Biomaterial Database

The molecular basis for HLA class II associations with rheumatoid arthritis. 1987

G T Nepom, and J A Hansen, and B S Nepom

The association of HLA-DR4 with rheumatoid arthritis strongly implicates genes of the major histocompatibility complex (MHC) as contributing to disease susceptibility. Molecular analysis of MHC genes expressed on haplotypes in association with HLA-DR4 reveals that at least six different alleles of the DR beta 1 locus and at least three different alleles of the DQ beta locus occur on different DR4+ haplotypes. Some of these allelic differences are quite substantial, and others are rather subtle, involving as few as two amino acids. The analysis of individual DR and DQ alleles in rheumatoid arthritis identifies some DR4+ genes strongly associated with disease susceptibility and some DR4+ genes which are not. The Dw4(DR4) and Dw14(DR4) DR beta 1 genes appear to represent specific alleles which confer disease risk in RA; other DR beta 1 genes, such as Dw10(DR4), may represent DR beta genes altered during evolution which have lost their contribution to RA susceptibility. DQ beta 3.1(DQw3) and DQ beta 3.2(DQw3) DQ beta genes, which are present on DR4+ haplotypes, represent discrete variable alleles not directly implicated in RA, but which account for HLA-DR4 associations with other diseases, such as the association of DQ beta 3.2(DQw3) with Type I diabetes.

UI	MeSH Term	Description	Entries
D011110	Polymorphism, Genetic	The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.	Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D005075	Biological Evolution	The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.	Evolution, Biological
D005796	Genes	A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.	Cistron,Gene,Genetic Materials,Cistrons,Genetic Material,Material, Genetic,Materials, Genetic
D006239	Haplotypes	The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.	Haplotype
D006681	HLA-D Antigens	Human immune-response or Class II antigens found mainly, but not exclusively, on B-lymphocytes and produced from genes of the HLA-D locus. They are extremely polymorphic families of glycopeptides, each consisting of two chains, alpha and beta. This group of antigens includes the -DR, -DQ and -DP designations, of which HLA-DR is most studied; some of these glycoproteins are associated with certain diseases, possibly of immune etiology.	Antigens, HLA-D,Class II Human Antigens,HLA-Dw Antigens,Human Class II Antigens,Ia-Like Antigens, Human,Immune Response-Associated Antigens, Human,Immune-Associated Antigens, Human,Immune-Response Antigens, Human,HLA-D,HLA-Dw,Immune Response Associated Antigens, Human,Antigens, HLA D,Antigens, HLA-Dw,Antigens, Human Ia-Like,Antigens, Human Immune-Associated,Antigens, Human Immune-Response,HLA D Antigens,HLA Dw Antigens,Human Ia-Like Antigens,Human Immune-Associated Antigens,Human Immune-Response Antigens,Ia Like Antigens, Human,Immune Associated Antigens, Human,Immune Response Antigens, Human
D006683	HLA-DQ Antigens	A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.	HLA-DC Antigens,HLA-MB Antigens,HLA-DC,HLA-DQ,HLA-DS,HLA-DS Antigens,HLA-LB,HLA-LB Antigens,HLA-MB,Antigens, HLA-DC,Antigens, HLA-DQ,Antigens, HLA-DS,Antigens, HLA-LB,Antigens, HLA-MB,HLA DC Antigens,HLA DQ Antigens,HLA DS Antigens,HLA LB Antigens,HLA MB Antigens
D006684	HLA-DR Antigens	A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.	HLA-DR,Antigens, HLA-DR,HLA DR Antigens
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000483	Alleles	Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.	Allelomorphs,Allele,Allelomorph
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