Genetics of Insulin-Dependent Diabetes Mellitus.

Ikegami, Hiroshi; Ogihara, Toshio

doi:10.1507/endocrj.43.605

Cited by 68 publications

(62 citation statements)

References 23 publications

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“…When compared with susceptible haplotypes, resistant HLA haplotype DR2 has a strong protective effect on the development of classical autoimmune Type 1 diabetes, so subjects with the diabetes-resistant haplotype rarely develop diabetes [23]. In the present study, diabetes-resistant alleles were frequently found in fulminant Type 1 diabetic patients (36.4%).…”

Section: Discussionsupporting

confidence: 46%

T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes

et al. 2004

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Aims/hypothesis. Fulminant Type 1 diabetes is a novel subtype of Type 1 diabetes that involves the abrupt onset of insulin-deficient hyperglycaemia. This subtype appears to be non-autoimmune because of the absence of diabetes-related autoantibodies in the serum, and of insulitis in pancreatic biopsy specimens. The pathogenesis of the disease is still unknown. In this study, we investigated whether T cell autoimmune responses are involved in fulminant Type 1 diabetes. Methods. Cellular immune responses to beta cell autoantigens were studied by enzyme-linked immunospot (ELISPOT) assay in 13 fulminant Type 1 diabetic patients and 49 autoantibody-positive autoimmune Type 1 diabetic patients. Results were compared with those of 18 Type 2 diabetic patients, six secondary diabetic patients (diabetes due to chronic pancreatitis) and 35 healthy controls. Results. Nine of 13 (69.2%) GAD-reactive Th1 cells, and three of 12 (25%) insulin-B9-23-reactive Th1 cells were identified in fulminant Type 1 diabetic patients by ELISPOT, as in autoantibody-positive Type 1 diabetic patients. Four fulminant Type 1 diabetic patients possessed the highly diabetes-resistant allele DR2, three of whom had GAD-reactive Th1 cells in the periphery. Conclusions/interpretation. Peripheral immune reaction was observed in 69.2% of fulminant Type 1 diabetic patients, indicating that autoreactive T cells might contribute, at least in part, to the development of fulminant Type 1 diabetes.

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Section: Discussionsupporting

confidence: 46%

T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes

et al. 2004

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“…Because the Japanese are a genetically homogeneous population [16,17], geo-ethnic variation in type 1 diabetes risk probably reflects differences in the frequencies of modifier genes (susceptibility or protective) or environmental factors (causative or protective) or some combination thereof [18,19]. It was reported that monozygotic twins and first degree relatives of patients with type 1 diabetes in Japan had a similar risk of diabetes to twins and relatives of patients in the United States [5], suggesting that most of the between-country variation in diabetes risk might relate to genetic differences rather than environmental factors.…”

Section: Epidemiology Of Type 1 Diabetes In Japanmentioning

confidence: 99%

“…Thus λs, the ratio of the risk for siblings of type 1 diabetic patients and the risk in the general population, is approximately 15 in Caucasoid populations [4]. In contrast, λs for type 1 diabetes in Japan is estimated to be more than 250 (3.8 vs 0.014%), much higher than that in Caucasoid populations [5]. The reason why the incidence rate of type 1 diabetes is so low in Asian countries, including Japan, is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Type 1 diabetes in Japan

2006

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“…Several additional loci have recently been mapped to the human genome by whole genome scanning with random markers [4±8] and/or a candidate gene approach [9±14]. Most reports, however, are based on data in Caucasian populations, and it is yet to be determined whether loci mapped in one population universally contribute to IDDM susceptibility in other populations.The Japanese population is unique in studies on the genetics of IDDM not only because they are genetically distinct from Caucasian populations, but also because the incidence of IDDM is very low in this population [15]. We have previously reported that two IDDM loci, IDDM1 in HLA region [15,16] and IDDM2 in the insulin gene (INS) region [17], both of which were identified by the candidate gene approach, contribute to IDDM susceptibility in Japanese in the same way as in Caucasians.…”

mentioning

confidence: 99%

“…The Japanese population is unique in studies on the genetics of IDDM not only because they are genetically distinct from Caucasian populations, but also because the incidence of IDDM is very low in this population [15]. We have previously reported that two IDDM loci, IDDM1 in HLA region [15,16] and IDDM2 in the insulin gene (INS) region [17], both of which were identified by the candidate gene approach, contribute to IDDM susceptibility in Japanese in the same way as in Caucasians.…”

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confidence: 99%

Association of distal chromosome 2q with IDDM in Japanese subjects

Ikegami

Kawaguchi

et al. 1998

Diabetologia

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Insulin-dependent diabetes mellitus (IDDM) is caused by autoimmune destruction of insulin-producing beta cells of the pancreas in genetically susceptible individuals [1]. Inheritance of IDDM is polygenic with a major locus (IDDM1) in the major histocompatibility complex (MHC) [2,3]. Several additional loci have recently been mapped to the human genome by whole genome scanning with random markers [4±8] and/or a candidate gene approach [9±14]. Most reports, however, are based on data in Caucasian populations, and it is yet to be determined whether loci mapped in one population universally contribute to IDDM susceptibility in other populations.The Japanese population is unique in studies on the genetics of IDDM not only because they are genetically distinct from Caucasian populations, but also because the incidence of IDDM is very low in this population [15]. We have previously reported that two IDDM loci, IDDM1 in HLA region [15,16] and IDDM2 in the insulin gene (INS) region [17], both of which were identified by the candidate gene approach, contribute to IDDM susceptibility in Japanese in the same way as in Caucasians. The contribution of other loci, however, to IDDM susceptibility in Japanese is largely unknown due to their low incidence and, as a consequence, the limited number of multiplex families with IDDM. Diabetologia (1998) Summary An insulin-dependent diabetes mellitus (IDDM)-susceptibility gene (IDDM13) has recently been mapped to a region of distal chromosome 2q, which is syntenic to the region of mouse chromosome 1 containing a murine susceptibility gene for IDDM, Idd5. To determine the contribution of this region to IDDM disease susceptibility further and to narrow the region for positional cloning of susceptibility genes, we have studied the association of distal chromosome 2q with IDDM in the genetically distinct Japanese population. A 137 mobility unit (mu) allele at D2S137 locus was significantly associated with IDDM (odds ratio 1.92, p = 0.0016). Other markers, D2S301 and D2S143, located in the same region were not associated with IDDM, indicating that IDDM13 is in linkage disequilibrium with D2S137, but not with D2S301 or D2S143. The association of D2S137 with IDDM was observed in patients lacking one of two high risk HLA alleles, DQB1*0303 and DQB1*0401, but not in patients with either of these alleles. The frequency of high risk HLA alleles was significantly lower in patients with the susceptible allele at D2S137, suggesting that IDDM13 contributes to IDDM susceptibility in subjects without high risk genotypes at IDDM1. Demonstration of allelic association of D2S137 with IDDM localizes IDDM13 in the close vicinity (< 2 centiMorgans) of D2S137, greatly facilitating fine structure mapping and positional cloning of IDDM13. [Diabetologia (1998) 41: 228±232]

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Genetics of Insulin-Dependent Diabetes Mellitus.

Cited by 68 publications

References 23 publications

T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes

T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes

Type 1 diabetes in Japan

Association of distal chromosome 2q with IDDM in Japanese subjects

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