angiotensinogen and Brain-Infarction

The angiotensinogen (AGT) gene M235T polymorphism has been reported to be associated with myocardial infarction (MI) and brain infarction (BI), but the results remain inconclusive. This meta-analysis was designed to clarify these controversies. Electronic databases were systematically searched before February 2013. A total of 38 studies with 17304 subjects met our inclusion criteria. In East Asian group, significant association was found between AGT M235T polymorphism and risk of MI (for dominant model: OR=1.79; 95% CI=1.04-3.06; for recessive model OR=2.01; 95% CI=1.21-3.36; for additive model OR=1.79; 95% CI=1.14-2.86) as well as BI (for dominant model: OR=1.66; 95% CI=1.22-2.27; for recessive model OR=1.78, 95% CI=1.29-2.46; for additive model: OR=1.64, 95% CI=1.34-2.00), while the M235T polymorphism did not impact the risk of MI in total population and other ethnicity. In the subgroup analyses by gender and age, there was lack of evidence for the association. This meta-analysis suggested an association between the M235T polymorphism and MI as well as BI in East Asian population. Further studies with larger numbers of worldwide participants are needed to understand the genetic basis of MI and BI.

Topics: Angiotensinogen; Asia, Eastern; Asian People; Brain Infarction; Humans; Myocardial Infarction; Polymorphism, Genetic; Risk Factors; White People

Genetic variation in the renin-angiotensin system (RAS) has been implicated in stroke, particularly the small vessel disease (SVD) subtype. Furthermore, there may be two distinct subtypes of cerebral SVD, isolated lacunar infarction (ILI) and ischaemic leukoaraiosis (ILA).. 300 patients with well-phenotyped SVD and 600 controls were genotyped for five polymorphisms in the angiotensinogen (AGT) gene and eight polymorphisms within the angiotensin-converting enzyme (ACE) gene.. AGT and ACE polymorphisms and haplotypes were no more common in SVD cases as a whole or the two subtypes. Amongst hypertensives only, an AGT promoter polymorphism (-20A-->C), was associated with the ILA subtype (multivariate odds ratio 1.716, 95% confidence interval 1.073-2.746, p = 0.024).. RAS genetic variants are not strong risk factors for cerebral SVD. The AGT -20C allele may be a risk factor for the leukoaraiosis subtype amongst hypertensives.

Topics: Angiotensinogen; Blood Vessels; Brain; Brain Infarction; Brain Ischemia; Case-Control Studies; Cerebrovascular Disorders; Gene Frequency; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Hypertension; Leukoaraiosis; Linkage Disequilibrium; Logistic Models; Odds Ratio; Peptidyl-Dipeptidase A; Phenotype; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Renin-Angiotensin System; Risk Assessment; Risk Factors; United Kingdom

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

The renin-angiotensin-aldosterone system has functions that may contribute to brain infarction (BI). In 459 matched pairs of white patients and control subjects, we measured plasma angiotensin-converting enzyme (ACE) levels, seven polymorphisms (angiotensinogen T174M and M235T, ACE I/D and 4656 2/3CT repeat [rpt], angiotensin II type 1 receptor A1166C and A153G, and aldosterone synthase CYP11B2), and evaluated 5-year poststroke mortality. Mean plasma ACE levels (+/-standard error) were significantly greater in patients than control subjects (37.5 +/- 0.9 vs 33.9 +/- 0.9), in patients with lacunar stroke, and in patients with no previous vascular (cerebrovascular or cardiovascular) history. The risk for BI increased with tertiles of plasma ACE, without an interaction with hypertension. After adjustments, the association disappeared except among patients with cardioembolic BI and those without previous vascular events. Among the polymorphisms, there was a weak association of BI with angiotensin II type 1 receptor 1166C, a weak protective effect with angiotensinogen 174M, and a strong association of angiotensinogen 235T with 5-year vascular mortality. These results suggest that renin-angiotensin-aldosterone system activity and genes contribute to cerebrovascular disease and poststroke vascular death in white patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensinogen; Brain Infarction; Case-Control Studies; Cytochrome P-450 CYP11B2; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Renin-Angiotensin System