Risk of angiotensin - converting enzyme (ACE) gene I/D and g.2350G > A polymorphisms in causing susceptibility to essential hypertension

Background: Essential hypertension is a complex polygenic disorder arising from the interaction of several genes with environmental factors. Of the various physiological pathways affecting the homeostasis of blood pressure, the renin-angiotensin system (RAS) is considered important with angiotensin converting enzyme (ACE) playing a key role in causing susceptibility to hypertension. Objective: Explore the single locus, haplotype and epistasis patterns of two polymorphisms of ACE gene (VD and g.2350G>A) and their contribution in causing risk for essential hypertension. Methods: Two hundred seventy nine hypertensive cases and 200 healthy controls were recruited. Genotype of the ACE I/D polymorphism was determined by PCR and g.2350G>A polymorphism was assessed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) based method. Results: The distribution of genotypes showed a significant association of ACE I/D polymorphism (chi(2) = 7.148, p=0.028), while ACE g.2350G>A polymorphism did not show any such association (chi(2)=0.85, p = 0.65). For ACE I/D and g.2350G>A polymorphisms, genotypic proportions were statistically significant especially in males (p<0.05). The frequency of H1 haplotype with ACE I and G2350 alleles was higher among hypertensives than in normotensives. The analysis for epistatic interaction showed a strong synergistic effect between I/D and g.2350G>A polymorphisms. Conclusion: Our study suggests significant association of allele I of I/D polymorphism and essential hypertension with strong synergism when segregating with allele G of g.2350G>A polymorphism at ACE locus.