Gender Specific Association of RAS Gene Polymorphism with Essential Hypertension: A Case-Control Study

Abstract

Renin-angiotensin system (RAS) polymorphisms have been studied as candidate risk factors for hypertension with inconsistent results, possibly due to heterogeneity among various genetic and environmental factors. A case-control association study was conducted to investigate a possible involvement of polymorphisms of three RAS genes: AGT M235T (rs699), ACE I/D (rs4340) and G2350A (rs4343), and AGTR1 A1166C (rs5186) in essential hypertensive patients. A total of 211 cases and 211 controls were recruited for this study. Genotyping was performed using PCR-RFLP method. The genotype and allele distribution of the M235T variant differed significantly in hypertensives and normotensives (OR-CI = 2.62 (1.24–5.76), P = 0.006; OR-CI = 0.699 (0.518–0.943), P = 0.018), respectively. When the samples were segregated based on sex, the 235TT genotype and T allele were predominant in the female patients (OR-CI = 5.68 (1.60-25.10), P = 0.002; OR-CI = 0.522 (0.330–0.826), P = 0.005) as compare to the male patients (OR-CI = 1.54 (1.24–5.76), P = 0.34; OR-CI = 0.874 (0.330–0.826), P = 0.506), respectively. For ACE DD variant, we found overrepresentation of “I”-allele (homozygous II and heterozygous ID) in unaffected males which suggest its protective role in studied population (OR-CI = 0.401 (0.224–0.718); P = 0.0009). The M235T variant of the AGT is significantly associated with female hypertensives and ACE DD variant could be a risk allele for essential hypertension in south India.

Correlation between renin-angiotensin system gene polymorphisms and essential hypertension in the Chinese Yi ethnic group

“…Studies in south Indian also demonstrated the existence of gender-based differences in RAS gene polymorphism. 32 This difference may occur due to the regulation of RAS activity by estrogen and variations in the sensitivity of different alleles to estrogen. Clinically, the prevalence of hypertension in post-menopausal females was found to be much higher than that of pre-menopausal females; estrogen deficiency was the main reason for this difference.…”

Analysis of correlations between coronary heart disease and haplotypes of the angiotensin II receptor type 1 (AGTR1) gene

“…The renin-angiotensin system (RAS) is an important circulatory endocrine network that affects cardiovascular remodeling and maintains water-electrolyte homeostasis (Lis, 1999;Kumar et al, 2008). Polymorphism of RAS genes can affect the pathogenesis of hypertension and CAD, including ischemic heart disease and heart failure (Carluccio et al, 2001;Dhanachandra Singh et al, 2014). Furthermore, angiotensin is a critical component of the RAS and exerts its effects through AGTR1, which is related to vascular lesions.…”

Relationship of renin‐angiotensin system polymorphisms with ambulatory and central blood pressure in patients with hypertension

“…The differences in allele frequency among different ethnic groups are larger, and the same between patients with hypertension and normotension . Several studies have found that among different ethnic groups, locations, and sexes, the A1166c polymorphism may play different roles for essential hypertension . It is worth noting that phenotype‐genotype relationships strongly depend on host factors such as sex, obesity, and lifestyle, in particular salt intake, as reflected by the 24‐hour urinary excretion of sodium .…”