Patients with Invasive Tumors and eNOS Gene Polymorphisms with Subarachnoid Hemorrhage Tend to Have Poorer Prognosis.

Context Endothelial nitric oxide synthase ( eNOS) gene polymorphisms are found to predict predisposition to aneurysmal rupture and development of vasospasm in a patient of subarachnoid hemorrhage (SAH). eNOS gene polymorphisms are also found to predict invasiveness of malignant cells. Studies are not available in literature to describe the effect of eNOS gene polymorphisms and correlation between aneurysm and carcinoma. This study aims to investigate whether positive cancer history influences clinical outcome following SAH and eNOS gene polymorphisms. Materials and Methods The eNOS gene polymorphisms were analyzed in seven consecutive patients (mean age, 52.28 ± 20 years) with a diagnosis of invasive systemic tumors from 2011 to 2017. The eNOS 4a/4b eNOS -786T> eNOS 894G > T polymorphisms of the eNOS gene were determined by polymerase chain reaction and restriction fragment length polymorphism. Results Seven patients of aneurysmal SAH in association with malignancies were studied for eNOS polymorphisms expression and outcome. Three patients had carcinoma cervix: one patient of carcinoma breast and one each of transitional cell carcinoma of urinary bladder, spindle cell carcinoma of left kidney, and untreated patient of atypical pituitary (adenoma). A genotype study of eNOS gene polymorphisms in these patients shows common polymorphisms are involved in the determination of disease progression in malignancies and aneurysmal SAH. Conclusion Patients who expressed 4ab, eNOS -786T > TT/CC/TC, eNOS 894G > T GG/GT polymorphisms did better than patients who expressed only 4bb, though both were associated with poor prognosis.

Estrogen receptor alpha gene variant, PvuII (rs2234693), as a potential pharmacogenetic biomarker for aneurysmal subarachnoid hemorrhage in postmenopausal women.

Aneurysmal subarachnoid hemorrhage (aSAH) occurs more often in postmenopausal women than in men. Estrogen plays an important role in vascular homeostasis. Our aim was to elucidate whether a drop in circulating estradiol in conjunction with variants of estrogen receptor genes have a role in female gender susceptibility to aSAH. A total of 709 subjects were enrolled (349 aSAH patients, 360 controls) and genotyped for rs2234693 or PvuII (intron 1, T>C) in the ESR1 gene and rs4986938 or AluI (exon 8, 1730G>A) of ESR2 gene by PCR-RFLP. Serum estradiol was estimated by ELISA. Estrogen receptor gene expression was studied by qRT-PCR. Logistic regression analysis indicated a significant recessive effect of the T allele of PvuII on aSAH in females, and this association remained statistically significant even after adjusting for confounders (OR 1.702, CI 95% 1.062, 2.726, P value = 0.027). ESR1 gene expression was significantly reduced (P value = 0.0089) in subjects carrying PvuII T allele. In postmenopausal women with TT genotype and low serum estradiol, the odds for developing aSAH were found to be 3.5-fold increase compared with premenopausal women (CI 95% 1.424-8.828, P value = 0.0074). However, this variant showed no significant association with aSAH in men. No significant difference was found in genotype and allelic distribution of AluI polymorphism in ESR2 gene, between patients and controls. We propose that the PvuII T allele could be a potential pharmacogenetic marker for strategizing personal medicine for preventing aSAH in postmenopausal women with low circulating estradiol. Further larger studies in other population are warranted.

Correlation between plasma total nitric oxide levels and cerebral vasospasm and clinical outcome in patients with aneurysmal subarachnoid hemorrhage in Indian population.

CONTEXT: Cerebral vasospasm remains a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Reduced bioavailability of nitric oxide has been associated with the development of cerebral vasospasm after aSAH. Such data is not available in Indian population. AIMS: The objective of the study was to measure the plasma total nitric oxide (nitrite and nitrate-NO x ) level in aSAH patients and healthy controls treated at a tertiary hospital in India and to investigate a possible association between plasma total nitric oxide level and cerebral vasospasm and clinical outcome following treatment in patients with aSAH. SETTINGS AND DESIGN: A case-control study of aSAH patients was conducted. Plasma total NO x levels were estimated in aSAH patients with and without vasospasm and compared the results with NO x levels in healthy individuals. MATERIALS AND METHODS: aSAH in patients was diagnosed on the basis of clinical and neuro-imaging findings. Plasma total NO x levels in different subject groups were determined by Griess assay. RESULTS: Plasma total NO x level was found to be significantly decreased in patients with aSAH when compared to controls. Plasma total NO x level in the poor-grade SAH group was lower than that in the good-grade SAH group. Plasma total NO x level further reduced in patients with angiographic (P < 0.05) and clinical vasospasm. CONCLUSIONS: Reduced plasma NO x level is seen in aSAH patients as compared to normal individuals. In aSAH patients reduced levels are associated with increased incidence of cerebral vasospasm and poor outcome. Plasma total NO x level could be used as a candidate biomarker for predicting vasospasm and outcome for this pathology.