Angiotensin-converting enzyme insertion/deletion genotype (rs4646994) association with increased risk of stroke: a case-control study in Eastern Iran

血管紧张素转换酶插入/缺失基因型(rs4646994)与中风风险增加的关联:伊朗东部的一项病例对照研究

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Abstract

BACKGROUND AND OBJECTIVES: Ischemic stroke (IS), the predominant subtype of stroke, represents a complex and multifactorial disease. While a genetic predisposition is hypothesized to contribute to IS risk, the influence of specific gene variants remains unclear due to inconsistent findings across studies. This study aimed to evaluate the association between the angiotensin-converting enzyme insertion/deletion (ACE, I/D) gene polymorphism and the occurrence of IS in a patient cohort from Eastern Iran. METHODS: This case-control study was conducted at the Department of Neurology, Birjand University of Medical Sciences, Eastern Iran. The study population consisted of 406 participants, including 203 individuals diagnosed with IS and 203 age- and gender-matched healthy control subjects. The diagnosis of IS was established based on a comprehensive clinical evaluation, relevant laboratory analyses, neuroimaging, specifically computed tomographyو and magnetic resonance imaging. Genomic DNAs of participants were extracted from peripheral blood samples. The ACE I/D genotypes were determined using polymerase chain reaction amplification. RESULTS: The case group exhibited a higher prevalence of hypertension (71.4%), diabetes mellitus (33.5%), and dyslipidemia (36.9%), compared to the control group. Moreover, the mean systolic blood pressure was significantly elevated in the case group (146 mmHg) in comparison to the control group (123 mmHg). The ID and DD genotypes were more frequent in case subjects (46.6% and 36.8%, respectively) than in control subjects (40.2% and 32.6%, respectively). Conversely, the II genotype was more prevalent in control subjects (27.2%), compared to cases (16.6%). The D allele frequency was significantly higher in the case group (60.1%) than in the control group (52.7%) (p = 0.041, 95% CI: 0.554-0.988). DISCUSSION: This study demonstrated a higher prevalence of the ID and DD genotypes in individuals with IS, compared to control subjects. Furthermore, the D allele frequency was significantly elevated in the IS group.

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