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)

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

Published data from literature show a two-to four-fold increase in the incidence of JIDDM, in the Western hemisphere over the past decade (5% to 10-20%). WHO Expert Committee Technical Report Series No. 646 (1980) gives the risk of development of diabetes in the first two decades of life, in the sub-populations of Europe and North America, as 0.1% to 0.3%. In Japan, it is stated to be less than 0.02%; in Tamil Nadu, India, we have calculated the risk to be less than 0.01%. The incidence of JIDDM amongst diabetics in urban Southern India has remained low and static in the last decade; 0.8% and 0.84% in 1973 and 1981 respectively. This is so, despite the fact that infant and perinatal mortality rates over the past two decades have registered a sharp decline in our area. Childhood diabetes and its complications have not shown an uptrend in hospital admissions or infant mortality analysis. It is speculative that our ethnic group is lacks the genetic factor, Bf F1 (which is strongly linked with HLA B18 and IDDM) and the increased association of S1. It remains to be elucidated whether the increased susceptibility to JIDDM of Caucasian children may be associated with a genetic factor or some other exogenous factor, Such as a nutritional factor or virus infection. A plea is made to exchange groups of diabetic children and study the "behavior" of their diabetes under different environments.
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PMID:The significance of certain epidemiological variants in the genesis of juvenile insulin-dependent diabetes mellitus--the need for a global program of co-operation. 668 Apr 82

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

We found the rare properdin factor B(Bf) variant F1 to be present in 11% of 72 patients suffering from insulin-dependent diabetes (IDDM) compared with 2% among 150 normal controls. BfF1 thus confers a relative risk for IDDM of 5.55. All eight patients and three controls who were BfF1 positive were also HLA-B18 positive, reflecting the strong linkage disequilibrium between these two factors. We suggest that BfF1 marks a 'diabetogenic' B18-bearing HLA haplotype. Studies of unselected families with one or more affected members suggest that the B18, BfF1 does not necessarily segregate with IDDM phenotype. This study provides further evidence for the genetic heterogeneity of IDDM.
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PMID:Properdin factor B(Bf) allele BfF1 specifies an HLA-B18 diabetogenic haplotype. 692 67

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

The Basques were previously shown to present a high frequency of HLA-B18 and BfF1, which are known to be associated with insulin dependent diabetes mellitus (IDDM). During the VIII International Histocompatibility Workshop, we studied HLA-A, B, C, DR; Bf, C4 and GLO.I polymorphisms in 51 unrelated French Basque IDDM patients and in 50 controls. Haplotypes were established by family studies in all controls and some patients. Two haplotypes were frequently found in the controls: HLA-A1, Bw57, BfS, C4 F1S, DR7 and HLA-Aw30, Cw5, B18, Bf F1, C4Fs degree, DR3. The first one was not found in the patients. All the components of the second haplotype had increased frequencies possibly as a consequence of linkage disequilibrium with HLA-DR3: a highly significant association between IDDM and HLA-DR3 was observed (90.2% vs 24.0%, relative risk (RR) = 29.1, P less than 10(-11)). The HLA-DR4 frequency was slightly increased (37.3% vs 16.0%), and HLA-DR2 was not found. The silent allele C4s degree was particularly associated with early diagnosed IDDM (86.7% in patients with age at onset under 20 years vs 57.1% in other patients, P less than 0.02). The high relative risk for HLA-DR3/DR4 heterozygous vs that of individuals, possibly HLA-DR3 homozygous, supported the hypothesis that two HLA-DR linked genetic factors could be involved in the inheritance of IDDM susceptibility.
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PMID:HLA-A, B, C, DR antigens, Bf, C4 and glyoxalase I (GLO) polymorphisms in French Basques with insulin-dependent diabetes mellitus (IDDM). 695 94

Fifty-four North Indian patients with Type I (Insulin-Dependent) diabetes mellitus who were aged 30 yr or under at onset were HLA-typed. The frequencies of HLA-BW21, BW35, and A28 were significantly increased and that of HLA-B7 was significantly reduced. On correction for the number of antigens tested, only the difference observed with HLA-BW21 for positive association and B7 for negative association remained statistically significant. HLA-B8, B15 and B18 did not demonstrate any significant association with IDDM in this series of patients. The results of the study further emphasize the well recognized race specificity in HLA antigen distribution in normal population as well as disease states. This association of HLA-BW21 with IDDM is the first report from North India.
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PMID:HLA antigens in type I (insulin-dependent) diabetes mellitus in North India. 702 26

IDDM results from the immune-mediated destruction of pancreatic islet beta cells. Clinicopathologic heterogeneity in IDDM is reflected in part by the wide age range over which the onset of clinical symptoms can occur, after months to years of subclinical "insulitis." Because MHC genes play a critical role in immune function we studied their possible contribution to IDDM heterogeneity by analyzing HLA profiles of 194 IDDM patients in relation to their age at diagnosis. Restriction of HLA-DR heterogeneity was observed in patients diagnosed before age 21 years. Frequencies of DR3 and DR3/4 were highest in the < or = 6-year-old age group and thereafter declined with increasing age at diagnosis. In contrast, the frequency of DR4 remained increased up to age 30 years at diagnosis. DR7, normally considered to be a neutral allele, was like DR2 and DR5, significantly decreased in patients diagnosed before age 21 years. The A30-B18-DR3 haplotype was significantly increased in the < or = 6-year-old age group, A1-B8-DR3 was increased in the > or = 31-year-old group. B62-DR4 was increased only in the > 12-year-old age group. In DR4 patients the frequency of DQ8 was increased across all age groups. A sex difference was observed in those diagnosed at < or = 12 years of age, with an excess of females in the DR3+/DR4- group and males in the DR3-/DR4+ group. An association of DPB1 with IDDM was revealed by an increased frequency overall of DPB1*0301 and/or DPB1*0401, being more pronounced in patients diagnosed at > 20 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA antigens and age at diagnosis of insulin-dependent diabetes mellitus. 774 14


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