| Gestational diabetes mellitus is associated with TCF7L2 gene polymorphisms independent of HLA-DQB1*0602 genotypes and islet cell autoantibodies. | |
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MedLine Citation:
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PMID: 21672010 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: To test whether the TCF7L2 gene was associated with gestational diabetes, whether the association between TCF7L2 and gestational diabetes was independent of HLA-DQB1*0602 and islet cell autoantibodies, as well as maternal age, number of pregnancies, family history of diabetes and the HLA-DQB1 genotypes, and to test whether the distribution of HLA-DQB1 alleles was affected by country of birth. METHODS: We genotyped the rs7903146, rs12255372 and rs7901695 single nucleotide polymorphisms of the TCF7L2 gene in 826 mothers with gestational diabetes and in 1185 healthy control subjects in the Diabetes Prediction in Skåne Study. The mothers were also typed for HLA-DQB1 genotypes and tested for islet cell autoantibodies against GAD65, insulinoma-associated antigen-2 and insulin. RESULTS: The heterozygous genotypes CT, GT and TC of the rs7903146 (T is risk for Type 2 diabetes), rs12255372 (T is risk for Type 2 diabetes) and rs7901695 (C is risk for Type 2 diabetes), respectively, as well as the homozygous genotypes TT, TT and CC of the rs7903146, rs12255372 and rs7901695, respectively, were strongly associated with gestational diabetes (P < 0.0001). These associations remained statistically significant after adjusting for maternal age, number of pregnancies, family history of diabetes and HLA-DQ genotypes and were independent of the presence of islet cell autoantibodies. No interaction was observed between TCF7L2 and HLA-DQB1*0602, which was shown to be negatively associated with gestational diabetes in mothers born in Sweden (P = 0.010). CONCLUSIONS: The TCF7L2 was associated with susceptibility for gestational diabetes independently of the presence of HLA-DQB1*0602 and islet cell autoantibodies and other factors such as maternal age, number of pregnancies, family history of diabetes and other HLA-DQ genotypes. The HLA-DQB1*0602 was negatively associated with gestational diabetes in mothers born in Sweden. |
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Authors:
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A Papadopoulou; K F Lynch; N Shaat; R Håkansson; S A Ivarsson; K Berntorp; C D Agardh; Å Lernmark; |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Diabetic medicine : a journal of the British Diabetic Association Volume: 28 ISSN: 1464-5491 ISO Abbreviation: Diabet. Med. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-08-16 Completed Date: 2011-11-02 Revised Date: 2011-12-07 |
Medline Journal Info:
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Nlm Unique ID: 8500858 Medline TA: Diabet Med Country: England |
Other Details:
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Languages: eng Pagination: 1018-27 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK. |
Affiliation:
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Department of Clinical Sciences, Lund University, Malmö, Sweden. Anastasia.Papadopoulou@med.lu.se |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Autoantibodies / genetics* Diabetes, Gestational / genetics*, immunology Female Genetic Predisposition to Disease / genetics* Genotype HLA-DQ Antigens / genetics*, immunology HLA-DQ beta-Chains Humans Islets of Langerhans* Maternal Age Membrane Glycoproteins / genetics*, immunology Parity Polymorphism, Single Nucleotide / genetics Pregnancy Sweden Transcription Factor 7-Like 2 Protein / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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DK26190/DK/NIDDK NIH HHS; R01 DK026190-22/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies; 0/HLA-DQ Antigens; 0/HLA-DQ beta-Chains; 0/HLA-DQB1 antigen; 0/Membrane Glycoproteins; 0/TCF7L2 protein, human; 0/Transcription Factor 7-Like 2 Protein |
| Investigator | |
Investigator/Affiliation:
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A Carlsson / ; E Cederwall / ; C M Cilio / ; B Jönsson / ; H Larsson / ; K Larsson / ; B Lernmark / ; B Lindberg / ; J Neiderud / ; S Resic-Lindehammer / ; S Sjöblad / |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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