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

Doney, A S F; Fischer, B; Cecil, J E; Boylan, K; McGuigan, F E LU ; Ralston, S H; Morris, A D and Palmer, C N A (2004) In Diabetologia 47(3). p.555-558
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
keywords
Adult, Amino Acid Substitution, Child, Diabetes Mellitus, Type 2, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Mutation, Missense, PPAR gamma, Polymorphism, Single Nucleotide, Scotland, Journal Article, Research Support, Non-U.S. Gov't
in
Diabetologia
volume
47
issue
3
pages
4 pages
publisher
Springer Verlag
external identifiers
  • scopus:1842866370
ISSN
0012-186X
DOI
10.1007/s00125-003-1323-1
language
English
LU publication?
no
id
dc91378d-10c6-40fa-8379-82fa48b69b34
date added to LUP
2018-01-02 11:11:27
date last changed
2018-12-02 04:57:40
@article{dc91378d-10c6-40fa-8379-82fa48b69b34,
  abstract     = {<p>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.</p><p>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).</p><p>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).</p><p>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.</p>},
  author       = {Doney, A S F and Fischer, B and Cecil, J E and Boylan, K and McGuigan, F E and Ralston, S H and Morris, A D and Palmer, C N A},
  issn         = {0012-186X},
  keyword      = {Adult,Amino Acid Substitution,Child,Diabetes Mellitus, Type 2,Gene Frequency,Genetic Predisposition to Disease,Genetic Variation,Genotype,Humans,Mutation, Missense,PPAR gamma,Polymorphism, Single Nucleotide,Scotland,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {3},
  pages        = {555--558},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes},
  url          = {http://dx.doi.org/10.1007/s00125-003-1323-1},
  volume       = {47},
  year         = {2004},
}