Biomaterial Database

HLA haplotype sharing by siblings with rheumatoid arthritis: evidence for genetic heterogeneity. 1986

D M Grennan, and P A Sanders, and P A Dyer, and R Harris

HLA haplotype sharing was studied in 35 sibships in which there were two or more members with rheumatoid arthritis (RA). Haplotype sharing RA siblings was random in 15 sibships which included members with clinical or immunological features of autoimmune thyroid disease. In the remaining 20 'non-thyroid' sibships the frequencies of RA siblings sharing 0, 1, or 2 haplotypes were 0.04, 0.48, and 0.48 respectively (p = 0.006). 67% of RA probands in the 'thyroid' families and 90% in the other families were HLA-DR4 positive. It is suggested that there is genetic heterogeneity in the pathogenesis of RA with at least two independent genes within the major histocompatibility complex (MHC) predisposing to RA. One gene is in linkage disequilibrium with HLA-DR4, while results of comparison of DR antigen frequencies in DR4 negative RA and control groups suggest that the other is in linkage disequilibrium with HLA-DR1 and 3. In the thyroid disease families both genes are frequently present and as either may predispose to arthritis, HLA haplotype sharing is random. The frequencies of HLA haplotype sharing in the 'non-thyroid' families suggest that there is a dominant susceptibility gene in linkage disequilibrium with HLA-DR4, whose frequency is 5% and penetrance about 20%.

UI	MeSH Term	Description	Entries
D005787	Gene Frequency	The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.	Allele Frequency,Genetic Equilibrium,Equilibrium, Genetic,Allele Frequencies,Frequencies, Allele,Frequencies, Gene,Frequency, Allele,Frequency, Gene,Gene Frequencies
D005799	Genes, Dominant	Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.	Conditions, Dominant Genetic,Dominant Genetic Conditions,Genetic Conditions, Dominant,Condition, Dominant Genetic,Dominant Gene,Dominant Genes,Dominant Genetic Condition,Gene, Dominant,Genetic Condition, Dominant
D006238	Haploidy	The chromosomal constitution of cells, in which each type of CHROMOSOME is represented once. Symbol: N.	Haploid,Haploid Cell,Cell, Haploid,Cells, Haploid,Haploid Cells,Haploidies,Haploids
D006680	HLA Antigens	Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.	Human Leukocyte Antigen,Human Leukocyte Antigens,Leukocyte Antigens,HL-A Antigens,Antigen, Human Leukocyte,Antigens, HL-A,Antigens, HLA,Antigens, Human Leukocyte,Antigens, Leukocyte,HL A Antigens,Leukocyte Antigen, Human,Leukocyte Antigens, Human
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000949	Histocompatibility Antigens Class II	Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.	Antigens, Immune Response,Class II Antigens,Class II Histocompatibility Antigen,Class II Major Histocompatibility Antigen,Ia Antigens,Ia-Like Antigen,Ia-Like Antigens,Immune Response Antigens,Immune-Associated Antigens,Immune-Response-Associated Antigens,MHC Class II Molecule,MHC II Peptide,Class II Antigen,Class II Histocompatibility Antigens,Class II MHC Proteins,Class II Major Histocompatibility Antigens,Class II Major Histocompatibility Molecules,I-A Antigen,I-A-Antigen,IA Antigen,MHC Class II Molecules,MHC II Peptides,MHC-II Molecules,Antigen, Class II,Antigen, I-A,Antigen, IA,Antigen, Ia-Like,Antigens, Class II,Antigens, Ia,Antigens, Ia-Like,Antigens, Immune-Associated,Antigens, Immune-Response-Associated,I A Antigen,II Peptide, MHC,Ia Like Antigen,Ia Like Antigens,Immune Associated Antigens,Immune Response Associated Antigens,MHC II Molecules,Molecules, MHC-II,Peptide, MHC II,Peptides, MHC II
D001172	Arthritis, Rheumatoid	A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.	Rheumatoid Arthritis
D001327	Autoimmune Diseases	Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.	Autoimmune Disease,Disease, Autoimmune,Diseases, Autoimmune
D013959	Thyroid Diseases	Pathological processes involving the THYROID GLAND.	Disease, Thyroid,Diseases, Thyroid,Thyroid Disease
D015804	HLA-DR4 Antigen	An HLA-DR antigen which is associated with HLA-DRB1 CHAINS encoded by DRB1*04 alleles.	HLA-DR4,Antigen, HLA-DR4,HLA DR4 Antigen