Format

Send to

Choose Destination
Diabetologia. 2004 Mar;47(3):555-558. doi: 10.1007/s00125-003-1323-1. Epub 2004 Jan 17.

Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes.

Author information

1
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK.
2
Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK.
3
Department of Psychology, University of Dundee, Dundee, Scotland, UK.
4
University of Aberdeen Medical School, Institute of Medical Sciences, Aberdeen, Scotland, UK.
5
Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK.
6
Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK. colin.palmer@cancer.org.uk.

Abstract

AIMS/HYPOTHESIS:

The Pro12Ala polymorphism of peroxisome proliferator-activated receptor (PPAR)gamma has been consistently associated with Type 2 diabetes. The rare Ala12 variant is estimated to reduce the risk of developing Type 2 diabetes by 20 percent. This variant is in linkage disequilibrium with another common variant, T1431. Both have opposing associations with body weight. We therefore examined the association of specific haplotypes marked by these two variants with susceptibility to Type 2 diabetes.

METHODS:

We determined the PPARG genotype of a large Scottish cohort of Type 2 diabetic patients ( n=1997) and compared allele frequencies with a cohort of local children ( n=2444) and a middle-aged, population-based cohort from Scotland ( n=1061).

RESULTS:

Frequency of the Ala12 allele was slightly lower in the Type 2 diabetic cohort than in the children [odds ratio (OR)=0.91, p=0.1]. In contrast, the Ala12 variant was under-represented in the Type 2 diabetic population when compared with similarly aged non-diabetic adults (OR=0.74, p=0.0006). When the Ala12 variant was on a haplotype not bearing the 1431T variant, it conferred greater protection (OR=0.66, p=0.003). However, when it was present in haplotypes containing the 1431T variant (70% of Ala12 carriers), this protection was absent (OR=0.99, p=0.94).

CONCLUSIONS/INTERPRETATION:

We replicated the finding that the Ala12 variant of PPARgamma affords protection from Type 2 diabetes, and suggest that this protection is modulated by additional common variation at the PPARG locus.

PMID:
14730381
DOI:
10.1007/s00125-003-1323-1
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center