Three allele combinations associated with multiple sclerosis

Olga O. Favorova, Alexander Favorov, Alexey N. Boiko, Timofey V. Andreewski, Marina A. Sudomoina, Alexey D. Alekseenkov, Olga G. Kulakova, Eugenyi I. Gusev, Giovanni Parmigiani, Michael F. Ochs

Research output: Contribution to journalArticle

Abstract

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, TGFβ1, 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: -509TGFβ1*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 CCR5Δ32, DRBI*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.

Original languageEnglish (US)
Article number63
JournalBMC Medical Genetics
Volume7
DOIs
StatePublished - Jul 26 2006
Externally publishedYes

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Multiple Sclerosis
Alleles
Microsatellite Repeats
Genes
Monte Carlo Method
Markov Chains
Immune System Diseases
varespladib methyl
Single Nucleotide Polymorphism
Dissection

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)

Cite this

Favorova, O. O., Favorov, A., Boiko, A. N., Andreewski, T. V., Sudomoina, M. A., Alekseenkov, A. D., ... Ochs, M. F. (2006). Three allele combinations associated with multiple sclerosis. BMC Medical Genetics, 7, [63]. https://doi.org/10.1186/1471-2350-7-63

Three allele combinations associated with multiple sclerosis. / Favorova, Olga O.; Favorov, Alexander; Boiko, Alexey N.; Andreewski, Timofey V.; Sudomoina, Marina A.; Alekseenkov, Alexey D.; Kulakova, Olga G.; Gusev, Eugenyi I.; Parmigiani, Giovanni; Ochs, Michael F.

In: BMC Medical Genetics, Vol. 7, 63, 26.07.2006.

Research output: Contribution to journalArticle

Favorova, OO, Favorov, A, Boiko, AN, Andreewski, TV, Sudomoina, MA, Alekseenkov, AD, Kulakova, OG, Gusev, EI, Parmigiani, G & Ochs, MF 2006, 'Three allele combinations associated with multiple sclerosis', BMC Medical Genetics, vol. 7, 63. https://doi.org/10.1186/1471-2350-7-63
Favorova OO, Favorov A, Boiko AN, Andreewski TV, Sudomoina MA, Alekseenkov AD et al. Three allele combinations associated with multiple sclerosis. BMC Medical Genetics. 2006 Jul 26;7. 63. https://doi.org/10.1186/1471-2350-7-63
Favorova, Olga O. ; Favorov, Alexander ; Boiko, Alexey N. ; Andreewski, Timofey V. ; Sudomoina, Marina A. ; Alekseenkov, Alexey D. ; Kulakova, Olga G. ; Gusev, Eugenyi I. ; Parmigiani, Giovanni ; Ochs, Michael F. / Three allele combinations associated with multiple sclerosis. In: BMC Medical Genetics. 2006 ; Vol. 7.
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AU - Favorova, Olga O.

AU - Favorov, Alexander

AU - Boiko, Alexey N.

AU - Andreewski, Timofey V.

AU - Sudomoina, Marina A.

AU - Alekseenkov, Alexey D.

AU - Kulakova, Olga G.

AU - Gusev, Eugenyi I.

AU - Parmigiani, Giovanni

AU - Ochs, Michael F.

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