Association of CD22 gene polymorphism with susceptibility to limited cutaneous systemic sclerosis

Authors

  • Y. Hitomi,

    1. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    Search for more papers by this author
  • N. Tsuchiya,

    Corresponding author
    1. Doctoral Program in Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
      Naoyuki Tsuchiya, MD, PhD
      Doctoral Program in Social and Environmental Medicine
      Graduate School of Comprehensive Human Sciences
      University of Tsukuba
      1-1-1 Tennodai
      Tsukuba
      Ibaraki
      Japan 305-8575
      Tel / Fax: +81 29 853 3071
      e-mail: tsuchiya-tky@umin.net
    Search for more papers by this author
  • M. Hasegawa,

    1. Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
    Search for more papers by this author
  • M. Fujimoto,

    1. Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
    Search for more papers by this author
  • K. Takehara,

    1. Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
    Search for more papers by this author
  • K. Tokunaga,

    1. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    Search for more papers by this author
  • S. Sato

    1. Department of Dermatology, Nagasaki University School of Medicine, Nagasaki, Japan
    Search for more papers by this author

Naoyuki Tsuchiya, MD, PhD
Doctoral Program in Social and Environmental Medicine
Graduate School of Comprehensive Human Sciences
University of Tsukuba
1-1-1 Tennodai
Tsukuba
Ibaraki
Japan 305-8575
Tel / Fax: +81 29 853 3071
e-mail: tsuchiya-tky@umin.net

Abstract

Activating and inhibitory signal transducers, CD19 and CD22, have been substantially implicated both in human systemic sclerosis (SSc) and tight-skin mouse, a model for SSc. We previously showed that a single nucleotide polymorphism (SNP) in CD19 promoter region was significantly associated with increased CD19 expression level and with susceptibility to SSc. In the present study, we examined whether CD22 polymorphisms were associated with susceptibility to SSc. CD22 variations were genotyped in 126 Japanese patients with SSc [47 diffuse cutaneous SSc and 79 limited cutaneous SSc (lcSSc)] and 93 unrelated healthy controls. At the c.2304C > A SNP coding for a synonymous substitution in exon 13, A/A genotype was observed in six patients with SSc (4.8 %) but none in the controls (P = 0.040). All six patients with A/A genotype belonged to the lcSSc subgroup (7.6%, P = 0.008 vs controls). Surface expression level of CD22 tended to be lower in B cells from the patients with A/A genotype (n = 5) as compared with C/A (n = 7) or C/C (n = 14) genotype (17% decrease, P = 0.0032). Taken together with our previous observation on CD19 polymorphism, intrinsic difference in the expression level of CD19 and CD22 was suggested to play a causative role in a proportion of patients with lcSSc.

Ancillary