An Association Study Of Renin-Angiotensin System Gene Polymorphisms And Left Ventricular Hypertrophin Essential Hypertension

Backgroud: Left Ventricular Hypertrophy (LVH) is a major independent risk factor for cardiovascular disease. Once LVH occured in patients with essential hypertension (EH), the mortality and morbidity of cardiovascular events increased obviously. Experimental researches indicated that Angiotensinogen II (Ang II) might stimulate cardiovascular remodeling and cardiac hypertrophy. Three key components of Renin-Angiotensin System (RAS) are Angiotensin-Converting Enzyme (ACE), Angiotensinogen (AGT) and Angiotensin II Type 1 Receptor (AT,R), which are mostly involved in generation and making effects of Ang II. Recently, the relationships between RAS gene polymorphisms and EH-LVH were evaluated in many researches. Previously studies have shown a possible association between the insertion/deletion polymorphism of ACE(I/D) gene and EH-LVH. Not only the association between AGT(M235T) or AT,R(A1166C) polymorphism and EH-LVH, but also interactive effects of these genes on LVH in patients with EH are not yet clear.The aims of present study are: To investigate both the separate and interactive effects of three gene polymorphisms on EH-LVH, and to figure out more evidences about genetic susceptibility of RAS gene polymorphisms on EH-LVH further.The major methods include: 1 The gene polymorphism of ACE(I/D) was determined by polymerase chain reaction(PCR) and gene polymorphisms ofAGT(M235T) or AT,R (A1166C) and EH-LVH (p>0.05). (4) There was an association of ACE (I/D) genotype with EH-LVH carrying the AGT-TT genotype (x2 =6.22, p=0.044), as well as the D allele in EH-LVH group was significantly greater than that in EH-non-LVH group carrying the AGT-TT genotype (x2 =6.91, p=0.009). Moreover, the relative risk to LVH increased in these kind of EH patients (OR: 2.50, 95%CI: 1.25-5.00) . (5) No significant differences in the genotype and allele distribution of the ACE (I/DX AGT(M235T) and AT,R (A1166C) were found between the concentric-LVH and eccentric-LVH groups (p>0.05) .In conclusion: This research indicated that: AGT(M235T) T allele was significantly associated with EH in Sichuan Hans population. The D allele of ACE(I/D) may be an independent risk factor for LVH. The synergistic effects of ACE AGT gene polymorphism indicated that D allele of ACE (I/D ) was more susceptibility to LVH carrying AGT-TT genotype by combined genotype analysis. It seems reasonable to make a preliminary conclusion that the interaction effect of multigenes might be more worthy to study than single gene's. There was no evidence to indicate that gene polymorphism of AT,R (A1166C) was involved in EH and EH-LVH in our research, and RAS gene polymorphism might not contribute to left ventricular geometry in EH-LVH.