Title:

The role of selected polymorphisms of receptor proteins in the pathogenesis of type 2 diabetes, prediabetic quantitative traits and obesity in a Polish population

Author:

Frey, Jakub

Subject:

type 2 diabetes ; PPARgamma ; GLP1 ; gene ; polymorphism

Abstract:

462 unrelated individuals with type 2 diabetes mellitus and 428 healthy volunteers answered a questionnaire, regarding in the diabetes group: age of onset of the disease, its treatment, chronic complications, in both groups: other diseases, use of medication, smoking status, familial history of type 2 diabetes and other medical issues. In all subjects blood was drawn for biochemical and genetic testing. In 305 individuals with normal fasting glycemia an oral glucose tolerance test was performed – those with abnormal glucose tolerance were excluded from further analysis. In all study subjects the genotypes of polymorphisms: Gly168Ser i Phe260Leu in GLP1R gene and Pro12Ala in the PPARγ gene were ascertained. Moreover in individuals from both groups with the BMI >=25 a mutation Pro115Gln in PPARγ was genotyped. Polymorphism Gly168Ser in GLP1R was significantly more frequent among type 2 diabetics (p=0,027 for an additive effect of mutated allele). Stratification analysis showed the relation as being dependent on association present in women p=0,012). In order to investigate the effect of above-mentioned genetic polymorphisms on prediabetic phenotypes in the group of patients with normal glucose tolerance verified in OGTT an analysis of their association with fasting and 120 minutes post-glucose glycemia and insulnemia and insulin sensitivity and secretion indices derived from those measurements was performed. The polymorphism Gly168Ser in the GLP1R gene was significantly associated with lower post-glucose insulinemia (p=0,019) and lower post glucose to fasting insulinemia ratio (p=0,023) as well as with greater Gutt insulin sensitivity index (p=0,034). To conclude, the polymorphism Gly168Ser in the GLP1R gene may confer a risk of type 2 diabetes in women, possibly due to attenuation of incretin effect leading to decreased pancreatic islets β-cells function.

Level of degree:

2 - studia doktoranckie

Degree discipline:

endokrynologia ; genetyka

Degree grantor:

Wydział Lekarski

Promoter:

Jacek Sieradzki

Date:

2008

Date issued:

2007

Type:

Praca doktorska

Format:

application/pdf

Call number:

ZB-107319

ControlNumberVIRTUA:

click here to follow the link

Access rights:

nieograniczony

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego - Collegium Medicum

×

Citation

Citation style: