1858 C>T SNP of the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene and we tested for the presence of islet cell autoantibodies against glutamic acid decarboxylase 65 (GAD65), insulinoma-associated antigen 2 (IA-2) and insulin in women who had been diagnosed with GDM at least once during 2000-2004.

The HLA-DQB1*0602 allele which is considered to be protective for... (More)
The aims of this work is to better determine the genetic background of gestational diabetes (GDM) and to examine how specific genes affect the development of diabetes post partum.

In the DiPiS (Diabetes Prediction in Skåne) study we typed for HLA-DQB1 alleled, the transcription factor 7-like 2(TCF7L2) rs7903146, rs12255372 and rs7901695 SNPs, the 1858 C>T SNP of the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene and we tested for the presence of islet cell autoantibodies against glutamic acid decarboxylase 65 (GAD65), insulinoma-associated antigen 2 (IA-2) and insulin in women who had been diagnosed with GDM at least once during 2000-2004.

The HLA-DQB1*0602 allele which is considered to be protective for type 1 diabetes had a negative association with GDM even when excluding the autoantibody positive GDM women. There was a positive association between the type 2 diabetes associated TCF7L2 and GDM, regardless of the presence of islet cell autoantibodies or of HLA-DQB1*0602. The 1858 C>T SNP of the PTPN22 gene, which is considered a risk SNP for type 1 diabetes as well as other autoimmune disorders, had no association with GDM.

The HLA-DQB1*0602 had even a negative association with diabetes post partum in a group of GDM women diagnosed during 2003-2005 in the Mamma study in which we had follow-up data one to two years after delivery.

We conclude that GDM is a heterogeneous disorder which shares clinical features and genetic predisposition with both type 1 and type 2 diabetes. This is strengthened by the fact that GDM women have an increased risk to develop type 2 or even type 1 diabetes years after delivery. (Less)
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author
supervisor
opponent
  • Prof. Berne, Christian, Uppsala University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Gestational diabetes mellitus, HLA, TCF7L2, PTPN22, Post partum diabetes, Type 1 Diabetes, Type 2 Diabetes, Islet Cell Autoantibodies
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2011:37
pages
154 pages
publisher
Dept of Diabetes and Celiac Disease
defense location
Medicin aula, ing.35, SUS, Malmö
defense date
2011-05-06 09:00
ISSN
1652-8220
ISBN
978-91-86671-85-3
language
English
LU publication?
yes
id
67c01775-c019-4591-83e5-efe8762e8876 (old id 1894715)
date added to LUP
2011-04-19 14:17:47
date last changed
2016-09-19 08:44:47
@phdthesis{67c01775-c019-4591-83e5-efe8762e8876,
  abstract     = {The aims of this work is to better determine the genetic background of gestational diabetes (GDM) and to examine how specific genes affect the development of diabetes post partum. <br/><br>
In the DiPiS (Diabetes Prediction in Skåne) study we typed for HLA-DQB1 alleled, the transcription factor 7-like 2(TCF7L2) rs7903146, rs12255372 and rs7901695 SNPs, the 1858 C&gt;T SNP of the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene and we tested for the presence of islet cell autoantibodies against glutamic acid decarboxylase 65 (GAD65), insulinoma-associated antigen 2 (IA-2) and insulin in women who had been diagnosed with GDM at least once during 2000-2004. <br/><br>
The HLA-DQB1*0602 allele which is considered to be protective for type 1 diabetes had a negative association with GDM even when excluding the autoantibody positive GDM women. There was a positive association between the type 2 diabetes associated TCF7L2 and GDM, regardless of the presence of islet cell autoantibodies or of HLA-DQB1*0602. The 1858 C&gt;T SNP of the PTPN22 gene, which is considered a risk SNP for type 1 diabetes as well as other autoimmune disorders, had no association with GDM.<br/><br>
The HLA-DQB1*0602 had even a negative association with diabetes post partum in a group of GDM women diagnosed during 2003-2005 in the Mamma study in which we had follow-up data one to two years after delivery.<br/><br>
We conclude that GDM is a heterogeneous disorder which shares clinical features and genetic predisposition with both type 1 and type 2 diabetes. This is strengthened by the fact that GDM women have an increased risk to develop type 2 or even type 1 diabetes years after delivery.},
  author       = {Papadopoulou, Anastasia},
  isbn         = {978-91-86671-85-3},
  issn         = {1652-8220},
  keyword      = {Gestational diabetes mellitus,HLA,TCF7L2,PTPN22,Post partum diabetes,Type 1 Diabetes,Type 2 Diabetes,Islet Cell Autoantibodies},
  language     = {eng},
  pages        = {154},
  publisher    = {Dept of Diabetes and Celiac Disease},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {The genetic background of gestational diabetes mellitus},
  volume       = {2011:37},
  year         = {2011},
}