8adbde8d-e5b5-4c58-8905-353deb03df8d
title
Association of the  Pro12Ala  and  C1431T  1431T  variants of  PPARG  and their haplotypes with susceptibility to Type 2 diabetes.
f8374098-8b9c-4502-85fe-b431315678b7
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.