Abstract
AimTo explore the role of the ACE gene polymorphisms in the risk of essential hypertension in Mexican Mestizo individuals and evaluate the correlation between these polymorphisms and the serum ACE levels.MethodsNine ACE gene polymorphisms were genotyped by 5′ exonuclease TaqMan genotyping assays and polymerase chain reaction (PCR) in 239 hypertensive and 371 non- hypertensive Mexican individuals. Haplotypes were constructed after linkage disequilibrium analysis. ACE serum levels were determined in selected individuals according to different haplotypes.ResultsUnder a dominant model, rs4291 rs4335, rs4344, rs4353, rs4362, and rs4363 polymorphisms were associated with an increased risk of hypertension after adjusting for age, gender, BMI, triglycerides, alcohol consumption, and smoking. Five polymorphisms (rs4335, rs4344, rs4353, rs4362 and rs4363) were in strong linkage disequilibrium and were included in four haplotypes: H1 (AAGCA), H2 (GGATG), H3 (AGATG), and H4 (AGACA). Haplotype H1 was associated with decreased risk of hypertension, while haplotype H2 was associated with an increased risk of hypertension (OR = 0.77, P = 0.023 and OR = 1.41, P = 0.004 respectively). According to the codominant model, the H2/H2 and H1/H2 haplotype combinations were significantly associated with risk of hypertension after adjusted by age, gender, BMI, triglycerides, alcohol consumption, and smoking (OR = 2.0; P = 0.002 and OR = 2.09; P = 0.011, respectively). Significant elevations in serum ACE concentrations were found in individuals with the H2 haplotype (H2/H2 and H2/H1) as compared to H1/H1 individuals (P = 0.0048).ConclusionThe results suggest that single nucleotide polymorphisms and the “GGATG” haplotype of the ACE gene are associated with the development of hypertension and with increased ACE enzyme levels.
Highlights
Hypertension plays a major etiologic role in the development of cerebrovascular disease, ischemic heart disease, cardiac and renal failure. [1]
angiotensin-converting enzyme (ACE) is a key enzyme in the renin-angiotensin-aldosterone (RAAS) and kalikrein-kinin systems [7,8] playing a crucial role in blood pressure (BP) regulation and electrolyte balance [9]
Tiret et al demonstrated that this polymorphism is in close linkage disequilibrium to at least one, and perhaps more functional polymorphisms determining the phenotypic variations of enzyme levels [11]
Summary
Hypertension plays a major etiologic role in the development of cerebrovascular disease, ischemic heart disease, cardiac and renal failure. [1]. It has been suggested that this polymorphism could explain up to 47% of total phenotypic variation in ACE serum levels and determines ACE enzyme activity [10]. Tiret et al demonstrated that this polymorphism is in close linkage disequilibrium to at least one, and perhaps more functional polymorphisms determining the phenotypic variations of enzyme levels [11]. The role of ACE gene polymorphisms in hypertension has not been studied in the Mexican population. Population LD block differences were observed, as haplotypes were shorter and more diverse in Africans, while Europeans had longer and fewer haplotypes This suggests that different linkage disequilibrium of the polymorphisms located in the ACE gene can be observed in other populations. The objective of the present study was to analyze whether these polymorphisms or given haplotypes are associated with essential hypertension and ACE serum levels in Mexican Mestizo individuals
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