Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stroke in children is a relatively uncommon condition and frequently associated with other diseases like cardiopathies, sickle cell disease and chronic smoking. In contrast to stroke in adults, it is rarely caused by atherosclerosis, hypertension or diabetes mellitus. Childhood stroke of unknown causes is called idiopathic stroke. The etiology of idiopathic stroke is unknown. However, several so-called idiopathic diseases develop on the basis of a genetic predisposition. As an approach to investigate this possibility in idiopathic childhood ischemic stroke, we studied the relationship between clinical and immunogenetic features in this disease. We demonstrate that the gene frequencies and relative risk of HLA-B51 were markedly increased in our patients compared with controls (p < 0.001). Thirteen of seventeen HLA-B51-positive patients had had a preceding respiratory infection, which was a higher proportion than in the control group (p < 0.05). In the patient group, the alleles HLA-DRB1*0802, -DRAI*0401 and -DQBI*0402 were also significantly increased, defining the haplotype DRB1*0802-DRA1*0401-DQB1*0402 as a high-risk haplotype for idiopathic childhood ischemic stroke. Transient viral or bacterial infections, which involve vasculitis and vascular occlusion in the brain, can trigger idiopathic childhood ischemic stroke on the basis of an genetic predisposition.
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PMID:Evidence for human leukocyte antigen-related susceptibility in idiopathic childhood ischemic stroke. 1237 32

Atorvastatin and other members of the statin family are widely used for the treatment of hypercholesterolaemia in order to reduce the risk of atherosclerosis and cardiovascular disease. Atorvastatin-induced adverse events are mostly mild and only a few cases of lupus-like syndrome or severe acute hepatitis have been documented. In this case report we describe a patient who developed an atorvastatin-induced severe autoimmune hepatitis. In addition, this patient presented with a concomitant systemic lupus-like syndrome which has been already described for statins but not in association with severe liver disease. Although the drug was immediately withdrawn the disease persisted and even deteriorated to a fulminant disease with evidence of acute hepatic failure. The patient failed to respond to conventional immunosuppression with corticosteroids and azathioprine. Only the introduction of intense immunosuppressive therapy, as used in solid organ transplantation, led to a complete and sustained recovery of the patient. Interestingly, the patient was HLA DR3- and HLA DR4-positive, which are well-known genetic factors associated with autoimmune diseases. This case is the first report of a drug-induced lupus-likesyndrome concomitant with a severe autoimmune hepatitis in a genetically predisposed patient.
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PMID:Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis. 1276 6

Cardiovascular disease is the commonest cause of premature mortality in rheumatoid arthritis (RA) patients. Vascular endothelial injury is the primary event in atherosclerosis. It has been associated with endothelial dysfunction. We have recently observed that actively treated RA patients had endothelial dysfunction. HLA-DRB1 shared epitope alleles, in particular HLA-DRB1*0404, seem to be implicated in the development of endothelial dysfunction. These results underline the influence of genetic factors in the risk of atherosclerosis in RA patients.
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PMID:Endothelial dysfunction in rheumatoid arthritis: influence of HLA-DRB1 alleles. 1524 26

It is well known that subjects with type 1 diabetes are at an increased risk of death from coronary heart disease in comparison to non-diabetic age-matched individuals because hyperglycaemia is believed to be a key risk factor for the development of micro- and macrovascular complications. On the other hand there is increasing evidence about the role of inflammatory mediators in the pathogenesis of atherosclerosis and the development of acute coronary syndromes. It has been recently suggested that IL-18 and sICAM-1 have a strong predictive value for cardiovascular diseases and deaths in patients with coronary artery disease and/or in apparently healthy men. The aim of our study was to estimate the serum levels of IL-18 and sICAM-1 in subjects with type 1 diabetes and their relatives, who share HLA diabetic susceptibility genes (with or without pancreatic autoantibodies), but still without glucose level disturbances, as an evaluation of the possible role of genetic predisposition to the presence of IL-18 in diabetic families. The study was carried out in 35 type 1 diabetic subjects, their 101 healthy first-degree relatives: 36 siblings and 65 parents and the control group consisted of 31 healthy volunteers. We have found increased IL-18 and sICAM-1 levels in subjects with type 1 diabetes and their first degree relatives, who share diabetic HLA haplotypes: DRB1*03/DRB1*04 or DRB1*03/*04/DQB1*02 independently of their autoimmune status. There was a strong positive correlation between IL-18 and sICAM-1 levels in diabetic subjects and their first degree relatives without glucose level disturbances. To our knowledge this is the first study, which suggests that sICAM-1 elevations could be a result of IL-18 overproduction in type 1 diabetic subjects and their first degree relatives. Since in previous studies IL-18 and sICAM-1 were found to be predictors of death in subjects with CHD, one could speculate that high levels of IL-18 observed in subjects with genetic predisposition, but still with normal glucose levels, are an in addition to hyperglycaemia, pathogenic factors responsible for a higher risk of acute coronary events in subjects with diabetes type 1.
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PMID:Interleukin 18 and sICAM-1 serum levels in families with type 1 diabetes mellitus. 1635 56

Posttransplant diabetes mellitus (PTDM) is a frequent complication among renal transplant recipients. This study sought to compare clinical outcomes of patients with PTDM who had strict glucose control with nondiabetic patients and to identify risk factors for atherosclerotic disease in both groups. We retrospectively examined 204 renal allograft recipients transplanted at our center between 1996 and 2002. Demographic features, dialysis and posttransplantation duration, smoking, body mass index, medications, comorbid diseases, number of HLA mismatches, and laboratory parameters including serum levels of creatinine, albumin, calcium, phosphorus, C-reactive protein, lipid parameters, and parathyroid hormone were analyzed as possible risk factors for atherosclerotic disease. Patients were followed for a mean of 59.7 +/- 23.6 months. PTDM was diagnosed according to the American Diabetic Association criteria or the need for an insulin/oral hypoglycemic agent. Twenty-six patients developed PTDM, and these patients had very good diabetes control. One patient with poorly regulated PTDM was excluded. Adverse events which were documented in 24 patients were more frequent among patients with PTDM. Mean age was found to be an independent risk factor for atherosclerotic disease, whereas PTDM was not. There were no differences regarding other atherosclerosis-related or other risk factors (including serum C-reactive protein levels and lipid profiles) between the groups. Nondiabetic subjects tended to have longer graft survival than patients with PTDM, but this finding was not statistically significant. PTDM is an important risk factor for developing atherosclerotic disease. Good control of blood glucose levels can decrease the high morbidity rates and negative influence of PTDM on patient and graft survival rates in this population.
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PMID:Posttransplant diabetes mellitus: Impact of good blood glucose regulation on renal transplant recipient outcome. 1654 67

Epidemiological studies have disclosed an increased mortality due to cardiovascular (CV) complications in patients with rheumatoid arthritis (RA). Patients with this disease have an increased risk of left ventricular diastolic dysfunction and congestive heart failure that is unrelated to the presence of traditional atherosclerosis risk factors or ischemic heart disease. Endothelial dysfunction, an early step in the atherogenesis process, is observed in both early and long-standing actively treated patients with RA. High-resolution B-mode ultrasound studies of the common carotid artery have shown the presence of subclinical atherosclerosis, manifested by increased carotid intima-media thickness and carotid plaques, in patients with RA. Association between HLA-DRB1*04 shared epitope alleles, in particular with HLA-DRB1*0404, and endothelial dysfunction and CV mortality has also been observed in these patients. Chronic inflammation plays a pivotal role in the mechanisms associated with atherogenesis in RA. Tumor necrosis factor (TNF)-alpha is a potent proinflammatory cytokine implicated in the initiation and progression of inflammation as well as in the mechanisms associated with accelerated atherosclerosis in this disease. Anti-TNF-alpha therapy has proved to be clinically effective in patients with severe RA. Recent studies have also emphasized the positive effect of anti-TNF-alpha blockade in improving endothelial dysfunction in RA patients. However, this effect seems to be transient and in line with the persistence of chronic inflammation.
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PMID:Cardiovascular disease in rheumatoid arthritis. 1704 1

Emerging evidence now indicates that the 5-lipoxygenase (5-LO) pathway play a role in the pathogenesis of atherosclerosis and restenosis. The expression of 5-LO by activated macrophages in symptomatic plaques leads to leukotriene B(4) (LTB(4)) accumulation and enhanced synthesis and release of matrix metalloproteinases (MMPs) that can promote plaque rupture. However, the role of 5-LO pathway in diabetic vascular disease has not been previously reported. Thus, the present study was designed to analyze the expression of 5-LO in carotid plaques of diabetic patients and to investigate the possible role of 5-LO pathway in the pathogenesis and progression of diabetic atherosclerosis. Atherosclerotic plaques from 60 patients undergoing carotid endarterectomy were divided into non-diabetic and diabetic group. Plaques were analyzed for 5-LO, MMP-2 and MMP-9 by immunohistochemical, Western blot, and densitometric analyses, whereas zymography was used to detect MMP activity. Immunocytochemistry was also used to identify CD68+macrophages, CD3+T-lymphocytes, and HLA-DR+inflammatory cells. LTB(4) were quantified by enzyme-linked immunosorbent assay. 5-LO showed abundant immunoreactivity in human atherosclerotic carotid lesions, and was colocalized with macrophage infiltrates in atherosclerotic intima. 5-LO expression was higher in diabetic compared with non-diabetic plaques and was associated with increased MMP-2 and MMP-9 expression. Follow-up analyze with zymography assay revealed MMP activity was elevated in diabetic compared with non-diabetic plaques. Notably, in contrast to non-diabetic plaques, LTB(4) levels were significantly increased in diabetic plaques by enzyme-linked immunosorbent assay. These results suggest that overexpression of 5-LO and LTB(4) in atherosclerotic plaques possibly promote MMP-induced plaque rupture in diabetes. Hence, anti-LTs may be useful, not only in reducing atherogenesis, but also in the prevention and treatment of acute atherothrombotic events in diabetic patients.
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PMID:Expanding expression of the 5-lipoxygenase/leukotriene B4 pathway in atherosclerotic lesions of diabetic patients promotes plaque instability. 1782 94

More than 40% of renal allografts show chronic transplant nephropathy (CTN) early after renal transplantation. Cardiovascular disease is the leading cause of death in this population. Thus endothelial dysfunction represents an early angiopathy causing CTN and atherosclerosis. We sought to evaluate changes in endothelial dysfunction and vascular wall thickness during the first year posttransplantation as well as their association with HLA nondependent risk factors for CTN. At 3 and 52 weeks after grafting, we studied 25 patients without overt atherosclerotic disease and acute posttransplant complications for von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), big endothelin-1 (ET-1), flow-mediated dilatation (FMD), intimal media thickness (IMT), serum total cholesterol (TC), and triglycerides (TAG). FMD and IMT at 52 weeks showed significant correlations (P < .05) with recipient age, and the FMD ratios at 3 and 52 weeks correlated with the time on hemodialysis. Recipient age was significantly correlated with TC and PAI-1 with TAG. vWF was the only parameter that significantly correlated with donor age. There were no significant correlations with creatinine clearance. Decreased TAG approached statistical significance (P = .07) and TC decreased nonsignificantly. The worsening of FMD and ET-1 was not significant. A nonsignificant improvement in IMT was not associated with any analyzed parameters. Our results implied that the time on hemodialysis, the presence of hyperlipoproteinemia, and the recipient age significantly contributed to endothelial dysfunction during the first year after transplantation.
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PMID:Significance of HLA nondependent risk factors of chronic transplant nephropathy for the development of endothelial dysfunction after kidney transplantation. 1954 88

Geographic or ethnic differences in the occurrence of disease often provide insights into causes of disease and possible opportunities for disease prevention. A wide variation on the incidence and prevalence of PsA was reported in different countries. The prevalence in China was similar to the rest of the world, whereas the incidence and prevalence of PsA was much lower in Japan. Among patients with psoriasis, 6-42% of the Caucasians were reported to have PsA, but figures were lower from Asian countries (1-9%). Divergent distribution of HLA in different ethnic groups and other genetic determinants may account for these differences in prevalence. PsA affects men and women almost equally in Chinese, Japanese and Iranians, which is similar to their Caucasian counterparts. Polyarthritis developing in the fourth decade was the commonest pattern of arthritis among Chinese, Indians, Iranians, Kuwaiti Arabs and Malays. Arthritis mutilans and eye lesions have rarely been reported in Asian countries. Chinese patients with nail disease and DIP joints involvement have a significantly higher risk of developing deformed joints. More data are required on the safety, efficacy and cost effectiveness of TNF blockers for the treatment of PsA in Asia. Premature atherosclerosis has been recognized as an important co-morbidity in Asian patients with PsA. Increased prevalence of traditional cardiovascular risk factors associated with PsA suggested that the two conditions may share the same inflammatory pathway. Carotid intima-media thickness can identify PsA patients with subclinical atherosclerosis who may benefit from early intervention.
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PMID:Psoriatic arthritis in Asia. 1971 40

Chronic allograft nephropathy (CAN) is a complex phenomenon caused by underlying kidney disease with superimposed enviromental and genetic factors. CAN development begins with progressive renal microvascular injury. Endothelial cells play key roles in the regulation of vascular tone, permeability, and remodeling. A reduction in basal nitric oxide (NO) release as a result of genetic variation in endothelial NO synthase (eNOS) function may predispose to hypertension, thrombosis, vasospasm, and atherosclerosis, all contributing to the development of CAN. We analyzed the G894T mutation at exon 7 of the eNOS gene in relationship to CAN among 81 children with renal transplantations. The 20 patients who developed CAN underwent renal biopsies for histological confirmation. Proteinuria and hypertension were observed in CAN. We selected 173 healthy reference subjects. The G894T polymorphism of the eNOS gene was determined by PCR-restriction fragment-length polymorphism analysis. The group included 33 male and 48 female subjects who received 32 living-related grafts and 49 from deceased donors (DD) donors. Donor age (y) was 32.7 +/- 13.7 and the HLA A,B,DR mismatch number of the cadaveric cases was 3.5 +/- 0.79. The distribution of the genotypes were ENOS GG/GT/TT 48%, 33%, 19%, respectively. G-alleles frequency was 64.8%; T-allele frequency was 35.2%. ENOS G894T gene polymorphism did not seem to influence long-term renal allograft outcome. Recipient ENOS G894T gene polymorphism did not alter the risk of chronic allograft failure. Even if NO synthesis and bioactivity are influenced by this polymorphism, many vasoactive factors may have roles to suppress the advantageous effects of NO.
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PMID:Endothelial nitric oxide synthase (eNOS) gene polymorphism in early term chronic allograft nephropathy. 2000 99


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