angiotensinogen and Intracranial-Arteriosclerosis

The association of renin C-4063T and angiotensinogen (AGT) T174M, AGT M235T and AGT A-6G polymorphisms with ischemic stroke of atherosclerotic etiology was investigated in 329 Tunisian patients with stroke and 444 controls.. Genotyping was performed using PCR-RFLP and the contributions of polymorphisms to the risk of stroke were analyzed using haplotype and multivariate regression analysis.. AGT 235T and AGT-6G allele and AGT 235T/T, AGT-6A/G and AGT-6G/G genotype frequencies were higher in patients. Linkage disequilibrium (LD) was noted for AGT174T with AGT235M and AGT(-6)A in patients, while AGT235M was in LD with AGT(-6)A in controls and AGT235T was in LD with AGT(-6)G in both groups. The AGT 174T/235T/-6A and AGT 174T/235M/-6G haplotypes were positively and negatively associated with stroke respectively. Multivariate regression analysis identified AGT 174T/235M/-6A, AGT 174T/235T/-6G, AGT 174T/235T/-6A and AGT 174M/235T/-6A haplotypes to be significantly associated with an increased risk of stroke.. Renin-angiotensin-aldosterone system polymorphisms influence the risk of atherosclerotic stroke in Tunisians.

Topics: Angiotensinogen; Female; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Intracranial Arteriosclerosis; Linkage Disequilibrium; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Renin; Renin-Angiotensin System; Risk Factors; Stroke; Tunisia

While gene polymorphism for angiotensinogen (AGT) is reported to contribute to the regulation of blood pressure and salt sensitivity, its effect on the risk of ischemic stroke remains controversial. We hypothesized that polymorphism of the AGT gene could be a risk factor for ischemic stroke. Major clinical risk factors and the AGT gene M235T polymorphism were examined in 147 consecutive stroke patients and 133 healthy age-matched controls. All patients were categorized into four stroke types (single lacuna, multiple lacunae, large-artery atherosclerosis and branch atheromatous disease in brainstem) and two vascular groups (large and perforating arterial lesions). The AGT gene M allele significantly increased the risk of single lacuna, multiple lacunae and small arterial lesions, in male patients (p=0.029, 0.031 and 0.026, respectively). Synergistic effects of the AGT gene polymorphism and clinical risks were not observed. In conclusion, AGT M allele may present a risk of lacunar infarctions in Japanese men, independent of hypertension.

Topics: Aged; Aged, 80 and over; Angiotensinogen; Asian People; Brain; Brain Infarction; Brain Ischemia; Cerebral Arteries; DNA Mutational Analysis; Female; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Genetic Testing; Humans; Intracranial Arteriosclerosis; Japan; Male; Middle Aged; Polymorphism, Genetic; Risk Factors; Sex Characteristics; Sex Factors; Stroke