Impact of the PPARGC1A Gly482Ser polymorphism on left ventricular structural and functional abnormalities in patients with hypertension.
The Gly482Ser polymorphism in the peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1A) has been reported to contribute to the development of left ventricular (LV) hypertrophy. Little is known, however, about its possible impact on cardiac dysfunction. Enhanced myocardial fibrosis accompanying increased LV mass might represent a link with coexisting functional abnormalities. We investigated the association between the PPARGC1A Gly482Ser polymorphism and LV morphology and performance in essential hypertension, with special consideration of fibrosis intensity. A total of 205 hypertensive patients (60±8 years) underwent echocardiography with assessment of cardiac morphology, LV systolic (strain and strain rate) and diastolic function (peak early diastolic mitral flow velocity/peak late diastolic mitral flow velocity (E/A) ratio, peak early diastolic myocardial velocity (Em), and E/e' ratio (where e' is the peak early diastolic mitral annular velocity)), evaluation of serum procollagen type III amino-terminal propeptide (PIIINP) and procollagen type I carboxy-terminal propeptide (PICP)-markers of fibrosis and the PPARGC1A Gly482Ser genotyping. Subjects with the Ser-Ser genotype demonstrated more profound LV hypertrophy and diastolic function impairment, and higher PICP/PIIINP than the Ser-Gly and Gly-Gly groups. In multivariable analysis, the presence of the Ser-Ser allele was an independent correlate of E/e' (β=0.17, P<0.02), Em (β=-0.18, P<0.01) and LV mass index (β=0.28, P<0.001). In conclusion, in hypertensive patients, the PPARGC1A Gly482Ser polymorphism is associated with LV hypertrophy and diastolic dysfunction, with the presence of the Ser-Ser allele promoting these abnormalities. One of the possible mechanisms mediating the adverse effect on diastolic performance might be a relative increase in the anabolism of rigid collagen type I over that of the more elastic collagen type III, as indicated by an increased ratio of PICP to PIIINP.
Department of Cardiology, Wroclaw Medical University, Wroclaw, Poland.
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Rojek
Department of Cardiology, Wroclaw Medical University, Wroclaw, Poland.
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Cielecka-Prynda
Department of Cardiology, Wroclaw Medical University, Wroclaw, Poland.
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Przewlocka-Kosmala
Department of Endocrinology and Diabetology, Wroclaw Medical University, Wroclaw, Poland.
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Laczmanski
Department of Cardiology, Wroclaw Medical University, Wroclaw, Poland.
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Mysiak
Department of Cardiology, Wroclaw Medical University, Wroclaw, Poland.
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Kosmala
D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D005355:Fibrosis; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D011110:Polymorphism, Genetic; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000235:genetics*; D020257:Ventricular Remodeling / Q000235:genetics*
D015415:Biomarkers; C486497:PPARGC1A protein, human; D010446:Peptide Fragments; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011347:Procollagen; D014157:Transcription Factors; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide