Abstract

BackgroundThe angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D or indel) polymorphism has long been linked to Alzheimer’s disease (AD), but the interpretation of established data remains controversial. The aim of this study was to determine whether the angiotensin-converting enzyme is associated with the risk of Alzheimer’s disease in Tunisian patients.MethodsWe analyzed the genotype and allele frequency distribution of the ACE I/D gene polymorphism in 60 Tunisian AD patients and 120 healthy controls.ResultsThere is a significantly increased risk of AD in carriers of the D/D genotype (51.67% in patients vs. 31.67% in controls; p = .008, OR = 2.32). The D allele was also more frequently found in patients compared with controls (71.67% vs. 56.25%; p = .003, OR = 2.0). Moreover, as assessed by the Mini-Mental State Examination, patient D/D carriers were more frequently found to score in the severe category of dementia (65%) as compared to the moderate category (32%) or mild category (3%).ConclusionsThe D/D genotype and D allele of the ACE I/D polymorphism were associated with an increased risk in the development of AD in a Tunisian population. Furthermore, at the time of patient evaluation (average age 75 years), patients suffering with severe dementia were found predominantly in D/D carriers and, conversely, the D/D genotype and D allele were more frequently found in AD patients with severe dementia. These preliminary exploratory results should be confirmed in larger studies and further work is required to explore and interpret possible alternative findings in diverse populations.

Highlights

  • The angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D or indel) polymorphism has long been linked to Alzheimer’s disease (AD), but the interpretation of established data remains controversial

  • In either explanation of pathogenesis, the ACE I/D polymorphism becomes an important consideration as a risk factor for AD susceptibility

  • The analysis of genotype frequencies revealed an over-representation of the D/D genotype among patients compared to that of the control group (51.67% vs. 31.67%, respectively)

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Summary

Introduction

The angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D or indel) polymorphism has long been linked to Alzheimer’s disease (AD), but the interpretation of established data remains controversial. The most common polymorphism of the ACE gene is the insertion/deletion (I/D) variant of 287 base pairs in intron 16. This polymorphism has been suggested to be associated with serum ACE protein levels [5], the specific activity of the ACE protein domain [6], and the transcriptional activity of the ACE gene promoter region [7]. In either explanation of pathogenesis, the ACE I/D polymorphism becomes an important consideration as a risk factor for AD susceptibility Perhaps because of these diverse actions of ACE, potential associations with AD have been examined in a great number of studies worldwide but have generated equivocal results [9,10,11]

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