PD-1 Gene Polymorphism in Children with Subacute Sclerosing Panencephalitis

 

 Buy Article Permissions and Reprints

Abstract

Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory and degenerative disorder of the central nervous system. Several factors influence the risk of chronic brain infection with the mutant measles virus. However, to date, no pathogenic mechanism that may predispose to SSPE has been determined. Studies have indicated that specific polymorphisms in certain host genes are probably involved in impairing the ability of host immune cells to eradicate the measles virus in SSPE patients. Programmed cell death protein 1 (PD-1), a member of the CD28 family, is a negative regulator of the immune system. The purpose of our study was to investigate whether PD-1 gene polymorphisms affect susceptibility to the development of SSPE in Turkish children. In total, 109 subjects (54 SSPE patients and 55 healthy controls) were genotyped for the PD-1.9 C/T (rs2227982) single-nucleotide polymorphism (SNP). The distributions of T alleles in the PD-1.9 polymorphism in SSPE patients and healthy controls were 2.8 and 10.9%, respectively. There was a statistically significant difference between the groups; the 95% confidence interval (CI) was 0.06 to 0.85 and the odds ratio (OR) was 0.23 (χ² test). Thus, we identified an association between SSPE and the PD-1 rs2227982 gene polymorphism; the frequency of T alleles was higher in controls than in SSPE patients.

• References

• 1 Garg RK. Subacute sclerosing panencephalitis. J Neurol 2008; 255 (12) 1861-1871
  CrossrefPubMedGoogle Scholar
• 2 Gascon GG. Subacute sclerosing panencephalitis. Semin Pediatr Neurol 1996; 3 (4) 260-269
  CrossrefPubMedGoogle Scholar
• 3 Tuxhorn IE. Familial subacute sclerosing panencephalitis in two siblings. Pediatr Neurol 2004; 31 (4) 291-294
  CrossrefPubMedGoogle Scholar
• 4 Inoue T, Kira R, Nakao F , et al. Contribution of the interleukin 4 gene to susceptibility to subacute sclerosing panencephalitis. Arch Neurol 2002; 59 (5) 822-827
  CrossrefPubMedGoogle Scholar
• 5 Torisu H, Kusuhara K, Kira R , et al. Functional MxA promoter polymorphism associated with subacute sclerosing panencephalitis. Neurology 2004; 62 (3) 457-460
  CrossrefPubMedGoogle Scholar
• 6 Yılmaz V, Demirbilek V, Gürses C , et al. Interleukin (IL)-12, IL-2, interferon-γ gene polymorphisms in subacute sclerosing panencephalitis patients. J Neurovirol 2007; 13 (5) 410-415
  CrossrefPubMedGoogle Scholar
• 7 Yentür SP, Gürses C, Demirbilek V , et al. Alterations in cell-mediated immune response in subacute sclerosing panencephalitis. J Neuroimmunol 2005; 170 (1–2) 179-185
  CrossrefPubMedGoogle Scholar
• 8 Hara T, Yamashita S, Aiba H , et al. Measles virus-specific T helper 1/T helper 2-cytokine production in subacute sclerosing panencephalitis. J Neurovirol 2000; 6 (2) 121-126
  CrossrefPubMedGoogle Scholar
• 9 Nagano I, Nakamura S, Yoshioka M, Onodera J, Kogure K, Itoyama Y. Expression of cytokines in brain lesions in subacute sclerosing panencephalitis. Neurology 1994; 44 (4) 710-715
  CrossrefPubMedGoogle Scholar
• 10 Shinohara T, Taniwaki M, Ishida Y, Kawaichi M, Honjo T. Structure and chromosomal localization of the human PD-1 gene (PDCD1). Genomics 1994; 23 (3) 704-706
  CrossrefPubMedGoogle Scholar
• 11 Wang SC, Chen YJ, Ou TT , et al. Programmed death-1 gene polymorphisms in patients with systemic lupus erythematosus in Taiwan. J Clin Immunol 2006; 26 (6) 506-511
  CrossrefPubMedGoogle Scholar
• 12 Prokunina L, Padyukov L, Bennet A , et al. Association of the PD-1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope. Arthritis Rheum 2004; 50 (6) 1770-1773
  CrossrefPubMedGoogle Scholar
• 13 Zheng L, Li D, Wang F , et al. Association between hepatitis B viral burden in chronic infection and a functional single nucleotide polymorphism of the PDCD1 gene. J Clin Immunol 2010; 30 (6) 855-860
  CrossrefPubMedGoogle Scholar
• 14 Petrovas C, Casazza JP, Brenchley JM , et al. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. J Exp Med 2006; 203 (10) 2281-2292
  CrossrefPubMedGoogle Scholar
• 15 Ishizaki Y, Yukaya N, Kusuhara K , et al. PD1 as a common candidate susceptibility gene of subacute sclerosing panencephalitis. Hum Genet 2010; 127 (4) 411-419
  CrossrefPubMedGoogle Scholar
• 16 Reuter D, Schneider-Schaulies J. Measles virus infection of the CNS: human disease, animal models, and approaches to therapy. Med Microbiol Immunol (Berl) 2010; 199 (3) 261-271
  CrossrefPubMedGoogle Scholar
• 17 Iwai Y, Terawaki S, Ikegawa M, Okazaki T, Honjo T. PD-1 inhibits antiviral immunity at the effector phase in the liver. J Exp Med 2003; 198 (1) 39-50
  CrossrefPubMedGoogle Scholar
• 18 Zhang G, Liu Z, Duan S , et al. Association of polymorphisms of programmed cell death-1 gene with chronic hepatitis B virus infection. Hum Immunol 2010; 71 (12) 1209-1213
  CrossrefPubMedGoogle Scholar
• 19 Ming ZJ, Hui H, Miao M, Qiu YH, Zhang XG. Polymorphisms in PDCD1 gene are not associated with aplastic anemia in Chinese Han population. Rheumatol Int 2012; 32 (10) 3107-3112
  CrossrefPubMedGoogle Scholar
• 20 Ni R, Ihara K, Miyako K , et al. PD-1 gene haplotype is associated with the development of type 1 diabetes mellitus in Japanese children. Hum Genet 2007; 121 (2) 223-232
  CrossrefPubMedGoogle Scholar