title: Haplotype analysis of the PPARgamma Pro12Ala and C1431T variants reveals opposing associations with body weight.
abstract: BACKGROUND
  Variation at the PPARG locus may influence susceptibility to type 2 diabetes and related traits. The Pro12Ala polymorphism may modulate receptor activity and is associated with protection from type 2 diabetes. However, there have been inconsistent reports of its association with obesity. The silent C1431T polymorphism has not been as extensively studied, but the rare T allele has also been inconsistently linked to increases in weight. Both rare alleles are in linkage disequilibrium and the independent associations of these two polymorphisms have not been addressed.
  
  
  RESULTS
  We have genotyped a large population with type 2 diabetes (n = 1107), two populations of non-diabetics from Glasgow (n = 186) and Dundee (n = 254) and also a healthy group undergoing physical training (n = 148) and investigated the association of genotype with body mass index. This analysis has demonstrated that the Ala12 and T1431 alleles are present together in approximately 70% of the carriers. By considering the other 30% of individuals with haplotypes that only carry one of these polymorphisms, we have demonstrated that the Ala12 allele is consistently associated with a lower BMI, whilst the T1431 allele is consistently associated with higher BMI.
  
  
  CONCLUSIONS
  This study has therefore revealed an opposing interaction of these polymorphisms, which may help to explain previous inconsistencies in the association of PPARG polymorphisms and body weight.
authors.affiliation: Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, Scotland, United Kingdom. alex.doney@tuht.scot.nhs.uk
authors.forename: Alex
authors.initials: A
authors.lastname: Doney
authors.forename: Bettina
authors.initials: B
authors.lastname: Fischer
authors.forename: David
authors.initials: D
authors.lastname: Frew
authors.forename: Alastair
authors.initials: A
authors.lastname: Cumming
authors.forename: David M
authors.initials: DM
authors.lastname: Flavell
authors.forename: Michael
authors.initials: M
authors.lastname: World
authors.forename: Hugh E
authors.initials: HE
authors.lastname: Montgomery
authors.forename: Douglas
authors.initials: D
authors.lastname: Boyle
authors.forename: Andrew
authors.initials: A
authors.lastname: Morris
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
mesh_terms: D000328:Adult; D000409:Alanine / Q000235:genetics* / Q000502:physiology; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics* / Q000502:physiology; D003596:Cytosine / Q000378:metabolism* / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D015444:Exercise / Q000502:physiology; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics* / Q000502:physiology; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D011392:Proline / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000502:physiology; D012044:Regression Analysis; D013941:Thymine / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D003596:Cytosine; D011392:Proline; D000409:Alanine; D013941:Thymine