Variation in the peroxisome proliferator-activated receptor delta gene in relation to common metabolic traits in 7,495 middle-aged white people.
OBJECTIVE
Studies in animals reveal that peroxisome proliferator-activated receptor delta (PPARdelta) regulates glucose metabolism and insulin sensitivity in both the liver and skeletal muscles. Moreover, PPARdelta augments physical endurance and increases oxidative metabolism, thereby averting obesity. Thus, we hypothesised that common variation in the PPARD gene is associated with insulin resistance and metabolic traits.


METHODS
We studied variation in the exonic region of PPARD. Based upon the results of variant detection and information derived from the HapMap data resource, we selected common variants and tag single-nucleotide polymorphisms for genotyping in 7,495 white subjects, including 1,416 patients with type 2 diabetes.


RESULTS
Fourteen nucleotide variants were identified and a total of 12 variants capturing the common variation of PPARD were genotyped. In the population-based Inter99 (ClinicalTrials.gov ID no: NCT00289237) sample we observed no robust association with homeostasis model assessment of insulin resistance (HOMA-IR), adiposity measures or fasting serum lipids. Similarly, no association with type 2 diabetes or the metabolic syndrome was found.


CONCLUSIONS
Based on thorough investigation, we conclude that common variation in PPARD does not significantly affect the risk of metabolic disease in the population studied. Given the confidence intervals that were found for effect size estimates, we can effectively rule out an increase in HOMA-IR of any tag SNP above 7% per allele, assuming an additive model. Likewise, we can exclude an odds ratio of type 2 diabetes above 1.27 per allele.
Grarup
N
N
Steno Diabetes Center, Niels Steensens Vej 1, NLC2.14, 2820 Gentofte, Copenhagen, Denmark. ngrp@steno.dk
Albrechtsen
A
A
Ek
J
J
Borch-Johnsen
K
K
Jørgensen
T
T
Schmitz
O
O
Hansen
T
T
Pedersen
O
O
D000328:Adult; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D016678:Genome; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics*; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
D008055:Lipids; D047494:PPAR delta; D005947:Glucose