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)

Haplotypes including HLA, Bf and C4 loci were analyzed in a material comprising 55 families with diabetic children. One hundred and ten haplotypes found in IDDM patients were compared with 101 haplotypes present only in healthy family members. Two complotypes, BfSC4A3B3 and SC4A0B1, were significantly more common (P less than 0.05) in the diabetic haplotypes, and these were in most cases found in haplotypic combinations with HLA-B15,Dw4,DR4 and HLA-B8,Dw3,DR3 genes, respectively. The B8/DR3 haplotype was better conserved, as 72% included the BfSC4A0B1 complotype as compared with only 35% of the B15/DR4 haplotypes with "high risk" C4A3B3 complement alleles (p less than 0.05). DR3 was found in 26% of the diabetic haplotypes and DR4 in 43%. DR4 associated with the Dw4 in 69% of cases and with Dw14 in 26% of the diabetic haplotypes. Our results confirm that the two phenotypes found earlier to be associated with IDDM in Northern Finland, e.g. "B15,BfS,C4A3B3,Dw4,DR4" and "B8,Bfs,C4A0B1,Dw3,DR3" are inherited as haplotypes.
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PMID:Extended HLA haplotypes in families with insulin-dependent diabetes mellitus in northern Finland. 321 30

Type 1 diabetes is said to be extremely rare in children in India, where diabetes treated with insulin may be due to chronic pancreatic disease or malnutrition. To see whether typical type 1 diabetes occurred in Asian children in the United Kingdom, all known Asian children with diabetes in industrial West Yorkshire were ascertained. A total of 17 such children were studied; of these, seven were from three multiplex families and two fathers from these families had diabetes. All children were ketosis prone and developed diabetes while resident in the UK. There were significant increases in HLA-B8 and HLA-DR3 and increases in HLA-DR4 and HLA-DR3/DR4, while HLA-B15 was absent. Islet cell antibodies, either IgG or complement fixing, were present in four of 18 subjects tested, all of whom had disease of short duration. The prevalence of type 1 diabetes in Asian children aged 15 years or less in West Yorkshire was 36/100,000, assuming complete ascertainment. It is concluded that typical type 1 diabetes may occur in Asian children and this condition may be more common in families who have migrated to the UK.
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PMID:Insulin dependent diabetes in Asians. 349 31

The distribution of major histocompatibility complex (MHC) phenotypes in unrelated patients with Graves' disease or Type I diabetes mellitus and healthy controls was examined. HLA-B8 was increased in both the Graves' disease patients (p = .0018) and diabetes mellitus patients (p = .0246) relative to controls. Although C4A*QO is known to show strong linkage disequilibrium with HLA-B8, we could not demonstrate a difference in the frequency of this allele between either group of patients and the controls because the null C4A*QO cannot be accurately estimated from phenotype data. An unusual variant C4B*3 occurred three times in 117 controls, 10 times in 61 Graves' disease patients (p = .0012) and 13 times in 48 diabetic patients (p = 0.74 X 10(-5]. Although C4B*3 is known to show strong linkage disequilibrium with HLA-B15, the frequencies of B15 in the two patient groups did not differ from that of the controls considered here. When 28 MHC haplotypes (supratypes) from 14 unrelated patients with Type I diabetes were compared with 27 non-diabetes supratypes occurring in the same families but not in the patients, 8/28 Type I diabetes supratypes were C4AQOB1+, HLA-B8+, and 4/28 were C4B*3+, whereas 1/27 non-diabetes supratypes was C4AQOB1+, B8+, and 0/27 was C4B*3+. Of the four C4B*3+ diabetes positive supratypes, two were HLA-B15, one was B5 and one was B40. Finally, the second haplotype of 11 diabetes mellitus patients known to carry one high risk C4 haplotype was investigated. The second haplotype was the common type C4A3B1 in only 3/11, whereas at least 5/11 had second haplotypes containing C4B*QO, C4B*3, C4B*2 or C4A*4.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polymorphism of the fourth component of complement in Graves' disease and type I diabetes mellitus. 386 86

The diversity of HLA antigens frequencies associated with Insulin Dependent Diabetes Mellitus (IDDM) reported in different populations raised the importance of determining HLA-A, -B and -C specificities in patients with IDDM in the Egyptian population. The study has been carried out on thirty patients with IDDM and thirty healthy control subjects matched for age and sex as patients included in the study. The results of the present work showed that patients with IDDM showed a significant increase in frequency of HLA-A2, HLA-B8 and HLA-B15. These findings are in accordance with the genetic heterogeneity of IDDM which is in turn in harmony with the modern concept on the complex aetiology of the disease. On the other hand, HLA-A3, HLA-B5 and HLA-B7 have been found significantly decreased in patients with IDDM, thus suggesting that these alleles may confer a protective effect from acquiring the disease. When HLA specificities have been studied in relation to the age of onset of the disease, HLA-A29 have been found in higher frequency in the age group after 15 years, while HLA-B15 in that before 15 years. This variability may be related to variation in the viral agents responsible for the infectious mechanism.
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PMID:HLA-A, -B and -C specificities in insulin dependent diabetes mellitus in the Egyptian population. 387 1

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

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

Subtypes of HLA-DR4 are associated with susceptibility or protection against type 1 diabetes (T1DM). We addressed whether this reflects linkage disequilibrium with the true susceptibility locus by studying broader MHC haplotypes marked by alleles of HLA-B, IKBL (adjacent to TNFA) and complement C4. The study used a largely Caucasian cohort from Western Australia. HLA-DRB1*0401 and HLA-DRB1*0405 marked susceptibility to T1DM. In Caucasians, DRB1*0401 occurs predominantly in the 44.1 ancestral haplotype (AH; HLA-A2,B44, DRB1*0401,DQB1*0301) and the 62.1AH (HLA-A2,B15(62),DRB1*0401,DQB1*0302). HLA-B15 marked susceptibility and HLA-B44 marked with resistance to T1DM in patients and controls preselected for HLA-DRB1*0401. A gene between TNFA and HLA-B on the 8.1AH (HLA-A1,B8,;DR3,DQ2) modifies the effects of the class II alleles. Here, alleles characteristic of the 62.1AH (C4B3, IKBL+446*T and HLA-A2,B15) were screened in donors preselected for HLA-DRB1*0401. C4B3 was associated with diabetes, consistent with a diabetes gene telomeric of MHC class II. However, increases in carriage of IKBL+446*T and HLA-A2,B15 were marginal, as too few control subjects were available with the diabetogenic alleles. However, with these tools, selection of HLA-DRB1*0401, DQB1*0302 donors who are positive and negative for C4B3 will allow bidirectional mapping of diabetes genes in the central MHC.
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PMID:Does a central MHC gene in linkage disequilibrium with HLA-DRB1*0401 affect susceptibility to type 1 diabetes? 1585 1