This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Google Scholar Articles by Burch, L. R. Articles by Palmer, C. N. A. PubMed PubMed Citation Articles by Burch, L. R. Articles by Palmer, C. N. A. Related Collections Pediatric Endocrinology

A Single Nucleotide Polymorphism on Exon-4 of the Gene Encoding PPAR Is Associated with Reduced Height in Adults and Children

Biomedical Research Institute (L.R.B., K.Z., L.A.D., A.S.F.D., A.D.M., C.N.A.P.), Ninewells Hospital, University of Dundee, and Translational Medicine Research Colaboration (J.B., C.G.) DD1-9SY, Dundee, U.K.; and Wyeth Research (M.K.H.), Collegeville, Pennsylvania 19426

Address all correspondence and requests for reprints to: Colin N. A. Palmer, Biomedical Research Institute, Ninewells Hospital and Medical School, Dundee DD1-9SY, United Kingdom. E-mail: colin.palmer{at}cancer.org.uk.

Context: Peroxisome proliferator-activated receptor (PPAR)- is a nuclear transcription factor that plays a key role in many metabolic processes, including energy metabolism, and lipid and glucose metabolism. Candidate gene studies have identified a putative functional variant, rs2016520, in the gene encoding PPAR (PPARD), which is associated in some studies with metabolic traits. In addition, this single-nucleotide polymorphism was associated with adult height in several whole-genome scans, but this association did not achieve whole genome significance.

Objective: This study sought to determine whether PPARD variation influenced height.

Design: Haplotype tagging analysis across PPARD was performed in about 11,000 individuals from the Wellcome Trust U.K. Type 2 Diabetes Case Control Collection (Go-DARTS2).

Results: There was an association between rs2016520 and height in both patients with type 2 diabetes and controls without diabetes (combined P = 5 x 10^–5). In a metaanalysis using published data from Caucasian cohorts totaling more than 38,000 participants, compelling evidence was found for this locus and its association with height (P = 10^–8) with an overall effect size of about 0.5 cm per allele. A similar analysis in a group of 2700 prepubescent children also displayed a similar effect size to that seen in the adults.

Conclusion: PPARD variation is clearly associated with a phenotype of reduced stature in both adults and children. Because height is an important indicator of metabolic and nutritional status, this provides additional support for a key role for PPAR in critical metabolic functions. PPAR may affect height through a variety of mechanisms including altered metabolic efficiency or effects on osteoclast function.

This article has been cited by other articles:

				C. N.A. Palmer Novel Insights Into the Etiology of Diabetes From Genome-Wide Association Studies Diabetes, November 1, 2009; 58(11): 2444 - 2447. [Full Text] [PDF]