Polymorphism of chemokine receptor gene CCR5 in multiple sclerosis patients and in healthy subjects in the Siberian region
https://doi.org/10.20538/1682-0363-2006-3-98-104
Abstract
Multiple sclerosis is chronic inflammatory disease of the central nervous system in the development of which chemokines of the type Tx1 play the leading role. Chemokines and their receptors participate in the development of multiple sclerosis as a result of drawing immune cells into central nervous system. Mutation of CCR5 delta32 decreases functional activity of the appropriate receptor on cellular surface and thus can reduce migration of leucocytes into foci of injury. Aimed at studying the role of mutation in multiple sclerosis, we compared frequency of gene type CCR5 in peripheral mononuclears of 102 multiple sclerosis patients and in 136 healthy subjects. The results obtained allow to conclude that polymorphism of chemokine receptor gene CCR5del32 is not a leading factor in the susceptibility to multiple sclerosis in the studied population.
About the Authors
Yu. Yu. Orlova
Сибирский государственный медицинский университет
Russian Federation
Russian Federation
V. M. Alifirova
Сибирский государственный медицинский университет
Russian Federation
Russian Federation
N. V. Cherdyntseva
Сибирский государственный медицинский университет
Russian Federation
Russian Federation
P. A. Gervas
НИИ онкологии ТНЦ СО РАМН
Russian Federation
Russian Federation
References
1. Галеева А.Р., Хаснутдинова Э.К., Сломинский П.А., Лимборская С.А. Распространенность делеции 32 п.н. в гене рецептора хемокинов CCR5 в популяциях Волго-Уральского региона // Генетика. 1998. Т. 34. № 8. С. 1160—1162.
2. Гусев Е.И., Бойко А.Н. Рассеянный склероз: от изучения иммунопатогенеза к новым методам лечения. М., 2001. 128 с.
3. Завалишин И.А., Захарова М.Н. Рассеянный склероз: основные аспекты патогенеза // Рассеянный склероз и другие демиелинизирующие заболевания / Под ред. Е.И. Гусева, И.А. Завалишина, А.Н. Бойко. М.: Миклош, 2004. С. 60—74.
4. Иерусалимский А.П., Малкова Н.А. Эпидемиологические исследования и их роль в изучении рассеяного склероза // Рассеянный склероз. Избранные вопросы теории и практики / Под ред. И.А. Завалишина, В.И. Головкина. М., 2000. С. 510—536.
5. Посвалюк Н.Э., Козлова Т.А., Цеферман А.Г. Клинико-эпидемиологическая характеристика рассеянного склероза в Хабаровском крае // Рассеянный склероз (эпидемиология, новые методы диагностики). Новосибирск, 1985. С. 10—12.
6. Сломинский П.А., Шадрина М.И., Спицын В.А. и др. Простой и быстрый метод определения делеции 32 п.н. в гене рецептора хемокинов CCR5 // Генетика. 1997. Т. 33. № 11. С. 1596—1598.
7. Ходос Х.Г., Кожова И.И. Рассеяный склероз. Иркутск: Восточ.-Сиб. кн. изд-во, 1980. 176 с.
8. Ebers G.C., Kukay K., Bulman D.E. et al. A full genome search in multiple sclerosis // Nat. Genet 1996. № 13. P. 472—476.
9. Sawcer S., Jones H.B., Feakes R. et al. A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22 // Nat. Genet. 1996. № 13. P.464—468.
10. Garred P., Madsen H., Petersen J. et al. CC chemokine receptor 5 polymorphism in rheumatoid arthritis // J. Rheumatol. 1998. № 25. P. 1462—1465.
11. Barcellos L.F., Schito A.M., Rimmler J.B. et al. CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis // Immunogenetics. 2000. № 51. P. 281—288.
12. Sellebjerg F., Madsen H.O., Jensen C.V. et al. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis // J. Neuroimmunol. 2000. № 102 (1). P. 98—106.
13. Balashov K.E., Rottman J.B., Weiner H.L., Hancock W.W. CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions // Proc. Natl. Acad. Sci. USA. 1999. № 96 (12). P. 6873—6878.
14. Trebst C., Staugaitis S.M., Tucky B. et al. Chemokine receptors on infiltrating leucocytes in inflammatory pathologies of the central nervous system (CNS) // Neuropathol. Appl. Neurobiol. 2003. № 29 (6). P. 584—595.
15. Karni A., Balashov K., Hancock W.W. et al. Cyclophosphamide modulates CD4+ T cells into a T helper type 2 phenotype and reverses increased IFN-gamma production of CD8+ T cells in secondary progressive multiple sclerosis // J. Neuroimmunol. 2004. № 146 (1—2). P. 189—198.
16. Brühl H., Cihak J., Stangassinger M. et al. Depletion of CCR5-expressing cells with bispecific antibodies and chemokine toxins: a new strategy in the treatment of chronic inflammatory diseases and HIV // The Journal of Immunology. 2001. № 166. P. 2420—2426.
17. Jalonen T.O., Pulkkinen K., Ukkonen M. et al. Differential intracellular expression of CCR5 and chemokines in multiple sclerosis subtypes // J. Neurol. 2002. № 249 (5). P. 576—583.
18. Schreiber K., Otura A.B., Ryder L.P. et al. Disease severity in Danish multiple sclerosis patients evaluated by MRI and three genetic markers (HLA-DRB1*1501, CCR5 deletion mutation, apolipoprotein E) // Mult. Scler. 2002. № 8 (4). P. 295—298.
19. Yudin N.S., Vinogradov S.V., Potapova T.A. et al. Distribution of CCR5-delta 32 gene deletion across the Russian part of Eurasia // Hum. Genet. 1998. № 102. P. 695—698.
20. Jagodzinski P.P., Lecybyl R., Ignacak M. et al. Distribution of Δ32 alelle of the CCR5 gene in population of Poland // J. Med. Genet. 2000. № 45. P. 271—274.
21. Ebers G.C., Bulman D. The geography of MS reflects genetic susceptibility // Neurology. 1986. № 36. P. 108.
22. Sorensen T.L., Tani M., Jensen J. et al. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients // J. Clin. Invest. 1999. № 103 (6). P. 807—815.
23. Martinson J.J., Chapman N.H., Rees D.C. et al. Global distribution of the CCR5 gene 32-basepair deletion // Nature genetics. 1997. № 16. P. 100—103.
24. Haase C.G., Schmidt S., Faustman P.M. Frequencies of the G-protein beta 3 subunit C825T polymorphism and the D32 mutation of the chemokine receptor-5 in patients with multiple sclerosis // Neurosci. Lett. 2002. V. 27. № 330 (3). P. 293—295.
25. Pulkkinen K., Luomala M., Kuusisto H. et al. Increase in CCR5 D32/D32 genotype in multiple sclerosis // Acta Neurol. Scand. 2004. № 109 (5). P. 342—347.
26. Silversides J.A., Heggarty S.V., McDonnell G.V. et al. Influence of CCR5 delta32 polymorphism on multiple sclerosis susceptibility and disease course // Multiple Sclerosis. 2004. № 10 (2). P. 149—152.
27. Balanovsky O., Pocheshkhova E., Pshenichnov A. et al. Is spatial distribution of the HIV-1-Resistant CCR5Δ32 allele formed by ecological factors? // J. of Physiological anthropology and applied human science. 2005. № 24. P. 375—382.
28. Kantor R., Bakhanashvili M., Achiron A. A mutated CCR5 gene may have favorable prognostic implications in MS // Neurology. 2003. V. 22. № 61 (2). P. 238—240.
29. Kurtzke J.F., Beebe J.W., Norman J.E. Epidemiology of multiple sclerosis in US veterans. Part I. Race, sex and geographic distribution // Neurology. 1979. № 29. P. 1228—1235.
30. Murphy P.M., Baggiolini M., Charo I.F. et al. Nomenclature for chemokine receptors // Pharmacological reviews. 2001. № 52 (1). P. 1245—1273.
31. Hvas J., McLean C., Justesen J. Perivascular T cells express the proinflammatory chemokine RANTES mRNA in multiple sclerosis lesions // Scand. J. Immunol. 1997. № 46. P. 195—203.
32. Sadovnick A.D., Ebers G.C. Epidemiology of multiple sclerosis: a critical overview // Can. J. Neurol. Sci. 1993. № 20 (1). P. 17—29.
33. Sallusto F., Lanzavecchia A., Mackay C.R. Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses // Immunol. Today. 1998. № 19. P. 568—574.
34. Bennetts B.H., Teutsch S.M., Buhler M.M. et al. The CCR deletion mutation fails to protect against multiple sclerosis // Hum Immunology. 1997. № 58 (1). P. 52—59.
35. Favorova O.O., Andreewski T.V., Boiko A.N. et al. The chemokine receptor CCR5 deletion mutation is associated with MS in HLA-DR4-positive Russians // Neurology. 2002. № 59. P. 1652—1655.
36. Trebst C., Ransohoff R.M. Investigating chemokines and chemokine receptors in patients with multiple sclerosis: opportunities and challenges // Arch. Neurol. 2001. № 58. P. 1975—1980.
Review
For citations:
Orlova Yu.Yu., Alifirova V.M., Cherdyntseva N.V., Gervas P.A. Polymorphism of chemokine receptor gene CCR5 in multiple sclerosis patients and in healthy subjects in the Siberian region. Bulletin of Siberian Medicine. 2006;5(3):98-104. (In Russ.) https://doi.org/10.20538/1682-0363-2006-3-98-104
Views:
497
Email this article 