Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21817 (RyR1)
 1,154 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High blood pressure is a predictor of cardiovascular disease. Hence, genes contributing to essential hypertension may play a role in the etiology of cardiovascular disease. For this reason, we examined the association between the alpha-adducin (ADD1) G460W and G-protein beta3 subunit (GNB3) 825C>T polymorphisms and the prevalence of peripheral arterial disease (PAD) and incidence of coronary heart disease (CHD) in non-Hispanic whites from the Atherosclerosis Risk in Communities (ARIC) Study. PAD prevalence was defined by an ankle-brachial index, ie, the ratio of ankle systolic blood pressure to brachial artery systolic blood pressure, of </=0.90 for men and </=0.85 for women. CHD incidence was determined by following the ARIC cohort for a median of 5.3 years for potential coronary events. Stratified random samples of the ARIC cohort (n=703 and n=684) were used, respectively, as the comparison groups for the PAD (n=144) and incident CHD (n=408) cases. The GNB3 825T allele and the ADD1 460W allele were not significantly associated with prevalence of PAD or incidence of CHD. However, a test of the interaction between hypertension status and the ADD1 G460W polymorphism indicated that further evaluation of the ADD1 polymorphism in only hypertensive individuals was warranted. The ADD1 460W allele was significantly associated with PAD (odds ratio [OR]: 2.61, 95% CI, 1.27-5.37, P=0.01) and CHD (hazard rate ratio [HRR]: 2.30, 95% CI, 1.20-4.42, P=0.01) in hypertensive individuals after adjustment for multiple cardiovascular disease risk factors. An interaction with hypertension in the association between the ADD1 G460W polymorphism and cardiovascular disease merits further testing in additional populations.
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PMID:ADD1 460W allele associated with cardiovascular disease in hypertensive individuals. 1205 41

Interleukin-6 (IL-6) and C-reactive protein (CRP) levels increase with age and likely play a role in adverse health outcomes in older adults. The relationship between IL-6 gene tag single nucleotide polymorphisms (SNPs) and circulating IL-6 and CRP levels, cardiovascular disease (CVD) outcomes, and mortality in Caucasian (CA) and African American (AA) participants of the Cardiovascular Health Study (CHS) was evaluated using ANCOVA and Cox proportional hazards models. The minor allele of the promoter SNP 1510 and intronic SNP 3572 associates with significantly higher serum IL-6 and CRP levels in CA but not AA. The CRP association persisted after CA and AA populations were combined and after accounting for multiple comparisons. These associations did not carry through to cardiovascular disease outcomes. Decreased risk of stroke was identified in CA, with the minor allele of SNP 1111 (HRR 0.71, 95% CI 0.52, 0.95), P = 0.02, and increased risk of CVD and all-cause mortality (HRR 1.31, 95% CI 1.05-1.64) in AAs heterozygote for SNP 2989. While genetic variation in the IL-6 gene was associated with circulating IL-6 and especially with CRP concentrations in this study, there is little evidence for association between common IL-6 gene variation and adverse health outcomes in this population of older adults.
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PMID:IL-6 gene variation is associated with IL-6 and C-reactive protein levels but not cardiovascular outcomes in the Cardiovascular Health Study. 1785 95

Although studies have shown an inverse association between cardiorespiratory fitness (CRF) and C-reactive protein (CRP) levels, the underlying mechanisms are not fully understood. There is emerging evidence that autonomic nervous system function is related to CRP levels. Because high CRF is related to improved autonomic function, we hypothesized that the association between high CRF and low CRP levels would be affected by autonomic nervous system function. Cross-sectional analyses were conducted on 2,456 asymptomatic men who participated in a medical screening program. Fasting blood samples for cardiovascular disease risk factors were analyzed, and CRF was measured by maximal exercise treadmill test with expired gas analysis. We used an index of cardiac autonomic imbalance defined as the ratio of resting heart rate to 1 min of heart rate recovery after exercise (RHR/HRR). CRF was significantly correlated with CRP (r = -0.16, P < 0.05), and RHR/HRR (r = -0.48, P < 0.05), while RHR/HRR was significantly correlated with CRP (r = 0.25, P < 0.05). In multivariable linear regression models that adjusted for age, body mass index, smoking, disease status, medications, lipid profiles, glucose, and systolic blood pressure, CRF was inversely associated with CRP (beta = -0.09, P < 0.05). However, this relationship was no longer significant after adjusting for RHR/HRR in a multivariable linear regression model (beta = -0.03, P = 0.29). These results suggest that autonomic nervous system function significantly affects the relationship between CRF and inflammation in middle-aged men. Thus, physical activity or exercise training may favorably affect the cholinergic antiinflammatory pathway, but additional research is needed to confirm this finding.
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PMID:The inverse association between cardiorespiratory fitness and C-reactive protein is mediated by autonomic function: a possible role of the cholinergic antiinflammatory pathway. 1960 5

Background Hypertension is the major risk factor for cardiovascular disease, the most common cause of death worldwide. Resistance arteries are capable of adapting their diameter independently in response to pressure and flow-associated shear stress. Ryanodine receptors (RyRs) are major Ca2+-release channels in the sarcoplasmic reticulum membrane of myocytes that contribute to the regulation of contractility. Vascular smooth muscle cells exhibit 3 different RyR isoforms (RyR1, RyR2, and RyR3), but the impact of individual RyR isoforms on adaptive vascular responses is largely unknown. Herein, we generated tamoxifen-inducible smooth muscle cell-specific RyR2-deficient mice and tested the hypothesis that vascular smooth muscle cell RyR2s play a specific role in elementary Ca2+ signaling and adaptive vascular responses to vascular pressure and/or flow. Methods and Results Targeted deletion of the Ryr2 gene resulted in a complete loss of sarcoplasmic reticulum-mediated Ca2+-release events and associated Ca2+-activated, large-conductance K+ channel currents in peripheral arteries, leading to increased myogenic tone and systemic blood pressure. In the absence of RyR2, the pulmonary artery pressure response to sustained hypoxia was enhanced, but flow-dependent effects, including blood flow recovery in ischemic hind limbs, were unaffected. Conclusions Our results establish that RyR2-mediated Ca2+-release events in VSCM s specifically regulate myogenic tone (systemic circulation) and arterial adaptation in response to changes in pressure (hypoxic lung model), but not flow. They further suggest that vascular smooth muscle cell-expressed RyR2 deserves scrutiny as a therapeutic target for the treatment of vascular responses in hypertension and chronic vascular diseases.
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PMID:Role of Ryanodine Type 2 Receptors in Elementary Ca2+ Signaling in Arteries and Vascular Adaptive Responses. 3103 May 96