Gene polymorphism of the renin-angiotensin system associates with risk for lacunar infarction: The Ohasama study

Abstract

The polymorphism of the angiotensin-converting enzyme gene is considered to be associated with increased risk for stroke, but there is a diversity in the results obtained. The genetic involvement of the renin-angiotensin system in stroke also remains unclear. To predict the genetic risk of lacunar infarction, we conducted an association study in an Ohasama population, which is the cohort in a rural region of northern Japan. A total of 134 subjects without major neurological, cardiovascular, or metabolic disorders were recruited. Using brain magnetic resonance imaging, the number of lacunae in each of four brain regions were calculated, and periventricular hyperintensity was classified into five grades. We used the following four candidate gene polymorphisms: angiotensin converting enzyme (ACE)/Insertion(I)-Deletion(D), angiotensinogen (AGT)/M235T, angiotensin II type 1 receptor (AT1)/ A1166C, type 2 receptor (AT2)/C3123A, to examine the association between polymorphisms and the severity of lacunar infarction. AGT/M235T was significantly associated with the number of lacunae in the brain stem, the basal ganglia (P < .05), and whole brain (P < .005) regions. The AT1 polymorphism was also significantly associated with the number of lacunae in the basal ganglia and whole brain regions (P < .05), and with periventricular hyperintensity grade (P < .005) in the younger population. However, ACE and AT2 polymorphisms failed to show an association with either the number of lacunae or the PVH grade. We concluded that AGT and AT1 polymorphisms are independent genetic risk factors for lacunar infarction.

Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients

“…9 We reported that subjects with the DD genotype have a higher risk of restenosis after emergency percutaneous coronary transluminal angioplasity, 10 hypertension in males 11 and stroke. 12 We also reported that subjects with the AGT TT genotype are at higher risk for lacunar infarction 13 and history of hypertension, 14 but not stroke. 12 Indeed, the literature contains many reports from other laboratories about these genotypes and cardiovascular disease, but many of these results remain controversial.…”

The CC genotype of the angiotensin II type I receptor gene independently associates with acute myocardial infarction in a Tunisian population

“…[13][14][15]18 Other studies reported the CC genotype to be associated with HTA, 19 coronary heart disease, 20 and stroke. 21 The A1166C polymorphism has been also studied in type 2 diabetic patients from India. 22 Interestingly, we found that diabetes and HTA were the most important risk factors for AMI in our population.…”

Salt Sensitivity of Japanese from the Viewpoint of Gene Polymorphism

“…2). Even though we did not directly examine the volume of sodium intake and excretion in the Ohasama Study, the positive association between AGT polymorphism and non-dipper (17) or lacunar infarction (12) suggests that angiotensinogen might be involved in the pathogenesis of salt-sensitive hypertension.…”

“…Our previous investigations revealed that several clinical features that are mainly related to hypertension are associated with genetic variants of the angiotensinogen gene (AGT) ( Table 1) (9-16). The T235 allele in exon 2 or C 31 allele in exon 1 of AGT has been associated with increased risk for hypertension (9), positive family history of hypertension (10), coronary heart disease (11) and lacunar infarction (12). To elucidate the detailed relation between blood pressure and AGT polymorphism, we recently assessed the genetic involvement of the T 31C polymorphism on circadian rhythm of blood pressure variation in the Ohasama Study (17).…”