Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

US and British studies have shown significantly higher incidence of strokes due to thromboembolism, subarachnoid hemorrhage, and cerebral venous thrombosis in users of oral contraceptives, particularly high estrogen formulations. Estrogen increases plasma levels of fibrinogen and the clotting factors VII, VIII, IX, X, and XII; enhances platelet aggregation; and suppresses antithrombin III and the fibrinolytic system. Estrogen may also cause immune-mediated vasculitis. The risk of strokes increases for women over 35 and smokers. Estrogen-induced chorea, including chorea of pregnancy, may be due to direct dopaminergic action of estrogens or to an accumulation of dopamine in the brain caused by competitive binding to the dopamine-degrading enzyme catechol-o-methyltransferase. Epileptics taking anticonvulsants and oral contraceptives have 25 times the risk of pill failure as normally expected, due to metabolism of anticonvulsants, such as phenytoin, phenobarbital, primidone, carbamazepine, and ethosuximide, by the hepatic microsomal enzyme system, resulting in a dramatic decrease of circulating ethinyl estradiol. Available options are to increase the estrogen dose to as much as 100 mg, to substitute valproic acid for other anticonvulsants, or to augment ethinyl estradiol levels by oral administration of ascorbic acid, which increases the bioavailability of the steroid. During pregnancy, on the other hand, serum levels of anticonvulsants decrease by 30-40%.
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PMID:Sex hormones in stroke, chorea, and anticonvulsant therapy. 305 49

Antineutrophil cytoplasmic autoantibody (ANCA) causes vascular injury that leads to small-vessel vasculitis. Patients with ANCA aberrantly express neutrophil granule-encoding genes, including 2 that encode autoantigens: proteinase 3 (PR3) and myeloperoxidase (MPO). To uncover a potential transcriptional regulatory mechanism for PR3 and MPO disrupted in patients with ANCA vasculitis, we examined the PR3 and MPO loci in neutrophils from ANCA patients and healthy control individuals for epigenetic modifications associated with gene silencing. We found that levels of the chromatin modification H3K27me3, which is associated with gene silencing, were depleted at PR3 and MPO loci in ANCA patients compared with healthy controls. Interestingly, in both patients and controls, DNA was unmethylated at a CpG island in PR3, whereas in healthy controls, DNA was methylated at a CpG island in MPO. Consistent with decreased levels of H3K27me3, JMJD3, the demethylase specific for H3K27me3, was preferentially expressed in ANCA patients versus healthy controls. In addition, we describe a mechanism for recruiting the H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) to PR3 and MPO loci mediated by RUNX3. RUNX3 message was decreased in patients compared with healthy controls, and may also be under epigenetic control. DNA methylation was increased at the RUNX3 promoter in ANCA patients. These data indicate that epigenetic modifications associated with gene silencing are perturbed at ANCA autoantigen-encoding genes, potentially contributing to inappropriate expression of PR3 and MPO in ANCA patients.
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PMID:Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis. 2106 38