Abstract
The endothelial nitric oxide synthase (eNOS) encoded by the NOS3 gene is responsible for the synthesis of a vasoactive endothelium-derived nitric oxide (NO). The genetic polymorphism of this gene explains, in part, why some people are prone to develop stroke than others. In this study we conducted a case control study in Bahrainis to investigate “for the first time” the relationship between NOS3 894G > T (rs1799983) and 786T > C (rs2070744) polymorphisms with the stroke predisposition in Bahraini population. Detection of NOS3 polymorphism was performed by PCR RFLP genotyping method. The level of NO among cases and controls was measured using ELISA. A total of 93 unrelated stroke patients and 86 controls were included in the study. The three types of stroke; Ischemic, hemorrhagic and transient ischemic attack were reported (91.4%, 7.5% and 1.1% respectively). No significant gender difference was observed (P = 0.74). Having previous stroke was a highly significant risk factor of the disease (P = 0.001, OR = 1.4), where as a family history of stroke was not (OR = 0.11). The analysis provides evidence that the mutant 894GT + TT genotypes of NOS3 894G > T polymorphism were positively associated with stroke predisposition and it increased the risk of stroke nearly two folds (P = 0.037, OR = 1.936). Although we found an association between the mutant genotype786 TC + CC of the NOS3 786T > C polymorphism with the susceptibility to stroke (P = 0.023) suggesting that the mutant C allele might have a protective effect against stroke in this population, the strength of this association was rather low (OR = 0.484). The level of NO in stroke patients was significantly low compared to healthy controls (P 0.005). Diabetes, hypertension, heart diseases were reported in stroke patients (67%, 71.4% and 52.1% respectively). More over 50% of the cases with previous stroke are both diabetic and hypertensive. This indicates that these diseases could be considered as a significant factor in the development of stroke in this population. We concluded that the NOS3-894 G > T polymorphism is a potential risk factor of stroke in Bahraini population, whereas as the NOS3 786T > C polymorphism might have a possible protective role against the disease in this population.
Highlights
A stroke results when the blood supply to the brain is suddenly cut off or interrupted
The analysis provides evidence that the mutant 894GT + TT genotypes of Nitric oxide synthase3 gene (NOS3) 894G > T polymorphism were positively associated with stroke predisposition and it increased the risk of stroke nearly two folds (P = 0.037, odds ratio (OR) = 1.936)
Our result revealed a significant association of the mutant 894GT + TT genotypes of the NOS3 894G > T polymorphism with stroke predisposition (χ2 = 4.36, P = 0.037) which is consistent with the finding of the previous studies [27] and those conducted in Korean and other Asian population [19] [20]
Summary
A stroke results when the blood supply to the brain is suddenly cut off or interrupted. This can occur when a blood vessel in the brain or neck is blocked or bursts, leading to brain cells’ death. Stroke is a fourth leading cause of death in the developed world [1] and it is a major cause of adult disability. All are risk factors of stroke [1] [2] [3] [4]. Over a third of stroke deaths occur in developing countries [3]. Arab countries constitute populations with a lifestyle and diet that may influence stroke risk. The incidence of stroke in Bahrainis is rising over the last 16 years (110/100,000) [5] compared to the incidence of 57/100,000 reported in 1995 [6]
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