Search

Abstract: Stroke is a complex disease caused by combination of multiple risk factors. Recent findings have suggested that stroke has a significant genetic component. Various types of genetic polymorphisms have been suggested to contribute to the risk of stroke. Gene polymorphisms of renin-angiontensin aldosterone system (RAAS) have been suggested to be risk factors for hypertension, cardiovascular diseases and stroke. In the present case–control study we investigated the association of −344C/T (rs179998) polymorphism in the promoter region of the human aldosterone (CYP11B2) gene with genetic predisposition to hypertension, ischemic stroke and stroke subtypes classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Four hundred and three stroke patients (hypertensives:normotensives=219:184) and three hundred and ninety four, sex and age matched healthy controls (hypertensives:normotensives=118:276) were involved in the study. The region of interest in the CYP11B2 gene was amplified by polymerase chain reaction and genotypes determined by subjecting the PCR products to restriction digestion by the enzyme HaeIII. Significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. TT genotype and T allele associated significantly with hypertension and stroke (p <0.000 in hypertension and p =0.000 in case of stroke). A stepwise logistic regression analysis confirmed these findings. To establish that this polymorphism is associated with stroke independent of hypertension, we compared stroke patients without hypertension with normotensive controls. Significant difference was observed in genotypic distribution and allelic frequency between the two groups (p =0.000). Further evaluating the association of this polymorphism with stroke subtypes we found significant associations with intracranial large artery atherosclerosis, lacunar stroke and cardioembolic stroke (p =0.000 in each case). In conclusion our study suggests that −344T allele of CYP11B2 gene is an important risk factor for hypertension and ischemic stroke. However, this is a preliminary study and the results need to be confirmed in a larger cohort. [Copyright &y& Elsevier]

Abstract: Ischemic stroke is a leading cause of death throughout the world. An increasing number of studies have suggested that genetic factors are important in the stroke risk. The aim of our study was to investigate whether the Variable Number of Tandem Repeats (VNTR) polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene is associated with ischemic stroke in a South Indian population. 357 patients and 283 controls were enrolled in this case–control study. The ischemic stroke patients were classified according to TOAST classification. The eNOS gene polymorphism was determined by polymerase chain reaction–polyacrylamide gel electrophoresis. The genotypes were confirmed by sequencing the PCR products. There were significant differences in the genotype and allele frequencies of eNOS polymorphism between the patients with ischemic stroke and healthy controls (p =0.000). Multiple logistic regression analysis with forward stepwise selection using the potential confounders (sex, age, diabetes, hypertension, smoking and alcoholism) and eNOS gene variant revealed that the VNTR polymorphism in intron 4 of the eNOS gene is significantly [adjusted odds ratio=6.23, 95%CI (4.30–9.29), p =0.000] associated with ischemic stroke in the South Indian population from Andhra Pradesh. We did not find significant association of this polymorphism with any specific stroke subtype. Further hypertensives bearing 4a allele in high frequency are more predisposed to stroke. [Copyright &y& Elsevier]

Abstract: Stroke is the third largest cause of death and a major cause of adult disability and mortality worldwide. Experimental evidence suggests that genetic determinants do contribute a large part to stroke risk. The identification of phosphodiesterase 4D gene as a risk factor for stroke caused a great deal of interest in stroke genetics. Many of the studies of PDE4D gene have focused on the original Icelandic findings but the association between specific SNPs and haplotypes has been inconsistent. The aim of the present study was to investigate the association of three SNPs 32 (rs 456009), 83 (rs 966221) and 87 (rs 2910829), originally described by deCODE group; with stroke in a South Indian population from Andhra Pradesh. Two hundred and fifty ischemic stroke patients and two hundred and fifty controls were included in the study. The stroke patients were sub typed according to TOAST classification. SNP 83 showed significant association with stroke in the population under study while SNPs 87 and 32 were monomorphic. Further SNP 83 was found to be significantly associated with two stroke subtypes, intracranial large artery atherosclerosis (the most frequent subtype in the population) and small artery occlusion. The association with other subtypes was found to be insignificant. Further, SNP 83 was found to be associated significantly with some conventional stroke risk factors like diabetes and smoking. [Copyright &y& Elsevier]