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


METHODS
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.


CONCLUSIONS
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 PPARdelta in critical metabolic functions. PPARdelta may affect height through a variety of mechanisms including altered metabolic efficiency or effects on osteoclast function.
Burch
Lindsay R
LR
Biomedical Research Institute, Ninewells Hospital, Dundee DD1-9SY, United Kingdom.
Zhou
Kaixin
K
Donnelly
Louise A
LA
Doney
Alex S F
AS
Brady
Jeffrey
J
Goddard
Catharine
C
Morris
Andrew D
AD
Hansen
Michael K
MK
Palmer
Colin N A
CN
D000328:Adult; D001827:Body Height / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D055106:Genome-Wide Association Study; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D015201:Meta-Analysis as Topic; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology; D047494:PPAR delta / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology
D047494:PPAR delta