TY - JOUR
T1 - A single nucleotide polymorphism on exon-4 of the gene encoding PPARδ is associated with reduced height in adults and children
AU - Burch, Lindsay R.
AU - Zhou, Kaixin
AU - Donnelly, Louise A.
AU - Doney, Alex S F
AU - Brady, Jeffrey
AU - Goddard, Catharine
AU - Morris, Andrew D.
AU - Hansen, Michael K.
AU - Palmer, Colin N A
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=67650227498&partnerID=8YFLogxK
U2 - 10.1210/jc.2009-0392
DO - 10.1210/jc.2009-0392
M3 - Article
C2 - 19383774
AN - SCOPUS:67650227498
SN - 0021-972X
VL - 94
SP - 2587
EP - 2593
JO - The Journal of Clinical Endocrinology & Metabolism (JCEM)
JF - The Journal of Clinical Endocrinology & Metabolism (JCEM)
IS - 7
ER -