A single nucleotide polymorphism on exon-4 of the gene encoding PPARδ is associated with reduced height in adults and children

Lindsay R. Burch, Kaixin Zhou, Louise A. Donnelly, Alex S F Doney, Jeffrey Brady, Catharine Goddard, Andrew D. Morris, Michael K. Hansen, Colin N A Palmer

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Context: Peroxisome proliferator-activated receptor (PPAR)-δ 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 PPARδ (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 × 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 PPARδ in critical metabolic functions. PPARδ may affect height through a variety of mechanisms including altered metabolic efficiency or effects on osteoclast function.

Original languageEnglish
Pages (from-to)2587-2593
Number of pages7
JournalThe Journal of Clinical Endocrinology & Metabolism (JCEM)
Issue number7
Publication statusPublished - 1 Jul 2009


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