MLC Typing in Juvenile Diabetes Mellitus and Idiopathic Addison's Disease

Thomsen, Mögens; Platz, P.; Andersen, O. Ortved; Christy, M.; Lyngsøe, J.; Nerup, J.; Rasmussen, Karsten; Ryder, Lars P.; Nielsen, Line; Svejgaard, A.

doi:10.1111/j.1600-065x.1975.tb01555.x

Cited by 126 publications

(95 citation statements)

References 20 publications

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“…Evidence from diabetic twin studies has hinited at important environmental factors in the pathogeniesis of at least some cases of JIDD (2), and findings of associations betwteen histocompatibilitv (HLA) antigens and JIDD have strengthened the genetic theory of the disease. Associations of HLA anitigens B8 (3)(4)(5), BW15 (3,(4)(5)(6), CW3 (7), and DW3 (8) have been described with JIDD, and it has been postulated that a gene (or genes) linked to and in disequilibrium with loci B and D of the HLA complex is important in the pathogenesis of this form of diabetes (4). Similar findings have not been found with typical adultonset, insulin-independent diabetes, confirming the belief that these two forms of diabetes are genetically different.…”

Section: Introductionsupporting

confidence: 69%

The Histocompatibility System in Juvenile, Insulin-Dependent Diabetic Multiplex Kindreds

Barbosa¹,

King²,

Noreen³

et al. 1977

J. Clin. Invest.

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A B S T R A C T We have histocompatibility (HLA) genotyped 24 families with two or more juvenile, insulin-dependent, ketosis-prone diabetic siblings. This criterion for family selection was used to obtain a homogeneous form of diabetes within a sibship, because diabetes appears to be a genetically heterogeneous disease. 58 diabetic and 53 nondiabetic sibs and 40 parents were studied. 55% of the diabetic pairs were concordant for both HLA haplotypes (expected 25%), 40% were concordant for one haplotype (expected 50%), and 5% were discordant for both haplotypes (expected 25%). These values are significantly different from the expected values (P < 0.001). On the other hand, the inheritance of haplotypes among the nondiabetic sibs in these families was not significantly different from the expected mendelian segregation.When comparing 20 pairs of HLA identical (sharing two haplotvpes) with 15 pairs of haploidentical (sharing one haplotvpe) diabetic sibs for the intrapair difference in age of oniset of disease, we found that the HLA idenitical sibs were significantly more concordanit for age of onset (3.9 yr differenice) than the haploidentical (7.3 yr difference) (P < 0.05). The same type of analyrsis for the difference in seasonal incidence in months revealed that the HLA identical sibs were more concordant (1.8 mo difference) than the haploidentical sibs (3.2 mo difference) (P < 0.025). Furthermore, the HLA identical diabetic sibs were more likely to develop diabetes in the winter months (78%) than the haploidentical diabetic sibs (21%).No particular HLA haplotype or antigen seemed to be associated with any particular clinical feature.

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Section: Introductionsupporting

confidence: 69%

The Histocompatibility System in Juvenile, Insulin-Dependent Diabetic Multiplex Kindreds

Barbosa¹,

King²,

Noreen³

et al. 1977

J. Clin. Invest.

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“…In the 1970s, association and affected-sib pair linkage studies established the role of HLA genes in T1D predisposition (the HLA locus contribution to disease is referred to as IDDM1). [12][13][14] HLA studies also demonstrated that T1D and type 2 (non insulin-dependent) diabetes mellitus (T2D) were distinct disease entities, since T2D generally does not show an association with HLA, although certain subsets may demonstrate some association. 15 The variability in rates of T1D disease concordance in siblings who share two, one or zero parental HLA haplotypes in addition to the different concordance rates in monozygotic vs dizygotic twins, the risk in relatives, and the population prevalence implicates the existence of additional non-HLA genetic factors.…”

Section: Genetics Of T1dmentioning

confidence: 99%

Genetics of type 1 diabetes mellitus

2002

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“…Human leukocyte antigen (HLA) association of the disease with the common 'autoimmune' HLA-DR3 haplotype has been known for decades (6) and some studies have also found an increased frequency of HLA-DR4 among patients (7,8). An association with specific HLA-DR4-positive haplotype, HLA-DQB1*0302-DRB1*0404, was described among Addison's disease patients and diabetic children positive for 21-hydroxylase autoantibodies (9).…”

Section: Introductionmentioning

confidence: 99%

Analysis of extended human leukocyte antigen haplotype association with Addison's disease in three populations

Gombos¹,

Hermann²,

Kiviniemi³

et al. 2007

European Journal of Endocrinology

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Objective: Addison's disease is an organ-specific autoimmune disorder with a polygenic background. The aim of the study was to identify non-class II human leukocyte antigen (HLA) susceptibility genes for Addison's disease. Design and methods: Addison's disease patients from three European populations were analysed for selected HLA-DR-DQ alleles and for 11 microsatellite markers covering w4 Mb over the HLA region. Subjects were 69 patients with Addison's disease from Estonia (24), Finland (14) and Russia (31). Consecutively recruited healthy newborns from the same geographical regions were used as controls (269 Estonian, 1000 Finnish and 413 Russian). Association measures for HLA-DRB1, DQB1, DQA1 and 11 microsatellites between D6S273 and D6S2223 were taken. A low-resolution full-house typing was used for HLA class II genes, while microsatellite markers were studied using fluorescence-based DNA fragment sizing technology. Results: We confirmed that the HLA-DR3-DQ2 and the DQB1*0302-DRB1*0404 haplotypes confer disease susceptibility. In Russian patients, we also found an increase of DRB1*0403 allele, combined with DQB1*0305 allele in three out of six cases (P!0.0001). Analysis of 11 microsatellite markers including STR MICA confirmed the strong linkage in DR3-DQ2 haplotypes but DRB1*0404-DQB1*0302 haplotypes were diverse. MICA5.1 allele was found in 22 out of 24 Estonian patients, but results from Finnish and Russian patients did not support its independent role in disease susceptibility. Conclusion: HLA-DRB1*0403 was identified as a novel susceptibility allele for Addison's disease. Additionally, we found no evidence of a non-class II HLA disease susceptibility locus; however, the HLA-DR3-DQ2 haplotype appeared more conserved in patient groups with high DR-DQ2 frequencies.

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MLC Typing in Juvenile Diabetes Mellitus and Idiopathic Addison's Disease

Cited by 126 publications

References 20 publications

The Histocompatibility System in Juvenile, Insulin-Dependent Diabetic Multiplex Kindreds

The Histocompatibility System in Juvenile, Insulin-Dependent Diabetic Multiplex Kindreds

Genetics of type 1 diabetes mellitus

Analysis of extended human leukocyte antigen haplotype association with Addison's disease in three populations

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