Not polymorphism but methylation of class II transactivator gene promoter IV associated with persistent HBV infection.
BACKGROUND
Class II transactivator (CIITA) is the major rate-limiting regulator for expression of class II major histocompability complex (MHC-II). Human CIITA gene expression is controlled by four distinct promoters (pIto pIV).


OBJECTIVE
To evaluate the relationship among polymorphism and methylation status of CIITA gene promoters and persistent hepatitis B virus (HBV) infection.


METHODS
We recruited 21 patients with hepatocellular carcinoma (HCC), 45 liver cirrhosis (LC), 65 chronic hepatitis B (CHB), 26 acute hepatitis B (AHB) and 95 healthy blood donors. Polymorphism of CIITA gene promoters was assayed by PCR-SSCP-sequencing. Bioinformatics analysis was employed to predict the existence of CpG islands. Methylation-specific PCR (MSP) was used to detect the methylation status of CIITA gene pIV.


RESULTS
No sequence differences were observed at CIITA genes pI, III and IV among HCC, LC, CHB, AHB patients and healthy controls. No CpG islands were found in the pI, pII and pIII sequences, but there was a CpG island in pIV. The frequency of methylated POV was not significantly different within persistent HBV infection groups (patients with HCC, LC or CHB). Significance was found between the persistent infection group and acute HBV infection or healthy controls.


CONCLUSIONS
CIITA gene promoter sequences are conserved. PIV is highly methylated and associated with host susceptibility to HBV persistent infection.
He
Yingli
Y
Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
Zhao
YingRen
Y
Zhang
Shulin
S
Chen
Wei
W
Lin
ShuMei
S
Yang
Qian
Q
Liu
JinFeng
J
Yang
Yuan
Y
Jin
Yan
Y
Liu
Ming
M
D019175:DNA Methylation; D015967:Gene Expression Regulation, Viral; D005802:Genes, MHC Class II / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics*
C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators