Biomaterial Database

HLA-DQ polymorphisms do not explain HLA class II associations with multiple sclerosis in two Canadian patient groups. 1993

D G Haegert, and G S Francis

Discipline of Pathology, Memorial University of Newfoundland, St. John's, Canada.

Patient sharing of HLA-DQ allelic polymorphisms is a possible explanation for the association of multiple sclerosis (MS) with different HLA class II haplotypes in different populations. We used two-locus linkage analysis to investigate the relevance of three different polymorphisms to MS susceptibility in 79 French Canadian patients and 62 mixed ethnic white patients. In French Canadians, we found that an MS association with shared DQB1 sequences and a DQA1 codon for glutamine at residue 34 is secondary to an MS association with the common DR2 haplotype, DRB1*1501-DQA1*0102-DQB1*0602. In contrast, we found that an MS association in French Canadians with a DQB1 codon for leucine at residue 26 (DQ beta Leu26) is not secondary to an MS association with the DR2-bearing haplotype. Mixed ethnic whites showed a positive MS association with the DR2 haplotype but no MS association with any of these polymorphisms. We conclude that (1) the DR2 haplotype is predispositional for MS in both populations, (2) DQ beta Leu26 is an additional predispositional factor in French Canadians, and (3) none of the DQ polymorphisms fully explains the association of MS with HLA alleles in both patient groups.

UI	MeSH Term	Description	Entries
D008040	Genetic Linkage	The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.	Genetic Linkage Analysis,Linkage, Genetic,Analyses, Genetic Linkage,Analysis, Genetic Linkage,Genetic Linkage Analyses,Linkage Analyses, Genetic,Linkage Analysis, Genetic
D009103	Multiple Sclerosis	An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)	MS (Multiple Sclerosis),Multiple Sclerosis, Acute Fulminating,Sclerosis, Disseminated,Disseminated Sclerosis,Sclerosis, Multiple
D009674	Nova Scotia	A province of eastern Canada, one of the Maritime Provinces with NEW BRUNSWICK; PRINCE EDWARD ISLAND; and sometimes NEWFOUNDLAND AND LABRADOR. Its capital is Halifax. The territory was granted in 1621 by James I to the Scotsman Sir William Alexander and was called Nova Scotia, the Latin for New Scotland. The territory had earlier belonged to the French, under the name of Acadia. (From Webster's New Geographical Dictionary, 1988, p871 & Room, Brewer's Dictionary of Names, 1992, p384)
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
D011792	Quebec	A province of eastern Canada. Its capital is Quebec. The region belonged to France from 1627 to 1763 when it was lost to the British. The name is from the Algonquian quilibek meaning the place where waters narrow, referring to the gradually narrowing channel of the St. Lawrence or to the narrows of the river at Cape Diamond. (From Webster's New Geographical Dictionary, 1988, p993 & Room, Brewer's Dictionary of Names, 1992, p440)
D012150	Polymorphism, Restriction Fragment Length	Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.	RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D005602	France	A country in western Europe bordered by the Atlantic Ocean, the English Channel, the Mediterranean Sea, and the countries of Belgium, Germany, Italy, Spain, Switzerland, the principalities of Andorra and Monaco, and by the duchy of Luxembourg. Its capital is Paris.	Corsica,Saint Pierre and Miquelon,Miquelon and Saint Pierre,Miquelon and St. Pierre,St. Pierre and Miquelon
D005802	Genes, MHC Class II	Genetic loci in the vertebrate major histocompatibility complex that encode polymorphic products which control the immune response to specific antigens. The genes are found in the HLA-D region in humans and include H-2M, I-A, and I-E loci in mice.	Class II Genes,Genes, Class II,Genes, HLA Class II,MHC Class II Genes,Class II Gene,Gene, Class II
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
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