Association of transforming growth factor-beta1 gene polymorphism in the development of Epstein-Barr virus-related hematologic diseases.
OBJECTIVE
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.


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-1 beta 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)-beta1; the frequency of TGF-beta1 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).


CONCLUSIONS
Our results suggests that TGF-beta1 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.
Hatta
Kanako
K
Department of Pediatrics, Kyoto Prefectural University of Medicine, Kawaramachi, Hirokoji, Kamigyo-ku, Kyoto, Japan. mayi@iris.eonet.ne.jp
Morimoto
Akira
A
Ishii
Eiichi
E
Kimura
Hiroshi
H
Ueda
Ikuyo
I
Hibi
Shigeyoshi
S
Todo
Shinjiro
S
Sugimoto
Tohru
T
Imashuku
Shinsaku
S
D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003062:Codon; D016207:Cytokines / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D020022:Genetic Predisposition to Disease; D006402:Hematologic Diseases / Q000209:etiology* / Q000235:genetics / Q000821:virology; D006801:Humans; D007109:Immunity / Q000235:genetics; D007223:Infant; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D003062:Codon; D016207:Cytokines; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1