Extended major histocompatibility complex haplotypes in type I diabetes mellitus

Donald Douglas Raum, Z. Awdeh, E. Yunis

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Abstract

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 < 0.1. 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.

Original languageEnglish (US)
Pages (from-to)449-454
Number of pages6
JournalJournal of Clinical Investigation
Volume74
Issue number2
StatePublished - 1984
Externally publishedYes

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Major Histocompatibility Complex
Type 1 Diabetes Mellitus
Haplotypes
HLA-DR4 Antigen
HLA-DR3 Antigen
HLA-B18 Antigen
HLA-B8 Antigen
Alleles
HLA-B15 Antigen
Chromosomes
HLA-DR2 Antigen
HLA-B7 Antigen
HLA-B Antigens
Disease Susceptibility
HLA-DR Antigens
Ethnic Groups
Genes
Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Extended major histocompatibility complex haplotypes in type I diabetes mellitus. / Raum, Donald Douglas; Awdeh, Z.; Yunis, E.

In: Journal of Clinical Investigation, Vol. 74, No. 2, 1984, p. 449-454.

Research output: Contribution to journalArticle

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