Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus

Article Abstract:

Part of the function of the immune system is regulated by the human leukocyte (white blood cell) antigens (HLA), which lie on a particular region (locus) of chromosome 6. Genetic variations (alleles) that result in HLA proteins of slightly different structure have been associated with susceptibility to insulin-dependent diabetes mellitus (IDDM). The HLA region associated with this disorder is the HLA Class II antigen DQ site. Using allele-specific oligonucleotides (a method of evaluating DNA), investigators determined the HLA-DQ haplotypes (the alleles on one of the paired chromosomes) of blood cells from 284 unrelated white IDDM patients and 203 white control subjects. The results revealed that the frequency of HLA-DQ alleles differed between IDDM patients and control subjects. Only 2.3 percent of the IDDM patients possessed the HLA-DQw1.2 allele, compared with 36.4 percent of the controls. On the other hand, HLA-DQw8 appeared more frequently among IDDM patients (35.7 percent) than among normal subjects (10.1 percent). The presence of aspartic acid at position 57 on one of the HLA-DQ protein chains (the beta chain) seemed to confer protection against IDDM; almost all the IDDM patients had at least one allele without it, while only 24 percent of the normal subjects lacked aspartic acid at this site. When the risk for IDDM was calculated according to HLA-DQ subtype frequency, it appeared that 11 haplotypes were 'protective'; many of these were DQw1.2. Haplotypes that were at high risk for IDDM were primarily HLA-DQw8. Both protection and susceptibility seemed to be conferred by the presence of these haplotypes, regardless of the other allele the person had inherited. However, since people who had both HLA-DQw1.2 and HLA-DQw8 had a relative risk of only 0.37, it was concluded that the protective effect dominated over susceptibility. While previous research has demonstrated these associations, the large number of patients, and the methods used here, were unique. An evaluation of the concept of protective effects is provided. Overall, the findings demonstrate that the method used can provide important information regarding DQ types and IDDM susceptibility. (Consumer Summary produced by Reliance Medical Information, Inc.)

Risk factors, Diabetes, Diabetes mellitus

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Association of primary sclerosing cholangitis with HLA-DRw52a

Article Abstract:

A set of genes on chromosome 6 that are important in the functioning of the immune system are those which code for the human leukocyte antigens (HLA). Genetic variations (alleles) that result in HLA proteins of slightly different structure have been associated with susceptibility to a variety of diseases, although only three have been identified in which all patients have the same HLA antigen. These are ankylosing spondylitis; pemphigus vulgaris (a skin disorder); and narcolepsy (a chronic disease with attacks of sleep). To see whether specific HLA haplotypes (genetic sequences on one of the two paired chromosomes) are associated with primary sclerosing cholangitis (a condition in which the bile ducts become inflamed and hard), tissue typing was performed for 29 patients with this disorder and a large number of blood donors (to determine the frequency of alleles in the general population). Since the diagnoses of primary sclerosing cholangitis and primary biliary cirrhosis can be confused, 35 patients with primary biliary cirrhosis were also included in the study. The presence of several antigens at the A, B, and DR loci (regions within the HLA locus) were evaluated. Results showed that all patients with primary sclerosing cholangitis had the DRw52a antigen, which was present in only 35 percent of controls. One haplotype (A1,B8,Cw7,DRw17,DQw2,DRw52a) appeared in 15 patients, 12 of whom also had ulcerative colitis. The frequencies of the most important antigens are presented in a table. The association between HLA haplotypes and primary biliary cirrhosis was weak. The frequency of certain HLA haplotypes among patients with diverse diseases suggests that the genetic predisposition may exist for a certain kind of abnormality, with the actual target organ a function of environmental effects, or the effects of another gene. These findings demonstrate that it is possible to identify specific sites on the HLA molecule which seem to confer susceptibility to primary sclerosing cholangitis. (Consumer Summary produced by Reliance Medical Information, Inc.)

Diagnosis, Cholangitis

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Antibodies against MICA antigens and kidney-transplant rejection

Article Abstract:

The immune response to (MICA) antigens were studied to determine their role in the failure of kidney allografts. The study evidence suggest that sensitization against MICA antigens before transplantation was associated with decreased renal-allograft survival.

Science & research, Research, Graft rejection, Kidneys, Kidney transplantation, Antigen-antibody reactions, Clinical report

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