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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The evidence for the existence of genetic susceptibility variants for the common form of hypertension ("essential hypertension") remains weak and inconsistent. We sought genetic variants underlying blood pressure (BP) by conducting a genome-wide association study (GWAS) among African Americans, a population group in the United States that is disproportionately affected by hypertension and associated complications, including stroke and kidney diseases. Using a dense panel of over 800,000 SNPs in a discovery sample of 1,017 African Americans from the Washington, D.C., metropolitan region, we identified multiple SNPs reaching genome-wide significance for systolic BP in or near the genes: PMS1, SLC24A4, YWHA7, IPO7, and CACANA1H. Two of these genes, SLC24A4 (a sodium/potassium/calcium exchanger) and CACNA1H (a voltage-dependent calcium channel), are potential candidate genes for BP regulation and the latter is a drug target for a class of calcium channel blockers. No variant reached genome wide significance for association with diastolic BP (top scoring SNP rs1867226, p = 5.8 x 10(-7)) or with hypertension as a binary trait (top scoring SNP rs9791170, p = 5.1 x 10(-7)). We replicated some of the significant SNPs in a sample of West Africans. Pathway analysis revealed that genes harboring top-scoring variants cluster in pathways and networks of biologic relevance to hypertension and BP regulation. This is the first GWAS for hypertension and BP in an African American population. The findings suggests that, in addition to or in lieu of relying solely on replicated variants of moderate-to-large effect reaching genome-wide significance, pathway and network approaches may be useful in identifying and prioritizing candidate genes/loci for further experiments.
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PMID:A genome-wide association study of hypertension and blood pressure in African Americans. 1960 47

Intracerebral hemorrhage (ICH) can lead to tragic disability and mortality. Accumulating evidence has shown that sodium calcium exchanger (NCX) may contribute to the secondary injury of a stroke. Recently, a novel member of NCX, SLC24A6, was discovered with knowledge of its abundant distribution in brain. In the present study, we examined the time course of expression of SLC24A6 and its mediated intracellular calcium concentration ([Ca(2+)]i) to investigate its potential roles in brain damage after ICH. An ICH model was established as previously reported. Real-time PCR and Western blotting were used to test the mRNA and protein levels of SLC24A6 on the hemorrhagic side and on the contralateral side caudate nucleus tissues at 6 h, and on days 1, 3, 5, and 7 after ICH. Immunohistochemistry was used to analyze the morphological changes. Fura-2/AM loaded, dual wavelength spectrophotofluorometry was used to test [Ca(2+)]i. The data presented a remarkable decrease in SLC24A6 early after ICH, along with a comparable increase in [Ca(2+)]i. Our results indicated that SLC24A6 presents specific and remarkable alterations in both mRNA and protein levels after ICH. Decreases in SLC24A6 level were correlated with [Ca(2+)]i elevation. These data suggest that SLC24A6-mediated calcium overload plays an important role in brain damage after ICH.
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PMID:Alteration of intracellular calcium and its modulator SLC24A6 after experimental intracerebral hemorrhage. 2356 26

Dysregulation of calcium homeostasis has been linked to multiple neurological diseases. In addition to excitotoxic neuronal cell death observed following stroke, a growing number of studies implicate excess excitatory neuronal activity in chronic neurodegenerative diseases. Mitochondria function to rapidly sequester large influxes of cytosolic calcium through the activity of the mitochondrial calcium uniporter (MCU) complex, followed by more gradual release via calcium antiporters, such as NCLX. Increased cytosolic calcium levels almost invariably result in increased mitochondrial calcium uptake. While this response may augment mitochondrial respiration, limiting classic excitotoxic injury in the short term, recent studies employing live calcium imaging and molecular manipulation of calcium transporter activities suggest that mitochondrial calcium overload plays a key role in Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and related dementias [PD with dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD)]. Herein, we review the literature on increased excitatory input, mitochondrial calcium dysregulation, and the transcriptional or post-translational regulation of mitochondrial calcium transport proteins, with an emphasis on the PD-linked kinases LRRK2 and PINK1. The impact on pathological dendrite remodeling and neuroprotective effects of manipulating MCU, NCLX, and LETM1 are reviewed. We propose that shortening and simplification of the dendritic arbor observed in neurodegenerative diseases occur through a process of excitatory mitochondrial toxicity (EMT), which triggers mitophagy and perisynaptic mitochondrial depletion, mechanisms that are distinct from classic excitotoxicity.
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PMID:Excitatory Dendritic Mitochondrial Calcium Toxicity: Implications for Parkinson's and Other Neurodegenerative Diseases. 3011 73