Genomic Research in Postmenopausal Hypertension

Abstract

Hypertension should be considered a multifactorial phenotype in which genes and environment interact to produce elevated blood pressure (BP). Research in genetics (family or twin studies) demonstrated that hypertension is only moderately heritable.1 A family history of hypertension is associated with four times increased risk of future hypertension.2 By contrast, research in genomics contributed to identify specific genetic variants (single nucleotide polymorphisms [SNPs]) of high penetrance resulting in rare forms of hypertension (eg, Liddle syndrome) in which environmental factors do not play a major role. Common genetic variants of low penetrance separately or in combination with other variants (haplotypes by statistical means) could affect, mostly in a small degree, BP levels along with the "sparring partnership" of adverse environmental factors. It is simply understood that searching genomes to identify single genetic variants or to combine different variants (statistical haplotypes) with meaningful synergistic or additive effects on BP levels is not an easy task to pursue. However, in the latter 10 years, under unbiased investigation, a lot of "genomic decoding" relevant to hypertension has been made in which genetic variants were identified to positively or negatively modulate either BP levels or hypertension trait.3 Of note, occasionally genetic variants are not exclusively related to hypertension but also to other morbidities. For example, peroxisome proliferator-activated receptor (PPAR) c SNPs were related to diabetes mellitus beyond hypertension.In the present issue of The Journal of Clinical Hypertension, Grygiel-G orniak and colleagues 4 evaluated the role of variants of PPAR-c and b3-adrenergic receptors in postmenopausal women free of metabolic disease with and without hypertension in order to investigate whether postmenopausal hypertension has a genetically plausible substrate. The rationale to perform this study 4 was that most studied SNPs were previously investigated separately and not in constellation and mainly in patients with treated metabolic disease (eg, diabetes mellitus and obesity).The distribution of single genetic variants and haplotypes along with studied SNPs were not different between hypertensive and normotensive postmenopausal women. However, hypertensive women were characterized by more impaired metabolic profile measures compared with normotensive patients. Focusing on PPAR-c, increased plasma glucose levels in Pro12Ala polymorphism carriers and higher energy intake in those with C1431T and T1431T both determined the hypertensive phenotype. Moreover, Pro12Pro genotype of PPAR-c was associated with wider pulse pressure, whereas its association with systolic and diastolic BP was not observed.First, taken together, SNPs of b3-adrenergic receptor were not associated with either hypertension or any individual BP component. Second, although the Pro12-Pro variant of PPAR-c determined increased pulse pressure, it had no effect on systolic and diastolic BP. Finally, more impaired gly...