Examining the relationships between the Pro12Ala variant in PPARG and Type 2 diabetes-related traits in UK samples.
OBJECTIVE
The Pro12Ala polymorphism in the PPARG gene alters amino acid sequence and has shown consistent association with susceptibility to Type 2 diabetes in several populations. The present study makes use of large, well-characterized case-control resources to enhance understanding of this susceptibility effect by examining related traits, such as body mass index (BMI), waist-hip ratio and age at diagnosis.


METHODS
The Pro12Ala variant was genotyped in two UK case samples, ascertained for positive family history and/or early onset of Type 2 diabetes (combined n=971); and in 1257 ethnically matched control subjects.


RESULTS
There were significant associations of the Pro12Ala single nucleotide polymorphism (SNP) genotypes with diabetes in both case-control comparisons (P=0.025 and P=0.039). Comparing individuals homozygous for the Pro allele, with those carrying an Ala allele, the combined odds ratio for diabetes was 1.40 (95% CIs, 1.12-1.76, P=0.0031). There was no association between the variant and either waist-hip ratio or age at diagnosis. Proline homozygosity was associated with increased BMI in one patient group (P=0.013) and decreased BMI in the other (P=0.038).


CONCLUSIONS
This study confirms that variation within PPARG influences susceptibility to Type 2 diabetes in UK samples. However, the relationship between PPARG variation and BMI is more complex, and studies in much larger sample sets will be required to more precisely characterize the effect of this variant on adiposity.
Zeggini
E
E
Oxford Centre for Diabetes, Endocrinology and Metabolism, Headington, Oxford, UK.
Parkinson
J R C
JR
Halford
S
S
Owen
K R
KR
Walker
M
M
Hitman
G A
GA
Levy
J C
JC
Sampson
M J
MJ
Frayling
T M
TM
Hattersley
A T
AT
McCarthy
M I
MI
D017668:Age of Onset; D000409:Alanine; D019943:Amino Acid Substitution; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D047495:PPAR gamma / Q000235:genetics*; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D006113:United Kingdom
D047495:PPAR gamma; D000409:Alanine