Peroxisome proliferator-activated receptor-delta genotype influences metabolic phenotype and may influence lipid response to statin therapy in humans: a genetics of diabetes audit and research Tayside study.
BACKGROUND
Previous studies have identified a single-nucleotide polymorphism in the gene encoding peroxisome proliferator-activated receptor-delta (PPARD), rs2016520, that is associated with changes in metabolic disease in some but not all studies, which suggests that PPARD agonists may have therapeutic benefits for the treatment of metabolic disorders, including dyslipidemia, type 2 diabetes, and obesity.


OBJECTIVE
The objective of the study was to determine whether rs2016520 or other single-nucleotide polymorphism in the PPARD locus influenced the risk of developing various characteristics of metabolic disease.


METHODS
Haplotype tagging analysis across PPARD was performed in 11,074 individuals from the Welcome Trust U.K. Type 2 Diabetes Case Control Collection.


RESULTS
In subjects with and without type 2 diabetes, rs2016520 was associated with body mass index, high-density lipoprotein cholesterol, leptin, and TNFalpha and was dependent on gender.


CONCLUSIONS
The current results suggest differential effects of PPARdelta in males and females.
Burch
Lindsay R
LR
Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Angus, Dundee, United Kingdom DD1 9SY. nuclear-receptor@dundee.ac.uk
Donnelly
Louise A
LA
Doney
Alex S F
AS
Brady
Jeffrey
J
Tommasi
Anna M
AM
Whitley
Adrian L
AL
Goddard
Catharine
C
Morris
Andrew D
AD
Hansen
Michael K
MK
Palmer
Colin N A
CN
D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000235:genetics*; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D047494:PPAR delta / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
D052242:Adiponectin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020738:Leptin; D008055:Lipids; D047494:PPAR delta; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol