Simple tandem repeat polymorphisms in the neuronal nitric oxide synthase gene in different ethnic populations.
(65/11846)
Allelic frequencies of a CA dinucleotide repeat in exon 29 and an intronic AAT trinucleotide repeat in the neuronal nitric oxide synthase (NOS1) gene were determined by simple sequence length polymorphism (SSLP) in 305 American-Caucasian and 105 African-American healthy subjects. There were highly significant differences in allele frequencies between the two ethnically diverse study populations. (+info)
New AccI polymorphism in the follicle-stimulating hormone beta-subunit gene and its prevalence in three Southeast Asian populations.
(66/11846)
A thymine-cytosine substitution was identified in exon 3 (codon 76, TAT to TAC) of the human follicle-stimulating hormone (FSH) beta-subunit gene. The nucleotide change led to creation of an AccI digestion site. The frequencies of the A allele (with AccI site) in Chinese (n = 201), Malays (n = 168) and Indians (n = 132) were 0.358, 0.333 and 0.402, respectively. The new FSH beta-subunit marker may be useful in gene tracking and association studies. (+info)
Association of polymorphism in glutathione S-transferase loci with susceptibility and outcome in rheumatoid arthritis: comparison with the shared epitope.
(67/11846)
OBJECTIVE: To determine whether glutathione S-transferase GSTM1, GSTM3, GSTT1, and GSTP1 genotypes influence susceptibility or outcome in rheumatoid arthritis (RA). METHODS: 277 RA patients were compared with 577 controls to examine any associations between GST genotypes and susceptibility to RA. The effect of genotypes on outcome (Larsen and functional scores) and time integrated acute phase responses (erythrocyte sedimentation rate and C reactive protein) was assessed in 122 patients with disease duration of 5-10 years. GST and HLA-DRB1 genotypes were determined using polymerase chain reaction based assays. Data were analysed using multiple regression analysis with correction for age, sex, disease duration, and the DRB1 associated shared epitope (SE) and rheumatoid factor (RF) positivity where appropriate. RESULTS: The GSTM1*A/*B genotype was less common in RA cases (3 of 276) than in controls (22 of 591) (exact p = 0.047), though significance was lost when adjustment was made for multiple comparisons. The Larsen score was higher (p = 0.039) in the GSTM1 null patients (89.9) than those with other GSTM1 genotypes (74.7), and this was independent of the SE. Again, correction for multiple testing resulted in loss of significance. The difference in Larsen scores between patients homozygous or negative for the SE (87.9 v 74.3) was similar to that between GSTM1 null and non-null patients. No associations between GSTM3 or GSTT1 genotypes and disease markers were identified although the association between GSTP1*B/*B and Larsen score approached significance (p = 0.096). CONCLUSION: It is proposed that certain GSTs may influence susceptibility and radiological progression in RA and that this is independent of the effect of the HLA-DRB1 associated SE. The mechanism for this effect is presumed to be because of differences in the ability of various GST enzymes to utilise the cytotoxic products of oxidant stress. Although significance was lost after correction for multiple testing, the data indicate that further studies may be of value in RA to determine the influence of the GST and other genes involved in cellular protection against oxidative stress. (+info)
The A-G polymorphism in exon 1 of the CTLA-4 gene is not associated with systemic lupus erythematosus.
(68/11846)
OBJECTIVES: Factors contributing to the development of systemic lupus erythematosus (SLE) remain largely unknown although are likely to include both environmental and genetic components. Studies on murine lupus have indicated a role for an antibody that blocks binding of cytotoxic T lymphocyte associated-4 (CTLA-4) to B7 on antigen presenting cells in the treatment of disease, suggesting that CTLA-4 may play an important part in the disease process. This study, therefore, investigated the frequency of a previously described A-G polymorphism in exon 1 of the CTLA-4 gene, the G allele of which has shown to be associated with both Graves' disease and type I diabetes, to determine whether this polymorphism was playing a part in the development of SLE. METHODS: One hundred and twenty six SLE patients and 363 control subjects were genotyped for the A-G polymorphism in exon 1 of the CTLA-4 gene. Target DNA was amplified using the polymerase chain reaction and the resulting product was digested using the BbvI restriction enzyme. RESULTS: No differences in allele or genotype frequencies were observed between patients with SLE and control subjects. CONCLUSION: These data suggest that the A-G polymorphism in exon 1 of the CTLA-4 gene does not play a part in the genetic susceptibility to the development of SLE. (+info)
Asymptomatic bronchial hyperresponsiveness to exercise in childhood and the development of asthma related symptoms in young adulthood: the Odense Schoolchild Study.
(69/11846)
BACKGROUND: Exercise testing may be of value in identifying a group of children at high risk of subsequently developing respiratory symptoms. As few longitudinal studies have investigated this issue, the bronchial hyperresponsiveness to exercise in asymptomatic children was evaluated as a risk factor for developing asthma related symptoms in young adulthood. METHODS: A community based sample of 1369 schoolchildren, first investigated in 1985 at a mean age of 9.7 years, was followed up after a mean of 10.5 years. Nine hundred and twenty children (67%) were asymptomatic in childhood and 777 (84.9%) of these were re-investigated at follow up. At the first examination a maximum progressive exercise test on a bicycle ergometer was used to induce airway narrowing. The forced expiratory volume in one second (FEV1) after exercise was considered abnormal if the percentage fall in FEV1 was more than 5% of the highest fall in the reference subjects characterised by having no previous history of asthma or asthma related symptoms. The threshold for a positive test was 8.6% of pre-exercise FEV1. RESULTS: One hundred and three subjects (13%) had wheeze within the last year at follow up and, of these, nine (9%) had been hyperresponsive to exercise in 1985. One hundred and seventy subjects (22%) had non-infectious cough within the previous year, 11 of whom (6%) had been hyperresponsive to exercise in 1985. Multiple regression analysis showed that subjects with hyperresponsiveness to exercise had an increased risk of developing wheeze compared with subjects with a normal response to exercise when the fall in FEV1 after exercise was included as a variable (threshold odds ratio (OR) 2.3 (95% CI 1.1 to 5.5)). The trend was not significant when exercise induced bronchospasm was included as a continuous variable (OR 1.02 (95% CI 0.97 to 1.06)). CONCLUSIONS: Asymptomatic children who are hyperresponsive to exercise are at increased risk of developing new symptoms related to wheezing but the predictive value of exercise testing for individuals is low. (+info)
Prevalence of atopy, asthma symptoms and diagnosis, and the management of asthma: comparison of an affluent and a non-affluent country.
(70/11846)
BACKGROUND: The prevalence of childhood asthma and of atopy varies widely between countries. However, few studies have compared the pattern of diagnosis and management of asthma, or the role of atopy in predisposing to asthma between a less affluent country and a more affluent country. The aim of this study was to compare the prevalence of symptoms, diagnosis, and management of asthma, and the prevalence of atopy as measured by skin prick tests in Nigeria and Australia using a standardised methodology. METHODS: Respiratory history was collected using a validated questionnaire administered to parents, and atopy was measured with skin prick tests in 654 Australian and 566 Nigerian children aged 8-11 years (70% consent rate in Australia, 60% in Nigeria). RESULTS: Wheeze and persistent cough were less prevalent in Nigeria (10.2% and 5.1%, respectively) than in Australia (21.9% and 9.6%, respectively), caused less morbidity, and were less likely to be labelled or treated as asthma than in Australia. There was no significant difference in the overall prevalence of atopy between the two countries (Australia 32. 5%, Nigeria 28.2%). Atopy was a strong risk for wheeze in both countries (odds ratio (OR) 3.4 (95% CI 2.3 to 5.1) in Australia, 1.8 (95% CI 1.0 to 3.3) in Nigeria), especially atopy to house dust mites (OR 3.1 (95% CI 2.1 to 4.7) in Australia, 2.4 (95% CI 1.3 to 4. 3) in Nigeria). CONCLUSION: Although there was a similar prevalence of atopy in both countries, Australian children had a higher prevalence of asthma symptoms. Further studies are needed to determine why atopic children in Australia are more at risk of developing asthma. Such studies will have important implications for the prevention of asthma. (+info)
Ten year survival after heart transplantation: palliative procedure or successful long term treatment?
(71/11846)
OBJECTIVE: To investigate the long term outcome and prognostic factors after heart transplantation. SETTING: University hospital. SUBJECTS: 120 heart transplant patients (98 male, 22 female; underlying disease: dilated cardiomyopathy in 69, coronary artery disease in 42, miscellaneous in nine) who had undergone heart transplantation between October 1984 and October 1987. Immunosuppressive treatment was comparable in all patients and rejection episodes were treated in a uniform manner. METHODS: Functional status, quality of life, and potential predictors for long term survival were investigated. RESULTS: Actuarial survival rates were 65% at five years and 48% at 10 years; 58 patients survived > 10 years. The major causes of death were cardiac allograft vasculopathy (39%), acute rejection (18%), infection (11%), and malignancy (11%). Long term survivors had good exercise tolerance assessed by the New York Heart Association classification: 47 (81%) in grade I/II; 11 (19%) in grade III/IV. Echocardiography showed good left ventricular function in 48 patients. On angiography, severe allograft vasculopathy was present in only 16 patients (28%). Renal function was only slightly impaired, with mean (SD) serum creatinine of 148.5 (84.9) micromol/l. Multiple potential predictors of long term survival were analysed but none was found useful. CONCLUSIONS: Heart transplantation represents a valuable form of treatment. Survival for more than 10 years with a good exercise tolerance and acceptable side effects from immunosuppression can be achieved in about 50% of patients. (+info)
Clinical outcome of patients treated with spinal cord stimulation for therapeutically refractory angina pectoris. The Working Group on Neurocardiology.
(72/11846)
OBJECTIVE: To determine morbidity and mortality characteristics in patients treated with electrical neuromodulation for refractory angina pectoris. DESIGN: A retrospective multicentre study of patients treated with spinal cord stimulation between 1987 and 1997; 21 centres were contacted and 14 responded. SETTING: Specialist centres worldwide. PATIENTS: Questionnaires were returned on 517 patients, of whom 71% were male. One was lost to follow up. Mean (SD) age was 63.9 (10.1) years. Duration of angina pectoris was 8.1 (6.3) years. RESULTS: Before spinal cord stimulation, 66% of the patients had experienced myocardial infarction, 68% had three vessel disease, and in 24% the left ventricular ejection fraction (LVEF) was /= 71 years were independent predictors of mortality. During spinal cord stimulation, New York Heart Association functional class improved from 3.5 to 2.1 (p < 0.01); 25 of the deceased patients (24%) and 32 survivors (8%) experienced myocardial infarction; hospital admissions were significantly (p < 0.001) more common in the deceased group (66% v 37%). CONCLUSIONS: The clinical outcome of patients with intractable angina is not adversely affected by the chronic use of neurostimulation. (+info)