Associations of PPARGC1A haplotypes with plaque score but not with intima-media thickness of carotid arteries in middle-aged subjects.
OBJECTIVE
Peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha, PPARGC1A) integrates the transcriptional program of mitochondrial biogenesis. Mitochondria are the main source of cellular reactive oxygen species implicated in atherogenesis. We therefore ascertained associations of PPARGC1A polymorphisms with asymptomatic carotid atherosclerosis.


METHODS
Eight single nucleotide polymorphisms tagging two haplotype blocks within PPARGC1A were studied in 1379 participants of the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk. Early atherosclerosis was assessed by intima-media thickness and extent of plaques (B-score) of the carotid arteries.


RESULTS
No associations of carotid artery intima-media thickness measurements with block 1 or 2 haplotype distributions or individual haplotypes were observed. However, the block 1 haplotype carrying the variant C nucleotide at -3974 relative to the transcription start site was associated with disease status defined by the presence of more than one minimal lesion and the -3974 C allele was associated with decreased risk (odds ratio=0.60, P=0.007) after adjustment for linkage disequilibrium between single nucleotide polymorphisms.


CONCLUSIONS
These result are consistent with the concept that risk factors for distinct carotid phenotypes may vary and suggest, but do not prove, that PGC-1alpha may contribute to the regulation of atherogenic pathways.
Iglseder
Bernhard
B
Paracelsus Private Medical University, Salzburg.
Oberkofler
Hannes
H
Felder
Thomas K
TK
Klein
Kerstin
K
Paulweber
Bernhard
B
Krempler
Franz
F
Tregouet
David A
DA
Patsch
Wolfgang
W
D000368:Aged; D000483:Alleles; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D016893:Carotid Stenosis / Q000000981:diagnostic imaging* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D017540:Tunica Media / Q000000981:diagnostic imaging*; D014463:Ultrasonography
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors