Immunogenetic heterogeneity in Type 1 (insulin-dependent) diabetes among Japanese ? HLA antigens and organ-specific autoantibodies

Kida, Kaichi; Mimura, Goro; Kobayashi, Tetsuro; Nakamura, Ko; Sonoda, Shunro; Inouye, Hiroo; Tsuji, Kimiyoshi

doi:10.1007/bf00265401

Cited by 46 publications

(17 citation statements)

References 31 publications

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“…This observation confirmed previous reports in Japanese patients with IDDM [4,5,8]. In the present study we further found that the frequency of DQw3.2 was higher in IDDM than in control subjects.…”

Section: Discussionsupporting

confidence: 94%

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Heterogeneity of Non-Insulin-Dependent Diabetes Mellitus in HLA Types and Clinical Features: Comparison with Insulin-Dependent Diabetes Mellitus.

et al. 1991

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Abstract. We determined HLA types in 110 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and studied the relationship between the HLA phenotypes and clinical features. Sixty-nine patients with insulin-dependent diabetes mellitus (IDDM) and 100 healthy blood donors served as controls. Concerning HLA DR and DQ loci, frequencies of DR4, DRw9 and DQw3.2 were higher, and those of DR2, DRw8, DRw 11, DRw12 and DQw1 were lower in patients with IDDM compared than in healthy controls. There were no differences between NIDDM and normal controls in the frequency of a particular HLA DR antigen except for a decreased frequency in DRw 11 in the former. The frequency of DQw3.2 antigen in NIDDM was intermediate between IDDM and normal controls. There were some differences between DQw3.2-positive and -negative NIDDM patients in clinical features. Those who showed low C-peptide responses during oral glucose tolerance test were more frequently found among DQw3.2-positive NIDDM patients. These results suggest that Type 1 diabetes mellitus may have a mild clinical course and is found among the Japanese NIDDM population.

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Section: Discussionsupporting

confidence: 94%

“…IT IS NOW well established that insulin dependent diabetes mellitus (IDDM) (Type 1 diabetes) is associated with particular HLA antigen types; it has positive associations with DR3 and DR4 in Caucasians [1][2][3] and with DR4 and DRw9 in Japanese [2,4,5]. On the other hand, noninsulin-dependent diabetes mellitus (NIDDM) has no association with HLA antigens.…”

mentioning

confidence: 99%

Heterogeneity of Non-Insulin-Dependent Diabetes Mellitus in HLA Types and Clinical Features: Comparison with Insulin-Dependent Diabetes Mellitus.

et al. 1991

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“…A total of 80 patients (age Ͻ18 years) in the CO group were recruited from the Ehime prefecture, some of whose clinical and immunogenetic characteristics have been already reported by Kida and colleagues (27,28). All these CO patients were considered to be acute-onset types based on the abovementioned criteria.…”

Section: Methodsmentioning

confidence: 99%

Differences in the Contribution of HLA-DR and -DQ Haplotypes to Susceptibility to Adult- and Childhood-Onset Type 1 Diabetes in Japanese Patients

et al. 2004

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To clarify heterogeneity in Japanese adult-onset type 1 diabetes, we analyzed the HLA-DR and -DQ haplotypes, depending on the clinical phenotype, and compared them with those in childhood-onset type 1 diabetes (CO). The patients in a previously reported Ehime Study were divided into subgroups by the mode of onset of diabetes: 68 acute-onset type 1 diabetic patients (AO) and 28 slowly progressive type 1 diabetic patients (SO). HLA haplotypes were compared with those of 80 CO patients and 190 control subjects. Two major susceptible HLA haplotypes in the Japanese, DRB1*0405-DQB1*0401 (DR4) and DRB1*0901-DQB1*0303 (DR9), were significantly increased in the AO and CO groups, but only DR9 was increased in the SO group. AO subjects had a higher frequency of DR9 than CO subjects. Accordingly, the DR9:DR4 frequency increased with increasing age of onset. Another susceptible haplotype, DRB1*0802-DQB1*0302 (DR8), was involved only in the CO group. Analysis of haplotype combinations revealed that DR4 and DR9 had significant dosage effects on the AO and CO groups (P < 0.0001), but only DR9 had such an effect in the SO group (P < 0.03). These results suggest differences in the contribution of HLA class II haplotypes to susceptibility of type 1 diabetes depending on the clinical phenotype and also indicate that HLA class II haplotypes may be associated with the onset age of type 1 diabetes. Diabetes 53: 2684 -2690, 2004 T ype 1 diabetes is the result of a destruction of pancreatic ␤-cells and leads to complete insulin deficiency (1,2). Although type 1 diabetes is frequently considered to be a childhood disease and is characterized by a rapid progression to insulin dependency, the clinical onset of type 1 diabetes is not confined to children. Epidemiological data suggest that 30 -50% of type 1 diabetic patients may develop clinical signs of diabetes after age 20 years (3,4). Moreover, there is increasing evidence to indicate that type 1 diabetes, especially when developed in adulthood, is clinically and immunologically heterogeneous. Insulin secretion abruptly ceases in fulminant type 1 diabetes (5), whereas pancreatic ␤-cell function can be preserved for over a decade in some patients, a condition that is referred to as slowly progressive insulin-dependent diabetes (6) or latent autoimmune diabetes in adults (LADA) (7). Compared with our extensive knowledge of the epidemiological, clinical, and genetic characteristics of childhood-onset type 1 diabetes, our understanding of adult-onset type 1 diabetes is incomplete.Susceptibility to type 1 diabetes is determined by both environmental and genetic factors. Although multiple genes have been implicated, HLA class II genes, especially the HLA-DR and -DQ genes, are most important and are estimated to account for ϳ50% of the susceptibility to the disease (8). These HLA associations vary depending on geographic and ethnic origin (9). It has been shown that Japanese type 1 diabetic patients have different HLA associations than Caucasian patients. In Caucasian populations, the DRB1*...

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“…A maioria dos estudos nessa área tem sido realizada em caucasianos europeus e norte-americanos (1,4,15,16). Outras populações estudadas tem sido as da África do Sul (17), Jamaica (18), Camarões (19) e Japão (20)(21)(22), apenas para citar alguns exemplos.…”

Section: Introductionunclassified

Distribuição e freqüência de alelos e haplotipos HLA em brasileiros com diabetes melito tipo 1

Alves

Meyer

Vieira

et al. 2006

Arq Bras Endocrinol Metab

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RESUMOA predisposição genética ao diabetes melito tipo 1 (DM1) é associada a múltiplos genes do sistema de histocompatibilidade humano (HLA) de classe II. Em caucasianos, os antígenos HLA-DR3 e -DR4 são associados à susceptibilidade e o -DR2, à proteção. No Brasil, um país constituído por grande miscigenação entre caucasianos europeus, índios nativos e negros africanos, a base genética do DM1 tem sido pouco estudada. O objetivo desse trabalho foi apresentar uma revisão crítica dos artigos indexados nos bancos de dados MEDLINE e LILACS-BIREME sobre a associação do HLA com DM1 em brasileiros. Todos os oito estudos encontrados foram realizados no sudeste do país. A susceptibilidade imunogenética para o DM1 em brasileiros foi associada com os alelos HLA-DRB1*03, -DRB1*04, -DQB1*0201, -DQB1*0302 e a proteção com os alelos -DQB1*0602 e -DQB1*0301 e os antígenos -DR2 e -DR7. Por ser o Brasil constituído por grande miscigenação, não se pode extrapolar para todo o país estudos realizados em apenas uma região. Faz-se necessário pesquisar populações de várias regiões, analisando sua diversidade alélica para identificar novas associações ou reforçar aquelas já existentes. Esse conhecimento contribuirá para futuras intervenções profiláticas e terapêuticas nos grupos de brasileiros com maior risco de desenvolver DM1. The genetic predisposition to type 1 diabetes (DM1) is associated with genes of the human leukocyte antigen (HLA) system, specially the HLA-DR and -DQ. In Caucasians, the HLA-DR3 and -DR4 antigens are associated with susceptibility and the -DR2, with protection. In Brazil, a country with a large miscegenation of Europeans Caucasians, Native Amerindians and African Blacks, the genetic basis of DM1 has not been adequately studied. The aim of this paper is to present a critical review of articles indexed in the MEDLINE and LILACS-BIREME data basis about the association of HLA with DM1 in Brazilians. Eight papers, all of them from the Southeast region, were found. Immunogenetic susceptibility to DM1 in Brazilians was associated with HLA-DRB1*03, -DRB*04, -DQB1*0201, -DQB1*0302 alleles, and protection against DM1 was associated with HLA-DQB1*0602, -DQB1*0301 alleles and -DR2 and -DR7 antigens. Since the Brazilian population is not racially homogeneous, it is not possible to extrapolate studies from a single region to the remaining of the country. It is necessary to study populations from different regions to identify new associations or to strengthen associations with the ones already identified. This knowledge will con-

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Immunogenetic heterogeneity in Type 1 (insulin-dependent) diabetes among Japanese ? HLA antigens and organ-specific autoantibodies

Cited by 46 publications

References 31 publications

Heterogeneity of Non-Insulin-Dependent Diabetes Mellitus in HLA Types and Clinical Features: Comparison with Insulin-Dependent Diabetes Mellitus.

Heterogeneity of Non-Insulin-Dependent Diabetes Mellitus in HLA Types and Clinical Features: Comparison with Insulin-Dependent Diabetes Mellitus.

Differences in the Contribution of HLA-DR and -DQ Haplotypes to Susceptibility to Adult- and Childhood-Onset Type 1 Diabetes in Japanese Patients

Distribuição e freqüência de alelos e haplotipos HLA em brasileiros com diabetes melito tipo 1

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