Haematologica, Vol 92, Issue 11, 1470-1474 doi:10.3324/haematol.11147
Copyright © 2007 by Ferrata Storti Foundation
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Malignant Lymphomas

Association of transforming growth factor-ß1 gene polymorphism in the development of Epstein-Barr virus-related hematologic diseases

Kanako Hatta, Akira Morimoto, Eiichi Ishii, Hiroshi Kimura, Ikuyo Ueda, Shigeyoshi Hibi, Shinjiro Todo, Tohru Sugimoto, Shinsaku Imashuku

From the Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan (KH, AM, IU, SH, ST, TS); Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime Japan (EI); Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan (HI); Division of Pediatrics, Takasago-Seibu Hospital, Takasago, Japan (SI)

Correspondence: Kanako Hatta, MD, Department of Pediatrics, Kyoto Prefectural University of Medicine, Kawaramachi, Hirokoji, Kamigyo-ku, Kyoto, Japan, 602-8566 E-mail: mayi{at}iris.eonet.ne.jp

Background and Objectives: Epstein-Barr virus (EBV) is etiologically associated with various hematologic disorders, including primary acute infectious mononucleosis (IM), hemophagocytic lymphohistiocytosis (EBV-HLH), chronic active EBV infection (CAEBV) and malignant lymphomas. Although cytokines play a central role in EBV-related immune responses, the exact mechanisms causing different clinical responses remain unclear. In this study, the pattern of cytokine gene polymorphisms was comparatively analyzed in EBV-related diseases.

Design and Methods: Eighty-nine patients with EBV-related disease were analyzed; 30 with IM, 28 with EBV-HLH and 31 with CAEBV. Eighty-one EBV-seropositive healthy adults were also used as controls. Associations with polymorphisms of various cytokines, including interleukin (IL)-1{alpha} and IL-1ß were evaluated. The gene polymorphisms were typed by polymerase chain reaction with sequence-specific primers.

Results: A significant difference of polymorphisms was found for transforming growth factor (TGF)-ß1; the frequency of TGF-ß1 codon 10 C allele was significantly higher in patients with EBV-related diseases than in controls (p<0.001). The difference was significant in patients with IM or HLH (p<0.001), but not in those with CAEBV (p=0.127), compared with controls. As regards other cytokines, the frequency of the IL-1{alpha} –889 C allele was significantly lower in patients with IM than in controls (p<0.05).

Interpretation and Conclusions: Our results suggests that TGF-ß1 codon 10 C allele plays a role in the development of EBV-related diseases and that the IL-1{alpha} –889 C allele may be involved in response failure and sequential progression into the development of HLH.

Key words: Epstein-Barr virus, cytokine gene polymorphism, IL-1, TGF-ß1.