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

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.
 ...
PMID:[The HLA system and insulin-dependent diabetes mellitus. A review and personal studies]. 638 59

The literature of the past ten years shows that the introduction of highly purified heterologous and, lastly, homologous insulins has notably lowered the production of IgG and IgE specific insulin antibodies, but has not succeeded in completely eliminating clinical manifestations of the immune or hyper-immune response to insulin therapy. In particular, insulin allergy with or without lipodystrophy is still seen. Among the factors of insulin immunogenicity, there is a possible genetic control of the immune response in type I diabetes: determining HLA halloantigens (A, B, C, D) might identify specific immune response genes (Ir genes). Initial researches, performed until now almost exclusively upon diabetics treated with conventional heterologous insulin, seem to indicate a positive relationship between haplotype HLA - B15 - DR4 and an elevated immune response, whereas haplotypes HLA - B8 - DR3 and HLA - B18 - DR3 might protect against the formation of anti-insulin antibodies. Antigens D/DR3 and D/DR4 are known to be primitively associated to susceptibility for type I diabetes, whereas antigens B8, B15, B18 are secondarily associated to the rise in frequency of DR3 and DR4 for the "linkage disequilibrium" existing between alleles of B and D loci. The results of HLA typing are presented in 2 groups of insulin-dependent diabetics (ID) followed from an immunological viewpoint during therapy with monocomponent heterologous insulin for over 5 years. The first group is composed of 50 patients with low IgG anti-insulin antibody titers (less than 1 mU/ml, Christiansen: low responders); the second group is made up of 23 patients with high IgG anti-insulin antibody titers (greater than 2.5 mU/ml, Christiansen: high responders) and includes 5 subjects with insulin allergy (associated or not with insulin lipoatrophy) and high levels of insulin specific IgE antibodies. A study of the frequencies of various HLA-B antigens in both groups of patients, in regard to a control group of piemontese population, in relation to the intensity of association (relative risk) and to the statistical importance of frequencies, shows only a possible protective effect of the HLA-B18 phenotype (linkage disequilibrium with HLA - DR3) towards the production of anti-insulin antibodies and hyperimmune clinical manifestations, such as allergy. Reliable conclusions are not possible between low and high responders for the other phenotypes (HLA - B7, B8, B15) commonly implicated. HLA-B12 was noted in 3 of 5 patients with allergy, in 2 cases associated with B8.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[HLA typing and insulin antibody production in insulin-dependent diabetics]. 644 4

A group of patients with Type 1 (insulin-dependent) diabetes mellitus was investigated for HLA-A, B and DR antigens as well as C4 and factor B polymorphism. A significant excess of DR3/DR4 heterozygotes was observed (27% versus 17% by Hardy-Weinberg expectation). The factor B allele BfF1 was present in 13% of patients with Type 1 diabetes (gene frequency of 0.08 versus 0.01 in control subjects). A rare C4 B allele, C4 B2.9, was found in 18% of patients with Type 1 diabetes (n = 63) compared with 1.1% of control subjects (n = 176). Total C4 deficiency at the C4 A locus (C4 AQ0,0) was present in 10% of patients with Type 1 diabetes compared with 0% of control subjects. Examination of HLA, C4 and Bf phenotypes in patients with Type 1 diabetes suggested that three high risk supratypes, HLA-A1 B8 BfS C4 AQ0 C4 B1 DR3; HLA-B18 BfF1 C4 A3 C4 BQ0 DR3; HLA-A2 CW3 BW62 BfS C4 A3 C4 B2.9 DR4 are markers for susceptibility alleles.
 ...
PMID:HLA and complement allotypes in Type 1 (insulin-dependent) diabetes. 657 86

The HLA antigen combination A9, Bw16 has been found to be associated with Type 1 (insulin-dependent) diabetes characterized by some special features in Northern Finland. This antigen combination has now been associated with a 'new' DR4-associated D antigen, provisionally called 'JA' or 'SN'. This 'new' D specificity was also associated with HLA-B18. Although the combination, Dw3/DJA, was common in Type 1 diabetic patients, the frequency of the combination Dw4/DJA was decreased compared with the expected value. This supports the hypothesis of two different risk factors associated with DR3 and DR4.
 ...
PMID:A 'new' DR4 associated D specificity 'JA' in type 1 (insulin-dependent) diabetes: A9, Bw16, DJA, DR4 haplotype. 659 18

One hundred and thirty-three insulin-dependent diabetic (IDD) patients were genotyped for HLA-A, B, C, DR and 123 of them for Bf. The study shows a relationship between these genes and the age of onset of diabetes and emphasizes the possible heterogeneity of the disease. When patients under the age of 0 years at the onset of the disease were compared with those aged 11 to 29 years, a significant excess of HLA-B18 (41% versus 15%, p less than 0.001) and BfF1 (40% versus 21%, P less than 0.05) was observed. The haplotype B18, BfF1 was also more frequent in the first group of patients (haplotype frequency 18% versus 6%, p less than 0.02). The frequency of the whole haplotype Cw5, B18, BfF1, DR3 and of its segment BfF1, DR3, and the strength of the gametic associations between these alleles were much higher in IDD patients than in non-diabetic controls, irrespective of the age of onset of their diabetes. The association between early age of onset of IDD and the B18, BfF1 haplotype independently of DR3 (no association between age and DR3) suggests that a factor influencing the onset of the disease in young children could be under the control of (1) gene (s) in linkage disequilibrium with B18 and/or BfF1.
 ...
PMID:Age--related heterogeneity of insulin-dependent diabetes mellitus. 660 51

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.
 ...
PMID:Extended major histocompatibility complex haplotypes in type I diabetes mellitus. 674 3

The HLA and the Bf systems were studied as part of a family investigation carried out in Portugal. In four generations the rare phenotype BfF1 could be determined four times and the BfF1S phenotype six times, HLA-B18 being simultaneously positive in all cases. Since the frequencies of the individual factors F1 and B18 do not differ essentially from those obtained in Central Europe and no inbreeding situation was present, the high-grade linkage disequilibrium between F1 and B18 may also be presumed for the Portuguese population. Neither among the F1/B18 homozygous nor among the heterozygous subjects could one discern any morbid state (e.g., insulin-dependent diabetes mellitus) from which an association with the F1/B18 haplotype could be deduced. Finally, the rarity of Bf factors, such as F1 and S0.7, is discussed from the standpoint of selection vs. mutation.
 ...
PMID:[High association between properdin factors BfF1 and HLA-B 18 in a Portuguese family (author's transl)]. 691 88

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.
Diabetes 1980 Jun
PMID:Properdin factor B(Bf) allele BfF1 specifies an HLA-B18 diabetogenic haplotype. 692 67

Five hundred and ninety-nine patients with insulin-dependent (Type 1) diabetes mellitus were typed for Bf (factor B) polymorphism, and 318 of them for HLA-A, B and C antigens. Bf and HLA antigen frequencies were compared with those in 536 normal controls. A significant positive association between Type 1 diabetes and the rare factor B variant BfF1 was found (p less than 10(-3)), but this was present only in patients aged under 16 years at onset of the disease (p less than 0.005). There was a strongly positive linkage disequilibrium between BfF1 and HLA-B18 in the diabetic patients. This, too was especially pronounced in the juvenile onset cases, in whom it was significantly stronger than in controls (p less than 10(-3)). The known positive associations between Type 1 diabetes and HLA-B8, -B15 and -Cw3 were confirmed.
 ...
PMID:Age-related association of insulin-dependent diabetes mellitus with BfF1 and the HLA-B18, BfF1 haplotype. 702 28

To determine the association of histocompatability antigens (HLA) with insulin-dependent diabetes (IDD) in Mexican-Americans, we determined HLA-A, -B, and -C specificities in 112 unrelated patients and 332 controls, and HLA-DR specificities in 85 patients and 209 controls. We also studied immunoglobulin G (IgG) insulin antibody formation in 56 Mexican-Americans with IDD, and the relationship between antibody formation and HLA-DR antigens. IDD patients have a significant increase in HLA-DR4 compared to the control population (chi 2 = 14.75; corrected P less than 0.0001). HLA-DR2 was not detected in any patient with IDD. A significant association between HLA-Aw30 and HLA-B18 was found in IDD patients (chi 2 = 9.39; P less than 0.05) as compared to controls. IgG insulin antibody formation was significantly increased in HLA-DR3- and -DR4-negative patients compared to that in patients positive for both antigens (P less than 0.05). These findings support previous observations in caucasians and black Americans indicating that HLA-DR specificities are associated with IDD and may play a role in determining its mode of inheritance, and perhaps its pathogenesis, independent of ethnic differences. HLA-DR immune-associated antigens are also of importance in determining IgG insulin antibody formation.
 ...
PMID:Histocompatability antigens and immunoglobulin G insulin antibodies in Mexican-American insulin-dependent diabetic patients. 703 84


<< Previous 1 2 3 Next >>