Genes predisposing to type 2 diabetes and cardiovascular mortality
Author
Summary, in English
The minimal promoter of GYS1 was identified and the transcriptional activity of the promoter was negatively regulated by forskolin whereas no effect of short time treatment with insulin was observed. The XbaI polymorphism in GYS1 was associated with an increased risk for cardiovascular mortality in males, an effect modulated by the level of physical activity, whereas variants in APOE increased the risk for cardiovascular mortality in females. In morbidly obese subjects, adiponectin serum levels correlated with visceral APM1 expression and carriers of the APM1 G276T G-allele had lower expression of adiponectin mRNA in visceral adipose tissue as well as a higher fat percent than non-carriers. Survival analyses revealed that variations in APM1 (G276T) and PPARG (Pro12Ala), and in particular a combination of risk genotypes of these two polymorphisms were associated with an increased risk for cardiovascular mortality in T2D patients. Increasing the knowledge of gene regulation and expression as well as of how an individual's genetic background determines disease susceptibility and how the individual will respond to environmental factors might in the future lead to more specific and individually accustomed treatments of T2D and CVD.
Department/s
Publishing year
2006
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2006:107
Document type
Dissertation
Publisher
Department of Clinical Sciences, Lund University
Topic
- Endocrinology and Diabetes
Keywords
- APOE
- APM1
- PPARG
- PPARGC1A
- survival abalysis
- Medicin (människa och djur)
- Medicine (human and vertebrates)
- Type 2 Diabetes
- cardiovascular mortality
- glycogen synthase
- adiponectin
- GYS1
Status
Published
Research group
- Genomics, Diabetes and Endocrinology
Supervisor
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 91-85559-31-8
Defence date
29 September 2006
Defence time
09:15
Defence place
Medical Research Centre(Jubileumsaulan Malmö University Hospital, entrance 59
Opponent
- Markku Laakso (Professor)