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http://purl.uniprot.org/citations/16872485http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16872485http://www.w3.org/2000/01/rdf-schema#comment"

Background

Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS.

Methods

286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion) of the DRB1, TNF, LT, TGFbeta1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group.

Results

We identified two previously unknown MS-associated tri-allelic combinations:-509TGFbeta1*C, DRB1*18(3), CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2) allele, the microsatellite TNFa9 allele and the biallelic combination CCR5Delta32, DRB1*04 were also reidentified as MS-associated.

Conclusion

These results represent an independent validation of MS association with DRB1*15(2) and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.org/dc/terms/identifier"doi:10.1186/1471-2350-7-63"xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/author"Parmigiani G."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/author"Ochs M.F."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/author"Favorova O.O."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/author"Sudomoina M.A."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/author"Alekseenkov A.D."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/author"Boiko A.N."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/author"Gusev E.I."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/author"Kulakova O.G."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/author"Andreewski T.V."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/author"Favorov A.V."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/name"BMC Med Genet"xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/pages"63"xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/title"Three allele combinations associated with multiple sclerosis."xsd:string
http://purl.uniprot.org/citations/16872485http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/16872485http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16872485
http://purl.uniprot.org/citations/16872485http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/16872485
http://purl.uniprot.org/uniprot/#_A0A0A7C3H3-mappedCitation-16872485http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16872485
http://purl.uniprot.org/uniprot/#_A0A0A7C3I1-mappedCitation-16872485http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16872485
http://purl.uniprot.org/uniprot/#_A0A0A7C3I5-mappedCitation-16872485http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16872485
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