Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005
A study of pemphigus in New Delhi, India, and Oxford, UK, was undertaken including 20 patients in Oxford and 50 in New Delhi. Data included clinical and histological subtypes and socio-economic data; patients were HLA typed. In New Delhi pemphigus vulgaris predominated, but in Oxford pemphigus vulgaris and pemphigus foliaceus have equal prevalence. Disease distribution with sex was the same, but age at onset was significantly lower in New Delhi (p = 0.0019). HLA typing in pemphigus vulgaris patients revealed a significant reduction in HLA-DR2 in New Delhi (p = 0.0008) and Oxford (p = 0.09). A small increase in HLA-DR1 and -DR4 was found in both groups and, in males only, a subtle increase in HLA-DR6 and reduction in HLA-DR3. No differences were found in the class I antigens. Thus there are striking differences in the types of pemphigus between the two populations, yet the genetic predisposition is the same.
We prospectively monitored clinical data and renal function at monthly intervals in 165 patients who had received living-related-donor renal allografts in our institution between January 1981 and December 1991 and had a functioning allograft for 1 year or longer. During a mean follow-up period of 47.2 (range 13-155) months, 32 patients (17.2%) developed late acute rejections, of which 14 (43.7%) were asymptomatic. Amongst the symptomatic late acute rejections, worsening of hypertension was the commonest finding, being present in 11 (61.1%) patients, followed by oliguria in 8 (44.4%) and weight gain in 7 (38.8%) patients. Of these 32 late acute rejections, as many as 28 (87.5%) showed a response to antirejection therapy with high-dose steroids: 5 (15.6%) a complete response and 23 (71.9%) a partial response. The response rate was 100% if it was the first acute rejection (20% complete and 80% partial), 78.6% if it was the second (14.3% complete and 64.3% partial), and no or only a partial response to treatment if it was the third acute rejection episode. On long-term follow-up, patients who had responded to antirejection treatment had a significantly better graft survival as compared with nonresponding patients: 76 and 27%, respectively. Our observations suggest that routine monitoring of the renal function at frequent intervals is essential for early diagnosis and treatment of acute rejections, even during the late posttransplant period. The chances of a response to antirejection therapy are higher during the first episode of late acute transplant rejection as compared with a second or a third late rejection event.
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