Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd1069810.32607/20758251-2011-3-1-85-92ArticlesСтатьиResearch ArticleFamily Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5, RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple SclerosisFamily Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5, RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple SclerosisMakarychevaO YuTsarevaE YuSudomoinaM AKulakovaO GTitovB VBykovaO VGol'tsovaN VKuzenkovaL MBoikoA NFavorovaO Oolga_favorova@mail.ruRussian Cardiology Scientific and Production CenterRussian State Medical UniversityScientific Center of Children Health, Russian Academy of Medical SciencesScientific Center of Children Health, Russian Academy of Medical SciencesRussian Cardiology Scientific and Production CenterRussian State Medical University1503201131VOL 3, NO1 (2011)ТОМ 3, №1 (2011)859217012020Copyright ©; 2011, Makarycheva O.Y., Tsareva E.Y., Sudomoina M.A., Kulakova O.G., Titov B.V., Bykova O.V., Gol'tsova N.V., Kuzenkova L.M., Boiko A.N., Favorova O.O.Copyright ©; 2011, Makarycheva O.Y., Tsareva E.Y., Sudomoina M.A., Kulakova O.G., Titov B.V., Bykova O.V., Gol'tsova N.V., Kuzenkova L.M., Boiko A.N., Favorova O.O.2011Makarycheva O.Y., Tsareva E.Y., Sudomoina M.A., Kulakova O.G., Titov B.V., Bykova O.V., Gol'tsova N.V., Kuzenkova L.M., Boiko A.N., Favorova O.O.Makarycheva O.Y., Tsareva E.Y., Sudomoina M.A., Kulakova O.G., Titov B.V., Bykova O.V., Gol'tsova N.V., Kuzenkova L.M., Boiko A.N., Favorova O.O.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/10698

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS. We investigated the association and linkage with MS of the following immune-system genes polymorphisms: HLA-DRB1, CTLA4, TGFB1, IL4, CCR5 and RANTES, as well as of the matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1) genes polymorphisms. For this purpose we used the transmission disequilibrium test (TDT). The group investigated was comprised of 100 nuclear families of Russian ethnicity, each consisting of an affected offspring and his nonaffected parents. It was found that HLA-DRB1*15 allele and MMP9*-1562C allele were transmitted from healthy heterozygous parents to affected children more frequently than alternative alleles (p = 0.02 and p = 0.04, respectively). Another family-based method, AFBAC (affected family-based control), showed MS association with HLA-DRB1*15, but not with the MMP9*-1562C allele.

functional genomicshumanmultiple sclerosisgenotypingCCR5 geneCTLA4 geneHLA-DRB1 geneIL4 geneMMP9 geneRANTES geneTGFB1 geneTIMP1 geneallelic polymorphismTDTAFBACDyment D.A., Ebers G.C., Sadovnick A.D. // Lancet Neurol. 2004. V. 3. N 2. P. 104-110.Favorova O.O., Kulakova O.G., Boiko A.N. // Genetika. 2010. V. 46. N 3. P. 302-313.Risch N.J. // Nature. 2000. V. 405. N 6788. P 847-856.Hattersley A.T., McCarthy M.I. // Lancet. 2005. V. 366. N 9493. P. 1315-1323.Spielman R.S., McGinnis R.E., Ewens W.J. // Am. J. Hum. Genet. 1993. V. 52. N 3. P 506-516.Spielman R.S., Ewens W.J. // Am. J. Hum. Genet. 1996. V. 59. N 5. P 983-989.Marrosu M.G., Murru R., Costa G., Melis M.C., Rolesu M., Schirru L., Solla E., Cuccu S., Secci M.A., Whalen M.B., et al. // BMC Genet. 2007. V. 8. P 25.Cuturier N., Gourraud PA., Cournu-Rebeix I., Gout C., Bucciarelli F., Edan G., Babron M.C., Clerget-Darpoux F., Clanet M., Fontaine B., Brassat D. // Eur. J. Hum. Genet. 2009. V. 17. N 6. P 844-847.D’Alfonso S., Bolognesi E., Guerini F.R., Barizzone N., Bocca S., Ferrante D., Castelli L., Bergamaschi L., Agliardi C., Ferrante P, et al. // Genes Immun. 2008. V. 9. N 1. P 7-15.Chao M.J., Barnardo M.C., Lui G.Z., Lincoln M.R., Ramagopalan S.V., Herrera B.M., Dyment D.A., Sadovnick A.D., Ebers G.C. // Hum. Mol. Genet. 2007. V. 16. N 16. P 1951-1958.Boiko A.N., Gusev E.I., Sudomoina M.A., Alekseenkov A.D., Kulakova O.G., Bikova O.V., Maslova O.I., Guseva M.R., Boiko S.Y., Guseva M.E., Favorova O.O. // Neurology. 2002. V. 58. N 4. P. 658-660.Makarycheva O.Yu., Tsareva E.Yu., Sudomoina M.A., Kulakova O.G., Bikova O.V., Gol’tsova N.V., Kuzenkova L.M., Boiko A.N., Favorova O.O. // Molekularnaya Biologia. 2010. V. 44. N 5. P. 824-830.Hafler D.A., Compston A., Sawcer S., Lander E.S., Daly M.J., De Jager PL., de Bakker PI., Gabriel S.B., Mirel D.B., Ivinson A.J., et al. // N. Engl. J. Med. 2007. V. 357. N 9. P. 851-862.Willer C.J., Dyment D.A., Cherny S., Ramagopalan S.V., Herrera B.M., Morrison K.M., Sadovnick A.D., Risch N.J., Ebers G.C. // J. Hum. Genet. 2007. V. 52. N 12. P 955-962.Giedraitis V., Modin H., Callander M., Landtblom A.M., Fossdal R., Stefansson K., Hillert J., Gulcher J. // Genes Immun. 2003. V. 4. N 8. P. 559-563.Thomson G. // Am. J. Hum. Genet. 1995. V. 57. N 2. P 487-498.Liguori M., Sawcer S., Setakis E., Compston A., Giordano M., D’Alfonso S., Mellai M., Malferrari G., Trojano M., Livrea P, et al. // J. Neuroimmunol. 2003. V. 143. N 1-2. P 97-100.Lampis R., Morelli L., Congia M., Macis M.D., Mulargia A., Loddo M., De Virgiliis S., Marrosu M.G., Todd J.A., Cucca F. // Hum. Mol. Genet. 2000. V. 9. N 20. P 2959-2965.Yeo T.W., Roxburgh R., Maranian M., Singlehurst S., Gray J., Hensiek A., Setakis E., Compston A., Sawcer S. // J. Neuroimmunol. 2003. V. 143. N 1-2. P 53-59.Goris A., Sawcer S., Vandenbroeck K., Carton H., Billiau A., Setakis E., Compston A., Dubois B. // J. Neuroimmunol. 2003. V. 143. N 1-2. P 65-69.Alizadeh M., Genin E., Babron M.C., Birebent B., Cournu-Rebeix I., Yaouanq J., Dreano S., Sawcer S., Compston A., Clanet M., et al. // J. Neuroimmunol. 2003. V. 143. N 1-2. P 74-78.Schulze T.G., McMahon F.J. // Am. J. Med. Genet. 2002. V. 114. N 1. P 1-11.Racke M.K., Ratts R.B., Arredondo L., Perrin P.J., Lovett-Racke A. // J. Neuroimmunol. 2000. V. 107. N 2. P 205-215.Imitola J., Chitnis T., Khoury S.J. // Pharmacology and Therapeutics. 2005. V. 106. P 163-177.Szczucinski A., Losy J. // Acta Neurol. Scand. 2007. V. 115. N 3. P 137-146.Ram M., Sherer Y., Shoenfeld Y. // J. Clin. Immunol. 2006. V. 26. N 4. P. 299-307.Grainger D.J., Heathcote K., Chiano M., Snieder H., Kemp PR., Metcalfe J.C., Carter N.D., Spector T.D. // Hum. Mol. Genet. 1999. V. 8. P 93-97.Rosenwasser L.J., Klemm D.J., Dresback J.K., Inamura H., Mascali J. J., Klinnert M., Borish L. // Clin. Exp. Allergy. 1995. V. 25. N 2. Suppl. P. 74-78.Nickel R.G., Casolaro V., Wahn U., Beyer K., Barnes K.C., Plunkett B.S., Freidhoff L.R., Sengler C., Plitt J.R., Schleimer R.P., et al. // J. Immunol. 2000. V. 164. P. 1612-1616.Zhang B., Ye S., Herrmann S.M., Eriksson P., de Maat M., Evans A., Arveiler D., Luc G., Cambien F., Hamsten A., et al. // Circulation. 1999. V. 99. P 1788-1794.Ligers A., Teleshova N., Masterman T., Huang W.X., Hillert J. // Genes Immun. 2001. V. 2. P 145-152.McDonald W.I., Compston A., Edan G., Goodkin D., Hartung H.P, Lublin F.D., McFarland H.F., Paty D.W., Polman C.H., Reingold S.C., et al. // Ann. Neurol. 2001. V. 50. N 1. P 121-127.Sambrook J., Fritsch E.F., Maniatis T. // Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, N.Y.: Cold Spring Harbor Lab. Press, 1989. 923 p.Marron M.P., Raffel L.J., Garchon H.J., Jacob C.O., Serrano-Rios M., Martinez Larrad M.T., Teng W.P, Park Y., Zhang Z.X., Goldstein D.R., et al. // Hum. Mol. Genet. 1997. V. 6. N 8. P 1275-1282.Laird N.M., Horvath S., Xu X. // Genet. Epidemiol. 2000. V. 19. N 1. Suppl. P S36-S42.Sudomoina M.A., Boiko A.N., Demina T.L., Gusev E.I., Boldyreva M.N., Trofimov D. Yu., Alekseev L.P., Favorova O.O. // Molekulyarnaya Biologia. 1998. V. 32. P. 291-296.Favorova O.O., Favorov A.V., Boiko A.N., Andreewski T.V., Sudomoina M.A., Alekseenkov A.D., Kulakova O.G., Gusev E.I., Parmigiani G., Ochs M.F. // BMC Med. Genet. 2006. V. 7. P. 63.Favorova O.O., Andreewski T.V., Boiko A.N., Sudomoina M.A., Alekseenkov A.D., Kulakova O.G., Slanova A.V., Gusev E.I. // Neurology. 2002. V. 59. N 2. P 1652-1655.Andreewski T.V., Sudomoina M.A., Gusev E.I., Boiko A.N., Alekseenkov A.D., Favorova O.O. // Molekulyarnaya Biologia. 2002. V. 36. N 4. P. 643-648.Ristic S., Lovrecic L., Starcevic-Cizmarevic N., Brajenovic-Milic B., Jazbec S.S., Barac-Latas V., Vejnovic D., Sepcic J., Kapovic M., Peterlin B. // Mult. Scler. 2006. V. 12. N 3. P 360-362.Silversides J.A., Heggarty S.V., McDonnell G.V., Hawkins S.A., Graham C.A. // Mult. Scler. 2004. V. 10. N 2. P 149-152.Pulkkinen K., Luomala M., Kuusisto H., Lehtimaki T., Saarela M., Jalonen T.O., Elovaara I. // Acta Neurol. Scand. 2004. V. 109. N 5. P 342-347.Malferrari G., Stella A., Monferini E., Saltini G., Proverbio M.C., Grimaldi L.M., Rossi-Bernardi L., Biunno I. // Exp. Mol. Pathol. 2005. V. 78. N 1. P 55-57.Rasmussen H.B., Kelly M.A., Francis D.A., Clausen J. // J. Neurol. Sci. 2001. V. 184. N 2. P 143-147.Fukazawa T., Yanagawa T., Kikuchi S., Yabe I., Sasaki H., Hamada T., Miyasaka K., Gomi K., Tashiro K. // J. Neurol. Sci. 1999. V. 171. No 1. P. 49-55.Arthur A.T., Armati P. J., Bye C., Heard R.N., Stewart G.J., Pollard J.D., Booth D.R. // BMC Med. Genet. 2008. V. 9. P. 17.Weinshenker B.G., Hebrink D., Kantarci O.H., Schaefer-Klein J., Atkinson E., Schaid D., McMurray C.M. // J. Neuroimmunol. 2001. V. 120. N 1-2. P. 138-145.Green A.J., Barcellos L.F., Rimmler J.B., Garcia M.E., Caillier S., Lincoln R.R., Bucher P., Pericak-Vance M.A., Haines J.L., Hauser S.L., Oksenberg J.R. // J. Neuroimmunol. 2001. V. 116. N 1. P. 116-124.Zivkovic M., Djuric T., Dincic E., Raicevic R., Alavantic D., Stankovic A. // J. Neuroimmunol. 2007. V. 189. N 1-2. P. 147-150.Benesova Y., Vasku A., Stourac P., Hladikova M., Beranek M., Kadanka Z., Novotna H., Bednarik J. // J. Neuroimmunol. 2008. V. 205. N 1-2. P. 105-109.Mirowska-Guzel D., Gromadzka G., Czlonkowski A., Czlonkowska A. // J. Neuroimmunol. 2009. V. 214. N 1-2. P. 113-117.Akkad D.A., Arning L., Ibrahim S.M., Epplen J.T. // Genes Immun. 2007. V. 8. N 8. P. 703-706.Urcelay E., Santiago J.L., Mas A., Martinez A., de Las Heras V., Arroyo R., de la Concha E.G. // J. Neuroimmunol. 2005. V. 168. N 1-2. P. 164-167.Kamali-Sarvestani E., Nikseresht A., Aflaki E., Sarvari J., Gharesi-Fard B. // Acta Neurol. Scand. 2007. V. 115. N 3. P. 161-166.Gade-Andavolu R., Comings D.E., MacMurray J., Vuthoori R.K., Tourtellotte W.W., Nagra R.M., Cone L.A. // Mult. Scler. 2004. V. 10. N 5. P. 536-539.