Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heterogeneity between two haplotypes in linkage disequilibrium with DR3: B8, C4AQOB1,BfS,DR3 and B18,C4A3BQO,BfF1,DR3, with regard to age at onset of Type 1 (insulin-dependent) diabetes mellitus, was investigated in 325 unrelated French patients (146 males and 179 females, age at onset 1 month to 29 years) who were genotyped for HLA-A, B, C, DR and Bf and 225 of whom were typed for the C4A, B complement components. A subgroup of 82 patients and 75 control subjects were tested for DR beta and DQ beta DNA restriction fragment length polymorphism. The distribution according to age at onset and the mean ages at onset were compared between patients bearing B8, DR3 (n = 58), B18,DR3 (n = 62) or other DR3 haplotypes (Bx, DR3, n = 70), the haplotype segments C4AQOB1,DR3 (n = 41) or C4A3BQO,DR3 (n = 52) and the C4 null alleles C4AQO (N = 48) or C4BQO (n = 112) alone. The B8,DR3 haplotype, its smaller segment C4AQOB1,DR3 or C4AQO alone were associated with age at onset after 6 years (p less than 0.01, less than 0.08 and less than 0.02 respectively); on the other hand, the B18,DR3 haplotype, its segment C4A3BQO,DR3 or C4BQO alone were significantly more frequent in patients aged less than 6 years at onset (p less than 0.02, less than 0.01 and less than 0.01 respectively). Accordingly, the mean age of onset was significantly lower in the latter compared with the former patients (p less than 0.02, less than 0.02 and less than 0.01 respectively). No age-related variation was observed in BX,DR3 patients and their mean age of onset was intermediate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Two distinct HLA-DR3 haplotypes are associated with age related heterogeneity in type 1 (insulin-dependent) diabetes. 290 19

54 normal Caucasian families and 169 families in whom at least one child had type I diabetes (IDDM) were genotyped for HLA-A, B, C, DR and for the complement factors Bf and C4. The paternal and maternal transmission of the different alleles and of haplotypes and complotypes in linkage desequilibrium have been analysed. No distortion of the paternal transmission has been observed in the offspring of the two series of families. On the contrary, a distortion of the maternal segregation of the silent alleles at the complement factor C4A and B locus was found: mothers transmitted C4AQ0 more often than expected to their male offspring (p less than 0.04 in normal families, p less than 0.001 in IDDM families) while they transmitted C4BQ0 in excess to their female offspring (p less than 0.01 and p less than 0.03 in normal and IDDM families, respectively).
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PMID:[Distortion of the maternal segregation of the silent alleles of complement factor 4 in normal and diabetic families]. 309 11

Inappropriate expression of HLA Class II (D/DR) molecules has been detected in the target cells of most autoimmune diseases including Type I (insulin-dependent) diabetes. The possibility that this phenomenon is due to the action of lymphocytes or some of their products has been investigated by analysing in vitro the modulation of HLA products in Beta cells. Monolayer cultures from 25 human pancreatic glands were supplemented with alpha-interferon (IFN), beta-IFN or gamma-IFN, interleukin 2 (IL-2) and supernatants from activated lymphocytes. In addition, lectins and a variety of other hormones, biological products and chemicals were tested. Major histocompatibility complex (MHC) expression was assessed by double immunofluorescence technique using monoclonal antibodies to non-polymorphic determinants of Class I and Class II molecules and the pancreatic cells were identified by antibodies to islet hormones and other cytoplasmic antigens. gamma-IFN and lectins produced a parallel enhancement of HLA-A,B,C expression in islet, exocrine/ductal cells and fibroblasts. HLA-D/DR was inducible in all pancreatic cell types, except endocrine islet cells which did not produce Class II molecules in response to any of the stimuli including supernatants from activated lymphocytes. Exocrine/ductal cells from glands of patients with chronic pancreatitis spontaneously expressed Class II products, but islet cells were devoid of any detectable D/DR. These data are consistent with recent observations which have indicated that in the 'diabetic' pancreas inappropriate Class II expression in the Beta cells occurs independently of the presence of lymphocytes infiltrating the islets, and make it necessary to postulate that other factors are responsible for the Class II induction in Beta cells in human Type I diabetes.
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PMID:Differential expression and regulation of MHC products in the endocrine and exocrine cells of the human pancreas. 309 71

Thirty-one Ethiopian insulin-dependent (or type I) diabetes mellitus (IDDM) patients and thirty-three healthy controls from the same ethnic background were typed for HLA-A, B, C, DR and DQ specificities. The frequencies of both DR3 and DR4 were significantly increased among IDDM patients (resp. p = 0.02, p = 0.01), confirming results in other populations. In contrast to observations in Caucasians, no significant negative association was found with TA10, a newly recognized DQ specificity, at least in the population studied here, whereas DQwl was more frequently observed among healthy controls (p = 0.01). Although this latter difference does not retain statistical significance after correction for the number of comparisons made, these findings may support previous results suggesting the existence of IDDM susceptibility genes associated with DR3 and DR4 and of IDDM resistance genes associated with DQ antigens.
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PMID:HLA-DR and DQ antigens in insulin-dependent diabetics in Ethiopia. 312 28

The salient features of one-year regraft transplant survival are as follows: 1. The effect of cyclosporine is less (about 7% increase in one-year graft survival) on regrafted patients than on first grafts. 2. In general we saw a HLA antigen matching effect in cyclosporine- and noncyclosporine-treated retransplant patients. 3. Patients who received living-related HLA two-haplotype matched kidneys did equally as well as a first or regraft recipient. 4. Transfusions seemed to have a minimal effect on regraft survival. 5. It is more important to match in patients who have PRA and the matching benefits translate into 61% and 75% one-year graft survival for zero DR and zero B,DR mismatched regraft patients, respectively. 6. In regrafts, female donor kidneys resulted in 15% lower one-year graft survival than male donor kidneys. 7. Retransplant patients from fair centers showed a significant 13% increase in one-year graft survival with cyclosporine. 8. Cold ischemia time, diabetes, and kidneys used locally or shipped had little effect on the regraft one-year survival. 9. The initial function of the retransplant kidney had a very large effect on the final one-year graft outcome of that kidney and was independent of the use of cyclosporine patients having a functioning kidney at one month had 75% and 72% one-year regraft survival with and without cyclosporine treatment, respectively. Patients having a nonfunctioning kidney at one month had 5% and 8% one-year regraft survival with and without cyclosporine treatment, respectively. 10. Responder and nonresponder classifications as defined by the duration of the first graft resulted in a 10 to 15% difference in regraft survival. 11. The effect of HLA-A,B matching was very strong in responder patients, i.e., there was a 32% difference in one-year regraft survival between zero mismatch and more than two antigens of mismatch. In nonresponder patients, the effect of HLA-A,B matching was only 5%. For HLA-DR locus matching, the difference was 12% for responders and 6% for nonresponders. 12. Cyclosporine use showed about a 10% increase in graft survival in responders and nonresponders. 13. Responder classification was also possible by separating patients who had initial function but no function at one month (responders) from those with function at one month (nonresponders).
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PMID:Regraft kidney transplant survival. 315 19

After the death of a 12-year old girl with newly discovered insulin-dependent diabetes mellitus, we used monoclonal antibodies in an effort to identify the cells invading the pancreas. The majority of infiltrating lymphocytes were of the T cytotoxic/suppressor phenotype, but other T-cell subpopulations were present. Some of the T cells were "activated" (positive for HLA-DR antigen, and the interleukin-2 receptor). Immunocytes bearing IgG were scattered in the gland, and complement-fixing IgG antibodies were deposited in some islets. Increased expression of Class I (HLA-A, B, and C) molecules was observed in the affected islet cells, and in damaged islets showing scant lymphocytic infiltration, some beta cells (still producing insulin), but not glucagon or somatostatin cells, were HLA-DR positive. The capillary endothelium was markedly dilated and strongly HLA-DR positive. These findings may contribute to an understanding of the sequence of events leading to the destruction of beta cells in classic Type I diabetes mellitus.
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PMID:In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. 315 65

We studied HLA-A, -B, -C, and -DR antigens in 45 patients (from among 34 families), aged 10.2-60 yr, with polyglandular autoimmune disease type I (APG I) and in other family members. HLA-A28 was more frequent in the patients (25%) than in unaffected siblings (16%; P less than 0.05) or in normal Finnish subjects (8.8%; P less than 0.005, corrected P less than 0.2). Compared with the normal subjects, HLA-A28 was more frequent in the patients with hypoparathyroidism (31%; P less than 0.001, corrected P less than 0.04), adrenocortical failure (27%; P less than 0.01), insulin-dependent diabetes mellitus (IDDM; 66%; P less than 0.01), keratopathy (53%; P less than 0.001, corrected P less than 0.04), and alopecia (40%; P less than 0.001, corrected P less than 0.04), but not in the patients with ovarian failure (9%; P = NS). HLA-A28 was more frequent in the patients with hypoparathyroidism (31%) than in APG I patients without it (13%; P less than 0.005, corrected P less than 0.2). It was also more frequent in the patients with IDDM (66%) than in those without it (21%; P less than 0.05). HLA-A3 was more frequent in the patients with ovarian failure (82%) than in APG I patients with normal ovarian function (22%; P less than 0.025) and in normal subjects (45.5%; P less than 0.05). HLA-A9 was less frequent in the patients with ovarian failure (0%) than in those with normal ovarian function (55%; P less than 0.005, corrected P less than 0.2), and it was less frequent (P less than 0.025) in the patients with adrenocortical failure than in those with normal adrenal function. No association was found with any single DR antigen, but of 4 DR-typed IDDM patients, 3 were DR3 or DR4 positive (P = NS). The occurrence of adrenocortical failure, but not hypoparathyroidism, was familial and associated with HLA haploidentity among sets of affected siblings.
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PMID:The expression of autoimmune polyglandular disease type I appears associated with several HLA-A antigens but not with HLA-DR. 316 97

Patients with type I (insulin-dependent) diabetes mellitus maintain B-cell function for a varying period of time after onset. This is commonly held to account for post-initial remission. To estimate residual B-cell function we measured plasma and 24-h urinary C-peptide in 68 type I diabetic patients (age range 4-35 years, within 10-180 days of the onset of symptoms, typed for HLA-A, -B, -C and DR loci. A positive correlation (r = 0.26; p less than 0.05) was found between urinary C-peptide levels and the age of the patient. The analysis of variance of urinary C-peptide values on the basis of the presence or absence of DR3 and DR4 antigens revealed that the DR3-positive patients had reduced excretion (15.2 +/- 9.2 SD micrograms/24h) with respect to the others (22.7 +/- 15.5 SD micrograms/24h) (F = 6.35; p less than 0.05). No interaction effect was found in DR3/4 positive patients. Hence, late onset patients appear to have higher residual C-peptide secretion. In the light of these findings, the assessment of B-cell function and genetic profile may be useful in predicting which patients are likely to have remission periods and identifying the metabolic consequences of even minimal endogenous insulin secretion.
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PMID:Prevalence of residual B-cell function related to age at onset and genetic profile in newly diagnosed type I diabetics. 332 80

The relationship between the HLA system and non-insulin-dependent diabetes mellitus (NIDDM) in South African Indians, a migrant Indian group, was evaluated by testing HLA-A, -B, and -C antigens in 184 patients and 1444 control subjects and HLA-DR antigens in 104 patients and 330 control subjects. There was a significant increase in the frequency of HLA-Bw61 in patients compared with control subjects (27.7 vs. 18%, P = .00155), although the degree of association was not very strong (relative risk 1.7). A similar association has been noted in Fiji Indians, another migrant Indian group. However, no relationship could be established at the DR locus. It is suggested that the relatively high frequency of the Bw61 allele in South African Indians could, in the presence of some environmental factor like obesity, confer increased susceptibility to NIDDM.
Diabetes 1988 Jun
PMID:HLA class I and II antigens in South African Indians with NIDDM. 338 81

The distributions of HLA-A, -B, -(Bw4/Bw6), -C, -DR, -(DRw52/DRw53), and -DQ genes in 19 type I diabetics, 37 type II diabetics, and 13 nondiabetics of the Yoruba tribe in southwestern Nigeria were studied. Because no associations between type II diabetes and HLA were detected in the current study and such associations are not known to exist in most ethnoracial groups, type II diabetics plus nondiabetics were used as a group of controls for the group of type I diabetics. Trends toward associations between increased DR3 (53 versus 30% of controls) and decreased DR2 (21 versus 46% of controls) and type I diabetes were found (0.1 greater than P greater than 0.05). The strongest HLA association with type I diabetes in Caucasians is usually with DR4. The percent of DR4-positive type I diabetes (11%) was not significantly greater that that in the controls (4%). Because the strong HLA associations with type I diabetes in American Blacks are the same as in Caucasians (i.e., increased DR3 and DR4 and decreased DR2), the genetic contribution (i.e., the lack of an association with DR4) to susceptibility to type I diabetes in most Nigerian Blacks may be different from that in most Caucasians and American Blacks. Onset of diabetes in most of the type I subjects was after age 20, and type I diabetics were difficult to recruit for the study, in keeping with reports on the rarity of type I diabetes among Blacks in western Africa and reports of DR4, but not DR3, being correlated with an early age of onset in Caucasians.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 May
PMID:HLA-DR associations in black type I diabetics in Nigeria. Further support for models of inheritance. 345 43


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