Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Essential hypertension is a complex trait under polygenic control. Evidences suggests immune system involvement during pathogenesis. CC-chemokine receptor (CCR)5 and CCR2 are characterised by gene polymorphism. Variant alleles are derived from a deletion in the CCR5 gene (CCR5delta32) and a substitution mutation at the CCR2 locus (CCR264I). CCR polymorphic forms have been studied extensively as invasion cofactors for HIV-1, but they have also been implicated in immuno-related disorders. Here, we evaluate the allelic distribution of CCR5 and CCR2 genes in essential hypertension in a case-control study. Genotype frequency in a group of essential hypertensive patients (stage I-II; n=120) and a group of unrelated, healthy Caucasian subjects (n=340) is compared. CCR gene polymorphism is analysed by polymerase chain reaction and restriction enzyme digestion. A statistically significant difference was observed for CCR5 and CCR2 mutant alleles in essential hypertensive patients, compared with the controls (P=0.004 and P=0.003, respectively). CCR5delta32 and CCR264I alleles showed a 0.096 and 0.10 frequency among cases. To date, a role for the immune system in hypertension has not been clarified, nor has the predictive value of CCR polymorphisms.
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PMID:CCR5 and CCR2 gene polymorphisms in hypertensive patients. 1268 Jun 26

New genetic evidence strongly supports a role for the immune system in the pathogenesis of essential hypertension (EH) through chemokines and their receptors (CCR) involvement. The aim of the present study was to evaluate the possible relation between CCR2 and CCR5 alleles and blood pressure (BP) levels in hypertensive subjects. In all, 118 essential hypertensive outpatients (male 90, female 28; stage I and II; age 27-54 years; not previously treated with antihypertensive drugs) were selected for the study. All of the subjects underwent office BP measurement. Subsequently, 24-h ambulatory BP monitoring (ABPM) was performed with a Spacelabs 90207 monitor during a regular working day. CCR264I and CCR5Delta32 polymorphisms were determined by polymerase chain reaction (PCR), following the standard molecular biology protocols. Allelic frequencies were the following: CCR5Delta32= 0.097, CCR264I=0.101. Logistic regression analysis showed an association between the CCR5Delta32 allele and the following: 24-h systolic BP (SBP >140 mmHg; p = 0.027), values over the 50th percentile of 24-h SBP (p = 0.032), and the values over the 50th percentile of nighttime SBP (p = 0.039). Office BP showed an association with the Delta32 allele in a range over the 75th percentile of SBP (p = 0.087) and the 75th percentile of DBP (p = 0.085). No significant association was observed for CCR264I and BP levels or between physiological nocturnal BP decline and genotype. The observed results not only support the role of the immune system in the development and maintenance of hypertension, but they also indicate an influence of CCR5Delta32 polymorphism on the establishment of BP levels.
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PMID:Blood pressure regulation by CCR genes. 1706 59

Hypertension is the major risk factor for stroke, and genetic factors contribute to its development. Inflammation has been hypothesized to be the key link between blood pressure elevation and stroke. We performed an analysis of the association between inflammatory mediator gene polymorphisms and the incidence of stroke in patients with essential hypertension (EH). The study group consisted of 625 individuals (296 patients with noncomplicated EH, 71 hypertensive patients with ischemic stroke, and 258 control subjects). Both patients and controls were ethnic Tatars originating from the Republic of Bashkortostan (Russian Federation). The analysis has shown that the risk of ischemic stroke was associated with the CXCR2 rs1126579 polymorphism. Our results indicate that among patients with EH, the heterozygous genotype carriers had a higher risk of stroke (OR = 1.72, 95% CI 1.01-2.92), whereas the CXCR2*C/C genotype was protective against stroke (OR = 0.32, 95% CI 0.12-0.83). As shown by the gene-gene interaction analysis, the CXCR2 rs1126579 polymorphism was also present in all genotype/allele combinations associated with the risk of stroke. Genetic patterns associated with stroke also included polymorphisms in the CCL2, CCL18, CX3CR1, CCR5, and CXCL8 (IL8) genes, although no association between these loci and stroke was detected by individual analysis.
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PMID:The CXCR2 Gene Polymorphism Is Associated with Stroke in Patients with Essential Hypertension. 2664 69

Cell migration towards a chemotactic stimulus relies on the re-arrangement of the cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4, breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and Jurkat T-cells. For CCL3-induced migration via CCR1 and/or CCR5, Rac1 signalling does not regulate cell migration in either suspension or adherent cells. We have confirmed the involvement of Rac1 with the use of a specific Rac1 blocking peptide. We also used a Rac1 inhibitor EHT 1864 and a Rac1-GEF inhibitor NSC23766 to probe the importance of Rac1 in chemotaxis. Both inhibitors did not block CCL3-induced chemotaxis, but they were able to block CXCL12-induced chemotaxis. This confirms that Rac1 activation is not essential for CCL3-induced migration, however NSC23766 might have secondary effects on CXCR4. This small molecule exhibits agonistic features in internalisation and cAMP assays, whereas it acts as an antagonist for CXCR4 in migration and calcium release assays. Our findings strongly suggest that Rac1 activation is not necessary for CCL3 signalling, and reveal that NSC23766 could be a novel CXCR4 receptor ligand.
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PMID:Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4. 2905 Sep 86