تأثير تعدد الأشكال الجينية للأنجيوتنسينوجين (M235T) ومستقبلات الأنجيوتنسين II (A1166C) على الاستجابة لمانع مستقبلات الأنجيوتنسين (كانديسارتان) في مرضى ارتفاع ضغط الدم في محافظة كربلاء

Effect of angiotensinogen (M235T) and angiotensin II type 1 receptor (A1166C) genes polymorphisms on response to angiotensin receptor blocker (candesartan) in hypertensive patients of Karbala province

Abstract

Background: Hypertension is one of the most studied subjects in the previous century. Since genetics play a role in hypertension, pharmacogenetic is used to apply the knowledge of genetic predictors on the treatment and the response to blood pressure-lowering drugs in order to ascertain the genetic determinants of drug efficacy and toxicity prior to initiating therapy. Objective: To study the effect of angiotensinogen gene polymorphism (M235T) and angiotensin II type1 receptor gene polymorphism (A1166C) on response to angiotensin receptor blocker (candesartan) in hypertensive patients of Karbala province.
Patients and Methods: Ninety-two patients with essential hypertension taking 8 mg/day candesartan for not less than six months were recruited for the investigation from Imam Hussein medical city and from private clinic in Karbala province, Iraq. Blood pressure, heart rate and echocardiography reports were recorded. The kidney function tests (serum creatinine and urea) and other biochemical parameters such as angiotensinogen, angiotensin II levels and some electrolytes were analyzed. The tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was used for genotyping of the single nucleotide polymorphisms (M235T and A1166C).
Results: The distribution of M235T SNP among hypertensive patients was 39.13% AA, 21.74% AG and 39.13% GG. While the distribution of A1166C SNP was 54.35% AA, 40.22% AC and 5.43% CC. Regarding echocardiogram (Echo) parameters, the M235T SNP and left ventricular hypertrophy (LVH) had a statistically significant association (p<0.05). Patients with GG genotype had significantly higher proportion (29.34 %) among the patients who have LVH, while patients with AA and AG genotypes had the proportion of 26.08% and 15.21% respectively. On the other hand, there was no statistical association between A1166C and echocardiogram parameters or blood pressure (Bp) parameters (P>0.05) except heart rate; patients with AA genotype have higher heart rate (88.32±10.64, P=0.005) than patients with AC and CC genotype. There was no statistically significant association (P>0.05) between M235T or A1166C SNPs and the kidney function and other biochemical parameters.

Conclusion: Hypertensive patients who have the homozygous mutant type (GG) of M235T in angiotensinogen gene have higher incidence of having hypertension complications LVH, while AG genotype may have protective effect against LVH. The A1166C SNP has neither an effect on hypertension complications nor has an effect on the patients’ response to candesartan in Iraqi hypertensive patients.