Jornal Vascular Brasileiro
https://jvascbras.org/article/doi/10.1590/1677-5449.202501422
Jornal Vascular Brasileiro
Artigo Original

Case-control study on the association of angiotensin-converting enzyme gene I/D rs4646944 single nucleotide polymorphism and young-onset cryptogenic ischemic stroke in an Algerian cohort

Estudo de caso-controle sobre associação do polimorfismo de nucleotídeo único I/D rs4646944 do gene da enzima conversora de angiotensina e acidente vascular isquêmico criptogênico de início precoce em coorte argelina

Mohamed Lebsir; Mohamed Larbi Rezgoun; Boubekeur Saddik Fekraoui; Brahim Djoudi; Yasmina Boukhenaf; Amina Ines Bernou; Karima Sifi

http://dx.doi.org/10.1590/1677-5449.202501422 J Vasc Bras, vol.25, e20250142, 2026
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Abstract

Background: Numerous studies have shown a link between the angiotensin-converting enzyme (ACE) and ischemic stroke. Cryptogenic ischemic stroke is the most commonly recorded form of ischemic stroke among young adults. The insertion/deletion (I/D) variant of ACE (rs4646994) has been linked to ischemic stroke.

Objectives: We examined the potential correlation between this single nucleotide polymorphism and cryptogenic ischemic stroke in young adults.

Methods: This case-control study included 42 young adults (< 50 years of age) diagnosed with cryptogenic ischemic stroke according to the TOAST classification, along with 42 healthy controls from the general population. The vascular risk factors included hypertension, diabetes mellitus, dyslipidemia, smoking, and cardiovascular diseases. Genomic deoxyribonucleic acid was extracted, and the ACE rs4646994 polymorphism was examined using polymerase chain reaction.

Results: Younger age (p = 0.004) and female sex (p = 0.007) were significantly connected to an increased risk of stroke, contrasting with typical stroke demographics. Hypertension (p = 0.002) and smoking (p = 0.04) emerged as important, modifiable risk factors. There was no notable distinction between patients and controls regarding the frequencies of alleles and genotypes of the ACE I/D single nucleotide polymorphism (p > 0.05). These results were not associated with cryptogenic ischemic stroke.

Conclusions: While aligning with the current literature, our results are constrained by the limited sample size, the case-control design, and the dependence on self-reported data, which could have led to bias. This genetic study of a population from eastern Algeria did not show a link between the ACEI/D single nucleotide polymorphism and cryptogenic ischemic stroke.

Keywords

angiotensin-converting enzyme polymorphism; cryptogenic ischemic stroke; young onset

Resumo

Contexto: Vários estudos demonstraram associação entre enzima conversora de angiotensina (ECA) e acidente vascular cerebral (AVC) isquêmico. AVC isquêmico criptogênico é a forma mais frequentemente registrada de AVC isquêmico entre adultos jovens. A variante de inserção/deleção (I/D) da ECA (rs4646994) tem sido associada ao AVC isquêmico.

Objetivos: Investigamos possível correlação entre esse polimorfismo de nucleotídeo único e AVC isquêmico criptogênico em adultos jovens.

Métodos: Caso-controle incluiu 42 adultos jovens (< 50 anos) diagnosticados com AVC isquêmico criptogênico segundo a classificação TOAST, juntamente com 42 controles saudáveis da população geral. Fatores de risco vascular incluíram hipertensão, diabetes melito, dislipidemia, tabagismo e doenças cardiovasculares. Ácido desoxirribonucleico genômico foi extraído, e polimorfismo rs4646994 foi analisado por meio da reação em cadeia da polimerase.

Resultados: Idade mais jovem (p = 0,004) e sexo feminino (p = 0,007) foram significativamente associados a risco aumentado de AVC, contrastando com perfil demográfico típico dessa condição. Hipertensão (p = 0,002) e tabagismo (p = 0,04) mostraram-se fatores de risco importantes e modificáveis. Não houve diferença significativa entre pacientes e controles quanto às frequências de alelos e genótipos do polimorfismo de I/D da ECA (p > 0,05). Esses resultados não demonstraram associação com AVC isquêmico criptogênico.

Conclusão: Embora estejam alinhados com a literatura atual, os resultados apresentam limitações decorrentes do tamanho reduzido da amostra, do delineamento do estudo e da dependência de dados autorreferidos, fatores que podem ter introduzido viés. Este estudo, realizado em uma população do leste da Argélia, não demonstrou associação entre polimorfismo de I/D da ECA e AVC isquêmico criptogênico.

Palavras-chave

polimorfismo ECA; acidente vascular cerebral isquêmico criptogênico; início precoce

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Submetido em:
19/03/2026

Aceito em:
22/07/2026

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