[The role of DNA methylation in the pathogenesis of adult idiopathic thrombocytopenic purpura].
OBJECTIVE
To explore the role of DNA methylation in pathogenesis of adult idiopathic thrombocytopenic purpura (ITP).


METHODS
We measured DNA methyltransferases (DNMTs) 1, 3A and 3B mRNA expression in peripheral blood mononuclear cells of 48 adult ITP patients and 36 normal controls using real-time polymerase chain reaction, as well as the plasma levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) with reversed phase high performance liquid chromatography (HPLC). Furthermore, we determined the expression of CD(11a)/LFA-1 on CD(4)(+) or CD(8)(+) T cells by three-color flow cytometry.


RESULTS
The mRNA expression of two DNA methyltransferases (DNMT3A and DNMT3B) was significantly lower when comparing ITP patients with healthy controls (P < 0.01). Although there were decreased tendency when comparing expression of DNMT1 of ITP patients with healthy controls, no significant differences were found (P > 0.05). The SAH concentration in the plasma of ITP patients was significantly elevated than that in the healthy controls (P < 0.05). However we found significant differences of SAM and SAM/SAH ratio in the plasma of ITP patients when compared with the healthy subjects (both P > 0.05). In addition, CD(11a)/LFA-1 expression on CD(8)(+) T lymphocytes increased in ITP patients compared with the control group (P < 0.01), whereas CD(11a)/LFA-1 expression on CD(4)(+) T lymphocytes and CD(4)(+)CD(11a)(+)/CD(8)(+)CD(11a)(+) ratio was significantly decreased in ITP patients than that in control group (both P < 0.01).


CONCLUSIONS
Aberrant DNA methylation in peripheral blood and CD(11a)/LFA-1 expression on T cell surface may play an important role in the pathogenesis of ITP, although the underlying mechanisms still await further investigation.
Tao
Jie
J
Department of Hematology, The First Hospital of Shanxi Medical University, Taiyuan 030001, China. sxtaojie@yahoo.com.cn
Yang
Ming
M
Chen
Zhong
Z
Zhang
Wei-Hua
WH
Zhang
Xiu-Lian
XL
Yang
Ren-Chi
RC
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood*; D012333:RNA, Messenger / Q000235:genetics; D012435:S-Adenosylhomocysteine / Q000097:blood; D012436:S-Adenosylmethionine / Q000097:blood; D013601:T-Lymphocytes / Q000378:metabolism*; D055815:Young Adult
D012333:RNA, Messenger; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D004248:DNA (Cytosine-5-)-Methyltransferases