PGC-1α Gly482Ser Polymorphism Associates With Hypertension Among Danish Whites

Abstract

Abstract-PGC-1␣ is a coactivator of numerous transcription factors and is expressed in tissues with high energy demands and abundant in mitochondria. It is induced in the myocardium on fasting and physical exercise, and cardiac-specific overexpression stimulates mitochondrial biogenesis in mice. The common Gly482Ser polymorphism of PGC-1␣ has previously shown association with arterial hypertension among Austrian men. Thus, we aimed at investigating this relationship in the Danish white population. The Gly482Ser polymorphism was genotyped in a total of 2562 Danish white subjects using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and a GenoView locked nucleic acid assay (LNA), and the relationships of this variant with blood pressure levels and arterial hypertension were analyzed. Furthermore, we performed a combined analysis of the data from the present study in combination with previously published results. The Ser/Ser genotype was significantly associated with a reduced risk of hypertension and with lower systolic, diastolic, and mean arterial blood pressure levels, predominantly among women. Finally, in a combined analysis using data obtained in both sexes, the Ser/Ser genotype group had an estimated odds ratio of 0.70 (95% confidence interval, 0.56 to 0.86) for hypertension compared with Gly/X carriers (Pϭ0.001). In conclusion, the Ser allele of PGC-1␣ Gly482Ser confers a significantly reduced risk of hypertension in whites. Further studies are needed to elucidate the differential role of this polymorphism in men and women.

Genetic analysis of the estrogen-related receptor α and studies of association with obesity and type 2 diabetes

“…Two-way interaction between variants in ESRRA, PPARGC1A and PPARGC1B was modelled using a general linear model where the parameters for marginal effects were chosen according to the significant findings. 15,16 The epistatic parameter was estimated using the individuals for whom both risk alleles were present.…”

PGC-1α: a potent transcriptional cofactor involved in the pathogenesis of type 2 diabetes

“…This chromosomal region has been associated with basal insulin levels in Pima Indians [90], abdominal subcutaneous fat in the Quebec Family Study [91], high BMI in women of Utah pedigrees [92], obesity indices in Mexican Americans [93] and systolic blood pressure in families from the Netherlands [94]. Diabetes-related phenotypes have also been associated with single-nucleotide polymorphisms or haplotypes at the PPARGC1A locus [95][96][97][98][99][100].…”

PGC1α gene Gly482Ser polymorphism predicts improved metabolic, inflammatory and vascular outcomes following bariatric surgery

“…As a rather prevalent polymorphism, ranging from 20 to 50% in distinct populations, 8,9 the Gly482Ser may be an interesting marker for disease progression and complications, and for the association between distinct diseases or clinical conditions. With the recent increase in the number of obese patients selected for gastric bypass surgery, we asked Figure 1 Graphic representations of the changes in anthropometric, metabolic and inflammatory parameters in Gly/Gly (filled squares) or Gly/Ser þ Ser/Ser (filled circles) patients.…”

“…6 A number of recent studies have shown the association of the most common ppargc1a (gene coding for PGC1a) polymorphism, the Gly482Ser, with diseases such as type 2 diabetes, hypertension, hypercholesterolemia and obesity. [7][8][9] However, no previous study has evaluated the association of this polymorphism with the outcomes of bariatric surgery.…”