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HLA and GM in insulin-dependent diabetes in the Netherlands: report on a combined multiplex family and population study.
Hum Immunol. 1984 May; 10(1):5-21.HI

Abstract

This report deals with the genetic factors involved in insulin-dependent diabetes mellitus (IDD) in The Netherlands. Twenty-two Dutch multiplex families with IDD were typed for HLA-A, -B, -C, and -DR antigens, for BF, C2, C4, and GLO polymorphisms, as well as for GM allotypes of immunoglobulins. In addition, 53 unrelated IDD children and 31 unrelated patients with adult onset IDD were typed for HLA-A, -B, -C, and -DR antigens. A significant heterogeneity for the frequency of HLA-DR4 related to age of onset was observed. A significant deviation of the Hardy-Weinberg equilibrium was observed for the HLA-DR locus with an excess in patients of heterozygotes HLA-DR3, -DR4.HLA-B8, and HLA-B15 were not only secondary associated, but constituted with HLA-DR3 and -DR4, respectively, a haplotype in association with IDD. Nonrandom segregation of HLA-haplotypes was observed in multiplex families exemplified by an excess of HLA-identical affected sibpairs . Cross- overs between HLA-DR and GLO identified the HLA-DR segment as mainly involved in the association with IDD. Three diabetic haplotypes were confirmed to occur frequently among affected sibs: (a) A1, B8, BFS, C2.1, C4AQO , C4B1 ,DR3, GLO2 ; (b) Aw30, Cw5 ,B18,BFF1,C2.1, C4A3 , C4BQO ,DR3, GLO2 ; (c) A2,Cw3, B15,BFS, C2.1, C4A3 , C4B3 , DR4,GLO1. The segregation of GM allotypes to affected sibpairs was not significantly different from random segregation. The main conclusions from this study are that significant heterogeneity for age of onset exists and that the data are not compatible with simple genetic models including dominant, recessive, and intermediate models of inheritance. The data do require more complex models, involving two different HLA-linked (sets of) susceptibility genes.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

6586708

Citation

de Jongh, B M., et al. "HLA and GM in Insulin-dependent Diabetes in the Netherlands: Report On a Combined Multiplex Family and Population Study." Human Immunology, vol. 10, no. 1, 1984, pp. 5-21.
de Jongh BM, Bruining GJ, Schreuder GM, et al. HLA and GM in insulin-dependent diabetes in the Netherlands: report on a combined multiplex family and population study. Hum Immunol. 1984;10(1):5-21.
de Jongh, B. M., Bruining, G. J., Schreuder, G. M., Schuurman, R. K., Radder, J. K., van Loghem, E., Meera Khan, P., Hauptmann, G., & van Rood, J. J. (1984). HLA and GM in insulin-dependent diabetes in the Netherlands: report on a combined multiplex family and population study. Human Immunology, 10(1), 5-21.
de Jongh BM, et al. HLA and GM in Insulin-dependent Diabetes in the Netherlands: Report On a Combined Multiplex Family and Population Study. Hum Immunol. 1984;10(1):5-21. PubMed PMID: 6586708.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HLA and GM in insulin-dependent diabetes in the Netherlands: report on a combined multiplex family and population study. AU - de Jongh,B M, AU - Bruining,G J, AU - Schreuder,G M, AU - Schuurman,R K, AU - Radder,J K, AU - van Loghem,E, AU - Meera Khan,P, AU - Hauptmann,G, AU - van Rood,J J, PY - 1984/5/1/pubmed PY - 1984/5/1/medline PY - 1984/5/1/entrez SP - 5 EP - 21 JF - Human immunology JO - Hum Immunol VL - 10 IS - 1 N2 - This report deals with the genetic factors involved in insulin-dependent diabetes mellitus (IDD) in The Netherlands. Twenty-two Dutch multiplex families with IDD were typed for HLA-A, -B, -C, and -DR antigens, for BF, C2, C4, and GLO polymorphisms, as well as for GM allotypes of immunoglobulins. In addition, 53 unrelated IDD children and 31 unrelated patients with adult onset IDD were typed for HLA-A, -B, -C, and -DR antigens. A significant heterogeneity for the frequency of HLA-DR4 related to age of onset was observed. A significant deviation of the Hardy-Weinberg equilibrium was observed for the HLA-DR locus with an excess in patients of heterozygotes HLA-DR3, -DR4.HLA-B8, and HLA-B15 were not only secondary associated, but constituted with HLA-DR3 and -DR4, respectively, a haplotype in association with IDD. Nonrandom segregation of HLA-haplotypes was observed in multiplex families exemplified by an excess of HLA-identical affected sibpairs . Cross- overs between HLA-DR and GLO identified the HLA-DR segment as mainly involved in the association with IDD. Three diabetic haplotypes were confirmed to occur frequently among affected sibs: (a) A1, B8, BFS, C2.1, C4AQO , C4B1 ,DR3, GLO2 ; (b) Aw30, Cw5 ,B18,BFF1,C2.1, C4A3 , C4BQO ,DR3, GLO2 ; (c) A2,Cw3, B15,BFS, C2.1, C4A3 , C4B3 , DR4,GLO1. The segregation of GM allotypes to affected sibpairs was not significantly different from random segregation. The main conclusions from this study are that significant heterogeneity for age of onset exists and that the data are not compatible with simple genetic models including dominant, recessive, and intermediate models of inheritance. The data do require more complex models, involving two different HLA-linked (sets of) susceptibility genes. SN - 0198-8859 UR - https://www.unboundmedicine.com/medline/citation/6586708/HLA_and_GM_in_insulin_dependent_diabetes_in_the_Netherlands:_report_on_a_combined_multiplex_family_and_population_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0198-8859(84)90082-X DB - PRIME DP - Unbound Medicine ER -