Candidate Genes for Late Diabetic Complications
Author
Summary, in English
The aim of this study was to
1) To test the usefulness of the new WHO criteria for clinical staging of diabetes in the characterization of diabetic patients.
2) To test a putative association between late diabetic complications and candidate gene polymorphisms.
In study I we could show that the WHO clinical staging of diabetes could discriminate between clinically meaningful subgroups. The IRC patients represented a group with more severe diabetes than acknowledged in the etiological classification with high frequency of diabetic complications. In study II we demonstrated that polymorphisms in the UCP1-3 genes did not play a major role in the development of micro- or macroalbuminuria in Scandinavian diabetic patients. In study III we showed that a polymorphism in the MHC class II transactivator gene (MHC2TA) was associated with cardiovascular mortality and predictors of cardiovascular mortality, microalbuminuria and metabolic syndrome. In study IV and V we showed that polymorphisms in the LTA, TNF and AGER genes were associated with diabetic complications. The association was complex and dependent on the HLA-DQB1 genotypes, with partly different alleles conferring susceptibility in type 1 and type 2 diabetic patients. We cannot exclude that these genes are a part of a large haplotype block that also includes HLA-DQB1 risk genotypes.
Although this study revealed several associations with putative candidate gene polymorphisms and diabetic complications, the studied polymorphisms can only explain part of the genetic riskfactors for diabetic complications. More studies are needed to enable mapping of the susceptibility genes for diabetic complications. Revealing the genetic riskfactors could help us to identify the patients at risk and understand the pathogenesis of diabetic complications and making it possible to find novel treatments for diabetic complications.
Department/s
Publishing year
2007
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2007:147
Full text
Document type
Dissertation
Publisher
Endocrinology
Topic
- Endocrinology and Diabetes
Keywords
- TNF
- sekretion
- LTA
- Endocrinology
- nephropathy
- diabetes mellitus
- retinopathy
- neuropathy
- genetic
- UCP
- diabetologi
- AGER
- MHc2TA
- HLA-DQB1
- Endokrinologi
- secreting systems
- diabetology
Status
Published
Research group
- Genomics, Diabetes and Endocrinology
Supervisor
- Carl-David Agardh
- Leif Groop
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-85897-25-4
Defence date
4 December 2007
Defence time
09:15
Defence place
CRC Aula, ing 72 UMAS, Malmö
Opponent
- Knut Borch-Johnsen (Professor)