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      Insertion/deletion polymorphism of the angiotensin-converting enzyme gene and the risk of hypertension among residents of two cities, South-South Nigeria

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          Abstract

          Background:

          Hypertension is a public health challenge due to its high prevalence, and is a major risk factor for cardiovascular diseases. This study was designed to determine the frequency of the I/D polymorphism of the angiotensin-converting enzyme gene and its association with hypertension in a sample population of Calabar and Uyo, South-South Nigeria.

          Materials and Methods:

          A population-based case control design consisting of total of 1224 participants, 612 each of patients and controls, were randomly recruited from hypertension clinics and the general population. The I/D polymorphism was investigated using polymerase chain reaction. Multiple regression and odds ratio (OR) was applied to test whether the ID genotypes were predictors of hypertension.

          Results:

          The I/D genotype frequencies were 73(12%), 262(43%) and 277(45%); 74(12%), 303(50%) and 235(38%) for the II, ID, DD genotype in patient and control groups, respectively. A higher frequency of the ID genotype was observed in controls of which 208(61%) were females. By multiple regression analysis, age was a predictor for SBP in patients, r = 0.596, and DBP in controls, r = 0.555. Gender, Body mass index, I/D genotypes were not significant predictors for hypertension but the I/D polymorpism was associated with an increased risk for hypertension with an OR of 1.15 95%CI (0.924-1.456).

          Conclusion:

          The I/D polymorphism of the angiotensin-converting enzyme gene was a risk factor for hypertension in the sample population of Calabar and Uyo. This research will form baseline information for subsequent molecular studies in this population.

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          Most cited references32

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          Evolutionary impact of human Alu repetitive elements.

          Early studies of human Alu retrotransposons focused on their origin, evolution and biological properties, but current focus is shifting toward the effect of Alu elements on evolution of the human genome. Recent analyses indicate that numerous factors have affected the chromosomal distribution of Alu elements over time, including male-driven insertions, deletions and rapid CpG mutations after their retrotransposition. Unequal crossing over between Alu elements can lead to local mutations or to large segmental duplications responsible for genetic diseases and long-term evolutionary changes. Alu elements can also affect human (primate) evolution by introducing alternative splice sites in existing genes. Studying the Alu family in a human genomic context is likely to have general significance for our understanding of the evolutionary impact of other repetitive elements in diverse eukaryotic genomes.
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            Genetic polymorphisms in the renin-angiotensin system: relevance for susceptibility to cardiovascular disease.

            The renin-angiotensin system plays an important role in the pathogenesis of cardiovascular disease. Cloning of the human genes coding for the angiotensin-converting enzyme, angiotensinogen, and angiotensin II type 1 receptor has led to the discovery of several polymorphisms, which may be implicated in the pathogenesis of cardiovascular disease. The deletion/insertion (D/I) polymorphism of the angiotensin-converting enzyme gene is associated with hypertension in men, left ventricular hypertrophy in untreated hypertensive patients, various atherosclerotic cardiovascular complications, and microvascular disorders. The M235T polymorphism of the angiotensinogen gene may be associated with a higher risk of hypertension. The A1166C polymorphism of the angiotensin II type 1 receptor gene is probably correlated with hypertension and through an epistatic interaction with the D/I polymorphism of the angiotensin-converting enzyme gene possibly also with coronary heart disease. Several other gene polymorphisms, in particular those in the promoter area of the angiotensinogen gene, have been studied in relation to cardiovascular disease. Based on the insights gained from the reports summarized in this review article, population-based genetic studies of nuclear families are currently being conducted in Belgium and in the People's Republic of China with blood pressure and hypertension as the main outcome variables.
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              Association of angiotensinogen gene M235T and angiotensin-converting enzyme gene I/D polymorphisms with essential hypertension in Han Chinese population: a meta-analysis.

              The polymorphisms of angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) genes have been linked to increased risk of essential hypertension in multiple populations, but the results were inconsistent. To evaluate the associations of these polymorphisms with essential hypertension, we carried out a meta-analysis of the association studies within Han Chinese population. In this study, we reviewed two most commonly investigated polymorphisms, AGT M235T and ACE I/D, and provided summary estimates regarding their associations with essential hypertension. PubMed and China Biological Medicine Database were searched, and a total of 71 studies (31 studies for AGT M235T and 40 studies for ACE I/D) comprising 10 547 essential hypertension patients and 9217 controls from 23 provinces and special districts in China were finally included in this study. Statistically significant associations with essential hypertension were identified for TT genotype of AGT M235T polymorphism (odds ratio 1.54, 95% confidence interval 1.16-2.03, P = 0.002) and DD genotype of ACE I/D polymorphism (odds ratio 1.61, 95% confidence interval 1.32-1.98, P < 0.0001). Under dominant, recessive, and additive genetic models, positive associations were also found. The heterogeneity existed among the studies (P < 0.05), whereas the publication bias did not exist in both AGT analysis (P = 0.052) and ACE analysis (P = 0.103). The present meta-analysis suggests that AGT M235T and ACE I/D modulate the risk of essential hypertension in Han Chinese population.
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                Author and article information

                Journal
                Adv Biomed Res
                Adv Biomed Res
                ABR
                Advanced Biomedical Research
                Medknow Publications & Media Pvt Ltd (India )
                2277-9175
                2014
                28 May 2014
                : 3
                : 118
                Affiliations
                [1]Department of Genetics and Biotechnology, University of Calabar, Calabar, Cross River, Nigeria
                [1 ]Department of Zoology, University of Ibadan, Ibadan, Oyo, Nigeria
                [2 ]Virology Unit, International Institute of Tropical Agriculture, Ibadan, Oyo, Nigeria
                Author notes
                Address for correspondence: Dr. Mary Esien Kooffreh, Department of Genetics and Biotechnology, University of Calabar, PMB - 1115, Calabar, Cross River, Nigeria. E-mail: kooffreh2000@ 123456yahoo.co.uk
                Article
                ABR-3-118
                10.4103/2277-9175.133184
                4063107
                05c2ced7-56fb-46bc-8b21-8891252f7e42
                Copyright: © 2014 Kooffreh

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 June 2013
                : 04 December 2013
                Categories
                Original Article

                Molecular medicine
                angiotensin-converting enzyme gene,frequency,genotype,hypertension,i/d polymorphism

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