A single nucleotide polymorphism on Exon-4 of the gene encoding PPAR delta is associated with reduced height inadults 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

    13 Citations (Scopus)


    Context: Peroxisome proliferator-activated receptor (PPAR)-delta 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 delta ( 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 delta in critical metabolic functions. PPAR delta may affect height through a variety of mechanisms including altered metabolic efficiency or effects on osteoclast function. (J Clin Endocrinol Metab 94: 2587-2593, 2009)

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




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