Polymorphisms of the peroxisome proliferator-activated receptor-gamma coactivator-1alpha gene are associated with hypertrophic cardiomyopathy and not with hypertension hypertrophy.
BACKGROUND
The clinical phenotype of both hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) induced by hypertension is heterogeneous. Genetic factors may contribute to this heterogeneity. Evidence is accumulating that the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) gene plays a role in cardiac hypertrophy. The aim of our study was to identify the association between PGC-1alpha gene polymorphisms and cardiac hypertrophy.


METHODS
A total of 270 consecutive HCM patients and 2486 hypertensive patients, comprising 1180 with LVH and 1306 without LVH, as well as 894 healthy controls, were successfully investigated. Polymorphisms of the PGC-1alpha gene were genotyped by PCR-restriction fragment length polymorphism and confirmed by sequencing.


RESULTS
The Ser482 allele (rs8192678 G>A and A>A) and CC genotype of Thr394Thr (rs2970847) conferred increased risk for HCM [odds ratio (OR) 1.52, 95% confidence interval (CI) 1.11-2.11; OR 1.49, 95% CI 1.15-1.98, respectively]. The maximum ventricular thickness was greater in HCM patients carrying the Ser482 risk allele than in carriers of the non-risk allele (20.7+/-4.1 vs. 19.1+/-4.3 mm, p<0.05) and for the CC Thr394Thr genotype (20.9+/-4.6 vs. 19.0+/-4.2 mm, p<0.05). No association was found between PGC-1alpha polymorphism and hypertension with or without LVH.


CONCLUSIONS
Our data indicate that variants of the PGC-1alpha gene are correlated with increased risk for HCM.
Wang
Shuxia
S
Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of the Ministry of Education, Beijing, PR China.
Fu
Chunyan
C
Wang
Hu
H
Shi
Yi
Y
Xu
Xiqi
X
Chen
Jingzhou
J
Song
Xiaodong
X
Sun
Kai
K
Wang
Jianwei
J
Fan
Xiaohan
X
Wang
Hongjian
H
Yang
Xiaomin
X
Huan
Tujun
T
Hui
Rutai
R
D000328:Adult; D000483:Alleles; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011110:Polymorphism, Genetic / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*
D006360:Heat-Shock Proteins; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors