Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in the incidence of the HLA system antigens (A1, A2, A3, A9, A10, A11, A19, A28, A29, B5, B7, B8, B13, B14, B15, B16, B17, B18, B21, B22, B27, B35, B37, B40, B41) was studied in 1134 healthy persons and in 147 patients with diabetes mellitus. In comparison with healthy persons, patients with juvenile diabetes mellitus (62) displayed a significant increase in the incidence of antigens B8, B15, B35, and A10, and patients with adult diabetes mellitus with normal weight (35)--of antigen B8. When adult diabetes mellitus was accompanied by obesity (50) a significant rise in the occurrence of antigen A10 was revealed.
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PMID:[Change in the incidence of HL-A antigens in diabetes mellitus]. 615 26

Insulin dependent diabetes mellitus (IDDM) is closely associated with special MHC gene products. The class II gene products, HLA-DR3 and DR4, may be the primary susceptibility genes for IDDM. They mediate the pathogenetical immune mechanisms which, under the additional influence of special MHC-genes of class I and III, lead to diabetes. The extremely high frequency of HLA-DR3, DR4 heterozygotes among diabetic patients and the genetic heterogeneity in B8, DR3 positive patients on the one hand and B15, DR4 positive diabetics on the other with regard to various clinical, epidemiological and immunological parameters, point to the existence of at least two different diabetes susceptibility genes. They act synergistically when they occur together. Thus simple genetic models (autosomal dominant, autosomal recessive, gene dosage) do not appear to be relevant here. The increased diabetic risk for the identical siblings of DR3, DR4-positive patients offers a good opportunity of studying genetically influenced immune deviations in the prediabetic phase which result in the suppression and destruction of Beta cells and finally in the manifestation of diabetes.
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PMID:The HLA association of insulin-dependent (type I) diabetes mellitus. 633 38

HLA in 12 unrelated Chinese paediatric patients with insulin dependent diabetes mellitus (IDDM) were found to have an increased frequency of BW22, B17 and AW33. BW22 was observed in 5/12 (41.7%) of IDDM patients compared to 40/330 normal unrelated Chinese controls (p less than 0.005, rr = 5.2). AW33 and B17 were observed in 6/12 (50.0%) and 7/12 (58.3%) of IDDM patients respectively, compared to 36/330 and 46/330 in the normal controls respectively (AW33: corrected p less than 0.0026, RR = 8.2, B17: corrected p less than 0.0026, rr = 8.6). HLA B8, B15 and B18 did not demonstrate any significant association with IDDM in this series of patients. The results of this study further emphasize the well recognized race specificity in HLA antigen distribution in normal population as well as disease states.
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PMID:HLA system in Chinese children with insulin-dependent diabetes mellitus. 634 63

Present knowledge regarding the HLA system and the association between HLA antigens and insulin-dependent type 1 diabetes mellitus (IDDM) is reviewed. The heterogeneity of diabetes, immunogenetically speaking, is emphasized. Results are reported for HLA typing in 18 cases of known IDDM recently diagnosed and observed at the Karen Bruni Diabetes Center in approximately one year (1981-82). The frequency of HLA antigens B7, B8 (in linkage disequilibrium with DR3), B15 (in linkage disequilibrium with DR4) and B18 was examined in comparison with a Piemontese control group. The X2 method was used for calculating the relative risk and statistic importance of the intensity of association. IDDM susceptibility in association with HLA-B18 was confirmed and resulted significantly higher in our cases in respect to controls. Correlations without, however, reliable importance, have also been found between HLA-B8 and B15. IDDM protection by HLA-B7 was not confirmed. Diabetes began during the winter, from October to February, in 10 out of 18 cases, and some were positively related to a previous respiratory viral infection. Previous virus infection was found in three B7-positive cases. The more frequent arousal of diabetic symptoms during the winter in subjects positive for HLA-B8 and B18 was confirmed in 7 out of 8 cases. This work demonstrates the current practicability of HLA typing of recently diagnosed insulin-dependent diabetic in a Diabetes Center. This element helps to a more correct classification--on a subclinical basis--of initial cases of type 1 and 2 diabetes and can be used for possible problems during the course of insulin therapy.
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PMID:[The HLA system and insulin-dependent diabetes mellitus. A review and personal studies]. 638 59

In order to try to detect heterogeneity within insulin dependent diabetes mellitus (IDDM) and to distinguish a mode of inheritance of IDDM, population genetic analyses were performed using HLA allele frequencies. HLA-A and -B typing performed on 231 IDDM individuals and 268 controls from the southeastern U.S. showed significant increases with IDDM in A2, B8, B15 and B18, and significant decreases in Aw23, B7, B14 and B17. The combination of HLA-B8/B15 showed a greatly increased risk (RR = 25.5). Between the 120 IDDM individuals and 123 controls HLA-DR typed, HLA-DR3 and -DR4 were significantly increased among the IDDM group and DR2 and DR7 were decreased. The risk for DR3/4 was 29.2. It appeared that the B15 association was secondary to the DR4, but the B8/DR3 association showed no difference. Using the method of Curie-Cohen, no significant increases in risk were found for the B8/B15 or DR3/DR4 heterozygotes when compared to the respective homozygotes. Using the method of Thomson and Bodmer, the dominant mode of inheritance was excluded for DR4 only. There was a significant increase in B15 and DR4 in those with onset before age 20. No significant differences were found among the DR phenotypes with respect to season.
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PMID:Population genetic analyses of insulin dependent diabetes mellitus using HLA allele frequencies. 641 98

The typing of 22 HLA-A and B antigens in members of 13 families with one child having juvenile diabetes mellitus showed a statistically significant higher frequency of HLA-B8 antigen in sick children (51.54%) as well as high parental heredity rate of this antigen, as compared to 301 normal subjects and 51 normal children of families free from diabetes mellitus. The agreement of 85.71% in one or two haplotypes in diabetic and healthy siblings in 7 families involved antigens other than B8. The results of these family studies confirm the existing relationship between HLA-B8 and juvenile diabetes mellitus as demonstrated by repeated screenings of the patients populations. The relationship of HLA antigens to insulin-dependent juvenile diabetes mellitus has been studied by many authors. The issues of their studies on patient populations revealed HLA-DR3, Dw3, DR4, Dw4, B8, B18, B15, B40, Cw3 and secondarily A1 and A2 to occur with significantly higher frequency. On the other hand, antigens DR2, Dw2, B7 (secondarily A3 and A11) are statistically less frequent in this disease, and their presence therefore means a certain protection against the risk of diabetes (4, 6, 7, 11, 15, 21). Individual authors' family studies differ in conclusions as to the occurrence of some of the above HLA antigens, and the degree of HLA identity of two siblings, one with diabetes, the other one normal (6, 8, 12, 17). For this reason we decided to start investigations on the occurrence of HLA A and B antigens in family members with one child having juvenile diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA and insulin-dependent juvenile diabetes mellitus. 641 92

Two hundred subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were typed for HLA-B, HLA-DR, and properdin factor B (Bf). HLA and Bf antigen and haplotype frequencies in subjects were compared with control frequencies derived from the 8th HLA Workshop. Frequencies of extended haplotypes (defined by B-Bf-DR alleles on a chromosome) were also contrasted with control frequencies. Significant positive associations between IDDM and HLA-B8, DR3, DR4, BfS, and BfF1 were confirmed, as were significant negative associations between IDDM and HLA-B7, DR2, DR5, DR7, and BfF. One haplotype (B7-BfS-DR2) exhibited significant negative association, while five haplotypes (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4) exhibited significant positive associations with IDDM. In this sample, 64% of all probands carried at least one of the high-risk haplotypes. In conclusion, the occurrence of five "high-risk" haplotypes associated with IDDM provides evidence for previously undocumented genetic heterogeneity and suggests that possibly more than two HLA-region genes may be involved in IDDM susceptibility.
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PMID:Genetic heterogeneity of insulin-dependent (type I) diabetes mellitus: evidence from a study of extended haplotypes. 659 40

We have studied major histocompatibility complex markers in Caucasian patients with type I diabetes mellitus and their families. The frequencies of extended haplotypes that were composed of specific HLA-B, HLA-DR, BF, C2, C4A, and C4B allelic combinations, which occurred more commonly than expected, were compared on random diabetic and normal chromosomes in the study families. We demonstrated that all of the previously recognized increases in HLA-B8, B18, B15, DR3, and perhaps DR4 could be ascribed to the increase among diabetic haplotypes of a few extended haplotypes: [HLA B8, DR3, SC01, GLO2]; [HLA-B18, DR3, F1C30]; [HLA-B15, DR4, SC33]; and [HLA-BW38, DR4, SC21]. In fact, HLA-DR3 on nonextended haplotypes was "protective", with a relative risk considerably less than 1.0. There was a paucity or absence among diabetic patients of several extended haplotypes of normal chromosomes, notably [HLA-B7, DR2, SC31] and [HLA-BW44, DR4, SC30]. The extended haplotype [HLA-BW38, DR4, SC21] is found only in Ashkenazi Jewish patients, which suggests that extended haplotypes mark specific mutations that arise in defined ethnic groups. The data show that no known MHC allele, including HLA-DR3 and possibly HLA-DR4, is per se a marker for or itself a susceptibility gene for type I diabetes. Rather, extended haplotypes, with relatively fixed alleles, are either carriers or noncarriers of susceptibility genes for this disease. Thus, the increased frequency (association) or the decreased frequency (protection) of individual MHC alleles is largely explainable by these extended haplotypes.
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PMID:Extended major histocompatibility complex haplotypes in type I diabetes mellitus. 674 3

The association between insulin dependent diabetes mellitus (IDDM) and the HLA system was studied in two groups of Jewish patients: 50 Ashkenazim and 42 non-Ashkenazim. The pattern of association of HLA-A and B locus antigens was somewhat different from that observed in European Caucasian patients. HLA-B8 had a higher frequency; B15 and Cw3 were rare in the population studied and were less frequent in IDDM patients than in controls. On the other hand, the frequency of A26, B18, and Bw38 was increased in Ashkenazi patients, but not in non-Ashkenazim, who in turn showed an increase for Bw51. Although the association between IDDM and HLA-A and B locus antigens shows a marked variability in different populations, the association with HLA-DR3 and DR4 is constant feature. There was a typical excess of DR3/DR4 heterozygotes in both patient groups. This heterozygote type carries the highest relative risk, followed by DR4/DR4 homozygotes. These data can well be interpreted by a model of two different HLA-linked susceptibility genes, one associated with DR3 and the other one with DR4, that interact so that different genotypes are associated with different levels of penetrance. This model received further support from studies in 15 multiple case families where there is an excess of affected sib pairs sharing two DR antigens.
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PMID:Genetics of insulin dependent diabetes mellitus in Israel: population and family study. 694 99

Seventy-four North American Caucasian insulin dependent diabetics are presented and compared to 100 healthy controls relative to HLA-A and B locus antigens. A highly significant increase in the frequency of HLA-B8 was found (p < 0.01, relative risk 3.67). The presence of HLA-A11 conferred statistically significant protection against disease development in these patients (p < 0.01, relative risk 0.19). There was no significant difference in the frequency of HLA-B7, B8, or B15 between the study and control groups. The patient group does show a significant increase in heterozygosity for HLA-B8 and HLA-B15 when compared to healthy controls (p < 0.05, relative risk 7.17). Increased incidence of HLA-B18 has previously been noted in French and English populations only. Since most of our HLA-B18 patients are of English extraction, it is concluded tht the altered incidence of the HLA-B18 allele in insulin dependent diabetes does persist in this migratory European population.
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PMID:Decreased incidence of HLA-A11 and increased incidence of HLA-B8 in a North American population of insulin dependent diabetics. 700 49


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