Does signal nucleotide polymorphism of RGS2 and ATIR, individually or in combination modulate the response to antihypertensive drugs in resistant hypertensive subjects?

Resistant hypertension is a public health problem, which is due to the interaction between genetic and environmental factors. It represents the severe form of hypertension, so it is necessary to highlight the different genetic factors involved, which can play a major role in this pathology. The aim of our studies is to evaluate the association between the polymorphisms of ATIR A1166C, RGS2 (-638 A/G and -391G/C) gene and resistant hypertension in Moroccan population. And we attempt to analyze and identify potentially interaction genetic markers that modulate the risk of resistant hypertension. The study was conducted in 160 hypertensive cases from Moroccan population: 70 with resistant hypertension (RH) and 90 with well-controlled hypertension (HT). Polymerase chain reaction followed by restriction fragment analysis length was used to identify -1166A/C AT1R, -395G/C and -638A/G RGS2 genotypes. Statistical analysis was performed by SPSS. Our results suggest that, RGS2 (-395 G/C; -638A/G) and ATIR 1166A/C analyzed separately not fond any significant association P 0.05, although the mutants genotypes are more represented among resistant hypertensive patients to controlled hypertensive subjects. While, the study of haplotypes formed by the combination of alleles of the -638A/G polymorphism and the -395G/C polymorphism of the RGS2 gene showed that the risk of developing resistance was multiplied by 47, OR [(95% CI) = 47 (1.5–1422)]; p = 0.02. The interaction between variant alleles at two candidate loci exhibit trending associations with resistant hypertension, AG-AC combination (2.9 (0.8–9.6)), P value = 0.07. Hypertension is a public health problem worldwide. Despite the number of antihypertensive classes used and available, as well as the many recommendations, it remains insufficiently controlled. Identification of genetic influences on resistance to current therapies might also lead to development of new therapeutic targets. However it is important to understand that a single genetic variant may not reveal significant associations with resistant hypertension because their effects may be dependent on gene-gene or gene-environment interactions.