Publications by authors named "Shruthi Shimoga Ramesh"

2 Publications

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

Pharmacogenomics J 2020 10 4;20(5):655-663. Epub 2020 Feb 4.

Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bengaluru, 560029, India.

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.
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October 2020

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

J Neurosci Rural Pract 2014 Nov;5(Suppl 1):S22-7

Department of Biostatistics, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.

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.
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November 2014