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Cardiología Molecular, Instituto de Investigaciones Médicas A Lanari, Universidad de Buenos Aires, Buenos Aires, Argentina
1 CAIDEM, Chacabuco, Pcia de Buenos Aires, Argentina
2 Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
(Requests for offprints should be addressed to C J Pirola; Email: cjpirola{at}lanari.fmed.uba.ar)
Our objective was to search for differences in genotypes of peroxisome proliferator-activated receptor gamma (PPAR
) (Pro12 Ala) and its coactivator PGC-1
(Gly482 Ser) in adolescents harboring features of metabolic syndrome. In a population-based study, we determined medical history, anthropometric variables, biochemical measurements and arterial blood pressures of 934 high-school students of Caucasian origin. We selected 220 adolescents who had systolic or diastolic blood pressures more than the 80th or less than the 20th percentiles based on the previous single set of measurements. One hundred and seventy-five adolescents completed the study and underwent two additional blood pressure measurements on different days, as well as biochemical analysis and genotyping. We found no association between insulin resistance, body mass index (BMI) and leptin levels and PPAR and PGC-1 genotypes. The 12 Ala PPAR allele was associated with increased waist-to-hip ratio (WHR) and carriers seemed to have higher diastolic blood pressure and lower pulse pressure than non-carriers, particularly in the hypertensive and overweight group. Although Ser482 Ser PGC-1 homozygotes had lower WHRs than other PGC-1 genotypes, they were more frequent in the hypertensive group than in the normotensive (44.4 vs 24.5%, P<0.03), so the 482 Ser PGC-1 allele was in our population a risk factor for hypertension independently of WHR, homeostasis model assessment of insulin resistance, BMI and Pro12 Ala PPAR variant (odds ratio=4.0, 95% confidence interval 1.5–10.6, P<0.01). Multiple regression analysis showed that age- and sex-adjusted systolic blood pressure correlated with the 482 Ser PGC-1 allele regardless of those covariates. In conclusion, the Gly482 Ser variant of the PGC-1 gene may be an independent genetic risk factor for young-onset hypertension.
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