J Clin Neurol.  2007 Sep;3(3):133-138. 10.3988/jcn.2007.3.3.133.

CCR2-64I and CCR5Delta32 Polymorphisms in Korean Patients with Myasthenia Gravis

Affiliations
  • 1Department of Neurology, Pochon CHA University, College of Medicine, Korea.
  • 2Department of Neurology, Pusan National University School of Medicine, Korea.
  • 3Department of Neurology, Brain Korea 21 Project for Medicine, Yonsei University College of Medicine, Korea. ycchoi@yumc.yonsei.ac.kr

Abstract

BACKGROUND AND PURPOSE
Chemokines participate in the regulation of immune and inflammatory responses by interacting with their receptors, which are primarily expressed on immune and inflammatory cells such as B- and T-lymphocytes and antigen-presenting cells. Chemokines and their receptors are therefore considered to mediate inflammation and tissue damage in autoimmune disorders. Chemokine receptor (CCR) genotypes were recently identified, and the importance of their genetic polymorphisms in some autoimmune and infectious disorders has been demonstrated. To define the roles of the polymorphism of the CCR2 gene at codon 64 (CCR2-64I) and the 32-bp deletion in the coding region of CCR5 (CCR5Delta32) in Korean patients with myasthenia gravis (MG), we compared these genotypes in MG cases and healthy controls and investigated the clinical features associated with these genotypes.
METHODS
One hundred and fifteen healthy controls (51 men and 64 women) and 109 MG patients (44 men and 65 women) from three University hospitals were included. We examined each patient for clinical features using electrophysiology tests, laboratory tests, and thymic pathology. The CCR2-64I and CCR5Delta32 polymorphisms were determined by the PCR-RFLP method.
RESULTS
We detected no difference in the frequencies of CCR2-64I polymorphism between MG patients and healthy controls. All of the MG patients and the healthy controls were homozygous for the wild-type CCR5 genotype. The results of electrophysiological tests and thymic pathologies were not influenced by the type of CCR2-64I polymorphism. However, the anti-acetylcholine-receptor (AChR) antibody titer was higher in the CCR2 G/G genotype (13.34+/-12.71 nmol/L) than in the CCR2 A/A genotype (5.83+/-2.56 nmol/L).
CONCLUSIONS
We found no evidence of an increased risk for MG associated with the CCR2-64I and CCR5Delta32 polymorphisms. However, the increased anti-AChR antibody titer in the patients with the CCR2 G/G genotype suggests that the CCR2 gene play a role in the pathophysiology of MG.

Keyword

Myasthenia gravis; Chemokine receptor; CCR2-64I; CCR5Delta32; Anti-AChR antibody titer

MeSH Terms

Antigen-Presenting Cells
Chemokines
Clinical Coding
Codon
Electrophysiology
Genotype
Hospitals, University
Humans
Inflammation
Male
Myasthenia Gravis*
Pathology
Polymorphism, Genetic
T-Lymphocytes
Chemokines
Codon

Reference

1. Feferman T, Maiti PK, Berrih-Aknin S, Bismuth J, Bidault J, Fuchs S, et al. Overexpression of IFN-induced protein 10 and its receptor CXCR3 in myasthenia gravis. J Immunol. 2005. 174:5324–5331.
Article
2. Huang D, Pirskanen R, Hjelmstrom P, Lefvert AK. Polymorphisms in IL-1beta and IL-1 receptor antagonist genes are associated with myasthenia gravis. J Neuroimmunol. 1998. 81:76–81.
Article
3. Huang DR, Pirskanen R, Matell G, Lefvert AK. Tumour necrosis factor-alpha polymorphism and secretion in myasthenia gravis. J Neuroimmunol. 1999. 94:165–171.
4. Huang D, Liu J, Noren K, Xia SQ, Trifunovic J, Pirskanen R, et al. Genetic association of Ctla-4 to myasthenia gravis with thymoma. J Neuroimmunol. 1998. 88:192–198.
Article
5. Vieira MA, Caillat-Zucman S, Gajdos P, Cohen-Kaminsky S, Casteur A, Bach JF. Identification by genomic typing of non-DR3 HLA class II gene associated with myasthenia gravis. J Neuroimmunol. 1994. 47:115–122.
Article
6. van der Pol WL, Jansen MD, Kuks JB, de Baets M, Leppers-van de Straat FG, Wokke JH, et al. Association of the Fc gamma receptor IIA-R/R131 genotype with myasthenia gravis in Dutch patients. J Neuroimmunol. 2003. 144:143–147.
Article
7. Giraud M, Eymard B, Tranchant C, Gajdos P, Garchon HJ. Association of the gene encoding the delta-subunit of the muscle acetylcholine receptor (CHRND) with acquired autoimmune myasthenia gravis. Genes Immun. 2004. 5:80–83.
Article
8. Bonifati DM, Willcox N, Vincent A, Beeson D. Lack of association between acetylcholine receptor epsilon polymorphisms and early-onset myasthenia gravis. Muscle Nerve. 2004. 29:436–439.
Article
9. Luster AD. Chemokines - chemotactic cytokines that mediate inflammation. N Engl J Med. 1998. 338:436–445.
Article
10. Zhao X, Gharizadeh B, Hjelmstrom P, Pirskanen R, Nyren P, Lefvert AK, et al. Genotypes of CCR2 and CCR5 chemokine receptors in human myasthenia gravis. Int J Mol Med. 2003. 12:749–753.
Article
11. Strieter RM, Standiford TJ, Huffnagle GB, Colletti LM, Lukacs NW, Kunkel SL. "The good, the bad, and the ugly." The role of chemokines in models of human disease. J Immunol. 1996. 156:3583–3586.
12. Miyagishi R, Kikuchi S, Takayama C, Inoue Y, Tashiro K. Identification of cell types producing RANTES, MIP-1 alpha and MIP-1 beta in rat experimental autoimmune encephalomyelitis by in situ hybridization. J Neuroimmunol. 1997. 77:17–26.
Article
13. Favorova OO, Andreewski TV, Boiko AN, Sudomoina MA, Alekseenkov AD, Kulakova OG, et al. The chemokine receptor CCR5 deletion mutation is associated with MS in HLA-DR4-positive Russians. Neurology. 2002. 59:1652–1655.
Article
14. Saito R, Onodera H, Tago H, Suzuki Y, Shimizu M, Matsumura Y, et al. Altered expression of chemokine receptor CXCR5 on T cells of myasthenia gravis patients. J Neuroimmunol. 2005. 170:172–178.
Article
15. Petrek M, Drabek J, Kolek V, Zlamal J, Welsh KJ, Bunce M, et al. CC chemokine receptor gene polymorphisms in Czech patients with pulmonary sarcoidosis. Am J Respir Crit Care Med. 2000. 162:1000–1003.
Article
16. Wang FS, Hong WG, Cao Y, Liu MX, Jin L, Hu LP, et al. Population survey of CCR5 delta32, CCR5 m303, CCR2b 64I, and SDF1 3'A allele frequencies in indigenous Chinese healthy individuals, and in HIV-1-infected and HIV-1-uninfected individuals in HIV-1 risk groups. J Acquir Immune Defic Syndr. 2003. 32:124–130.
Article
17. De Pinho Lott Carvalhaes FA, Cardoso GL, Hamoy IG, Liu YT, Guerreiro JF. Distribution of CCR5-delta32, CCR2-64I, SDF1-3'A mutations in populations from the Brazilian Amazon Region. Hum Biol. 2004. 76:643–646.
18. Gharagozloo M, Doroudchi M, Farjadian S, Pezeshki AM, Ghaderi A. The frequency of CCR5Delta32 and CCR2-64I in southern Iranian normal population. Immunol Lett. 2005. 96:277–281.
Article
19. Oh MD, Kim SS, Kim EY, Lee S, Kim N, Park KY, et al. The frequency of mutation in CCR5 gene among Koreans. Int J STD AIDS. 2000. 11:266–267.
Article
20. Martison JJ, Hong L, Karanicolas R, Moore JP, Kostrikis LG. Global distribution of the CCR2-64I/CCR5-59653T HIV-1 disease-protective haplotype. AIDS. 2000. 14:483–489.
Article
21. Poea-Guyon S, Christadoss P, Le Panse R, Guyon T, De Baets M, Wakkach A, et al. Effects of cytokines on acetylcholine receptor expression: implications for myasthenia gravis. J Immunol. 2005. 174:5941–5949.
Article
22. Shi FD, Zhang GX, Bai XF, Van der Meide PH, Link H. Cellular mRNA expression of interferon-gamma (IFN-gamma), IL-4 and IL-10 relates to resistance to experimental autoimmune myasthenia gravis (EAMG) in young Lewis rats. Clin Exp Immunol. 1997. 108:523–528.
Article
23. Reyes-Reyna S, Krolick KA. Chemokine production by rat myocytes exposed to interferon-gamma. Clin Immunol. 2000. 94:105–113.
24. Charo IF, Myers SJ, Herman A, Franci C, Connolly AJ, Coughlin SR. Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proc Natl Acad Sci U S A. 1994. 91:2752–2756.
Article
25. Gu D, Wogensen L, Calcutt NA, Xia C, Zhu S, Merlie JP, et al. Myasthenia gravis-like syndrome induced by expression of interferon gamma in the neuromuscular junction. J Exp Med. 1995. 181:547–557.
Article
26. Rottman JB, Ganley KP, Williams K, Wu L, Mackay CR, Ringler DJ. Cellular localization of the chemokine receptor CCR5. Correlation to cellular targets of HIV-1 infection. Am J Pathol. 1997. 151:1341–1351.
27. Reyes-Reyna S, Stegall T, Krolick KA. Muscle responds to an antibody reactive with the acetylcholine receptor by up-regulating monocyte chemoattractant protein 1: a chemokine with the potential to influence the severity and course of experimental myasthenia gravis. J Immunol. 2002. 169:1579–1586.
Article
28. Broder CC, Collman RG. Chemokine receptors and HIV. J Leukoc Biol. 1997. 62:20–29.
Article
29. Siebert H, Sachse A, Kuziel WA, Maeda N, Bruck W. The chemokine receptor CCR2 is involved in macrophage recruitment to the injured peripheral nervous system. J Neuroimmunol. 2000. 110:177–185.
Article
30. Galimberti D, Fenoglio C, Lovati C, Gatti A, Guidi I, Venturelli E, et al. CCR2-64I polymorphism and CCR5 Delta32 deletion in patients with Alzheimer's disease. J Neurol Sci. 2004. 225:79–83.
Article
31. Drachman DB, Adams RN, Josifek LF, Self SG. Functional activities of autoantibodies to acetylcholine receptors and the clinical severity of myasthenia gravis. N Engl J Med. 1982. 307:769–775.
Article
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