Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic association analysis has suggested that IMPA2 is a susceptibility gene for ischemic stroke (IS). To explore the association between IMPA2 polymorphisms and the risk of IS in a Han Chinese population, candidate gene association was performed using data from a case-control study of 488 IS patients and 503 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association, and associations were evaluated under dominant, recessive, and additive genetic models using PLINK software. There was a statistically significant difference in the "TC" genotype frequency of the IMPA2 polymorphism rs589247, between cases and controls (50.0% vs. 45.3%). Under the dominant model, rs589247 was associated with an increased risk of IS (OR=1.32, 95%CI: 1.01-1.73; P=0.040). There were no other associations between any of the seven additional IMPA2 polymorphisms and IS risk. This study is the first to find a correlation between an IMPA2 polymorphism and IS risk in a northwest Han Chinese population. These results may help to elucidate the molecular pathogenesis of this disease, and could potentially be used to predict IS risk. However, further studies are still needed to validate this association in other populations and with larger sample sizes.
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PMID:IMPA2 polymorphisms and risk of ischemic stroke in a northwest Han Chinese population. 2766 Nov 9

Genome-wide association studies have identified putative ischemic stroke risk genes, yet, their expression after stroke is unexplored in spite of growing interest in elucidating their specific role and identifying candidate genes for stroke treatment. Thus, we took an exploratory approach to investigate sexual dimorphism, alternative splicing, and etiology in putative risk gene expression in blood following cardioembolic, atherosclerotic large vessel disease and small vessel disease/lacunar causes of ischemic stroke in each sex compared to controls. Whole transcriptome arrays assessed 71 putative stroke/vascular risk factor genes for blood RNA expression at gene-, exon-, and alternative splicing-levels. Male (n = 122) and female (n = 123) stroke and control volunteers from three university medical centers were matched for race, age, vascular risk factors, and blood draw time since stroke onset. Exclusion criteria included: previous stroke, drug abuse, subarachnoid or intracerebral hemorrhage, hemorrhagic transformation, infection, dialysis, cancer, hematological abnormalities, thrombolytics, anticoagulants or immunosuppressants. Significant differential gene expression (fold change > |1.2|, p < 0.05, partial correlation > |0.4|) and alternative splicing (false discovery rate p < 0.3) were assessed. At gene level, few were differentially expressed: ALDH2, ALOX5AP, F13A1, and IMPA2 (males, all stroke); ITGB3 (females, cardioembolic); ADD1 (males, atherosclerotic); F13A1, IMPA2 (males, lacunar); and WNK1 (females, lacunar). GP1BA and ITGA2B were alternatively spliced in both sexes (all patients vs. controls). Six genes in males, five in females, were alternatively spliced in all stroke compared to controls. Alternative splicing and exon-level analyses associated many genes with specific etiology in either sex. Of 71 genes, 70 had differential exon-level expression in stroke patients compared to control subjects. Among stroke patients, 24 genes represented by differentially expressed exons were male-specific, six were common between sexes, and two were female-specific. In lacunar stroke, expression of 19 differentially expressed exons representing six genes (ADD1, NINJ2, PCSK9, PEMT, SMARCA4, WNK1) decreased in males and increased in females. Results demonstrate alternative splicing and sexually dimorphic expression of most putative risk genes in stroke patients' blood. Since expression was also often cause-specific, sex, and etiology are factors to consider in stroke treatment trials and genetic association studies as society trends toward more personalized medicine.
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PMID:Alternative Splicing of Putative Stroke/Vascular Risk Factor Genes Expressed in Blood Following Ischemic Stroke Is Sexually Dimorphic and Cause-Specific. 3319 47