Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Contributes to Ischemic Stroke Risk: A Meta-Analysis of 50 Case-Control Studies

Abstract

BackgroundMany studies have investigated the association between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk of ischemic stroke. However, the evidence is inadequate to draw robust conclusions because most studies were generally small and conducted in heterogeneous populations. To shed light on these inconclusive findings, we conducted a large meta-analysis of studies relating the ACE I/D polymorphism to the risk of ischemic stroke.MethodsRelevant studies were identified by searching PubMed and Embase through February 2012 and by reviewing the references of retrieved articles. We included studies that reported odds ratio (OR) with 95% confidence interval (CI) for the association between this polymorphism and ischemic stroke risk.ResultsFifty independent publications, with 10 070 stroke cases and 22 103 controls, were included. The results indicated that the DD homozygote carriers had a 37% higher risk of ischemic stroke when compared with the homozygotes II and heterozygote ID [odds ratio (OR) = 1.37, 95% confidence interval (CI): 1.22–1.53]. Subgroup analyses indicated that this higher risk was more pronounced among Asians, hospital-based studies, and small vessel disease (SVD). Potential publication bias may exist, but correction for this bias using a formal statistical method did not materially alter the combined risk estimate.ConclusionThe results of our meta-analysis indicate that the D allele of ACE I/D polymorphism is a low-penetrance susceptibility marker of ischemic stroke.

Lack of association between potential prothrombotic genetic risk factors and arterial and venous thrombosis

“…The deletion of a 287-bp sequence in intron 16 of the ACE gene is associated with increased levels of transcription of messenger RNA, and hence with increased ACE expression. Thus, in carriers of the DD genotype, ACE levels are higher than in those with genotype ID or II (Zhang et al, 2012). Prandoni's study (2007) of patients with venous thrombosis showed a moderate increase in risk for male patients with the DD genotype, but no increase in risk for women patients with the same genotype.…”

“…Zhang et al (2012) also reported that the deletion polymorphism in the ACE gene is an important risk factor for venous thrombosis after orthopedic surgery; the homozygous DD genotype increased thrombotic risk by more than 11 times, and the heterozygous ID genotype increased the risk by about five times.…”

“…The deletion of a 287-bp sequence in intron 16 of the ACE gene is associated with increased levels of transcription of messenger RNA and hence with increased ACE expression (Jackson et al, 2000;Fatini et al, 2009). Thus, carriers of the DD genotype are associated with higher plasma levels of the enzyme than those with the ID (intermediate levels) or II (low levels) genotypes (Jackson et al, 2000;Zhang et al, 2012).…”

The ACE Gene Insertion/Deletion Polymorphism and Cerebrovascular Diseases in Uzbek Patients with Arterial Hypertension

“…[16] A recent meta-analysis revealed the D allele as a low-penetrance susceptibility marker for IS. [17] It is possible that ACE gene I/D polymorphism can modulate cerebrovascular risk only in combination with other risk factors, such as HE, hyperlipidemia, smoking, diabetes, and systemic atherosclerosis. In our study, we found a significant association between the ID allele and pronounced disorders in BP profile, high levels of TC, TG, VLDL-C, and IMT values.…”

Ischemic stroke in a young man with MTHFR A1298C and ACE I/D polymorphism

“…ACE gene is located on chromosome 17q23, where an insertion/deletion polymorphism in intron 16 has been identified. This polymorphism is based on the presence (insertion, I) or absence (deletion, D) of a 287-bp DNA fragment (9).…”