Angiotensin-converting enzyme insertion/deletion polymorphism in hypertrophic cardiomyopathy: An Egyptian case control study

Hypertrophic Cardiomyopathy (HCM) is a disease characterized by genetic and phenotypic heterogeneity. Renin–angiotensin–aldosteron be system (RAAS) is a potential disease modifier. The aim of the present case control study is evaluation of the controversial role of ACE I/D polymorphism in HCM among Egyptians.Subjects and methods: The study comprised 211 unrelated HCM patients (138 sporadic, 73 familial) and 203 age and sex matched ECG screened healthy volunteers. ACE I/D polymorphism was determined using previously described PCR and gel electrophoresis based method.Results: Distribution of ACE genotype among the Egyptian controls was in Hardy-Weinberg equilibrium (P = 0.778) but not in HCM patients (P = 0.0010). The ACE DD genotype was significantly higher among HCM patients (P = 0.049), particularly in sporadic HCM group compared with familial cases (P = 0.0001). In addition, the distribution of D allele was significantly higher in HCM patients carrying sarcomeric mutations in TNNT2 and MYH7, (P = 0.0476). There was no observed significant effect of the ACE genotypes on the phenotypic expression of the disease.Conclusion: The finding of higher frequency of DD genotype among HCM patients compared to healthy volunteers, particularly so, in sporadic cases suggests that HCM expression is possibly influenced by a genetically predisposed milieu partially determined by the ACE I/D variants. Despite the lack of significant correlation between I/D variants and clinicopathologic characteristics of the HCM patients, however, the higher prevalence of D allele among TNNT2 and MYH7 mutation carriers may contribute to the variable disease outcome among sarcomeric gene positive cases, such a correlation can only be proven through long term follow up studies