Identification of novel variants in HLA class II region related to HLA DPB1 expression and disease progression in patients with chronic hepatitis C.
Recent genome-wide studies have demonstrated that HLA class II gene may play an important role in viral hepatitis. We studied genetic polymorphism and RNA expression of HLA class II genes in HCV-related liver diseases. The study was performed in groups consisting of 24 patients with HCV-related liver disease (12 of persistent normal ALT: PNALT group and 12 of advanced liver disease: ALD group) and 26 patients without HCV infection (control group). In PBMC samples, RNA expression of HLA class II genes (HLA-DPA1, DPB1, DQA1, DQB1, and DRB1) was analyzed by real-time RT-PCR. Furthermore, 22 single nucleotide polymorphisms (SNPs) in HLA class II gene and two SNPs in IL28B gene were genotyped by genetic analyzer (GENECUBE®). In expression analysis, only DPB1 level was significantly different. Mean expression level of DPB1gene in control group was 160.0, PNALT group 233.8, and ALD group 465.0 (P < 0.01). Of 24 SNPs, allele frequencies were statistically different in two SNPs (rs2071025 and rs3116996) between PNALT groups and ALD group (P < 0.01). In rs2071025, TT genotype was frequently detected in ALD group and expression level was significantly higher than the other genotypes (449.2 vs 312.9, P < 0.01). In rs3116996, TA or TT (non AA) genotype was frequently detected in ALD group and expression level was significantly higher than genotype AA (457.1 vs 220.9, P < 0.01). Genotyping and expression analysis in HLA class II gene revealed that two SNPs of HLA-DPB1 (rs2071025 and rs3116996) were significantly correlated to RNA expression and progression of HCV-related liver diseases.
Faculty of Medical Sciences, Second Department of Internal Medicine, University of Fukui, Fukui, Japan.
Katsushi
0000-0003-1377-8455
K
Hiramatsu
Faculty of Medical Sciences, Second Department of Internal Medicine, University of Fukui, Fukui, Japan.
Hidetaka
0000-0002-0860-1199
H
Matsuda
Faculty of Medical Sciences, Second Department of Internal Medicine, University of Fukui, Fukui, Japan.
Tomoyuki
T
Nemoto
Faculty of Medical Sciences, Second Department of Internal Medicine, University of Fukui, Fukui, Japan.
Takuto
T
Nosaka
Faculty of Medical Sciences, Second Department of Internal Medicine, University of Fukui, Fukui, Japan.
Yasushi
Y
Saito
Faculty of Medical Sciences, Second Department of Internal Medicine, University of Fukui, Fukui, Japan.
Tatsushi
T
Naito
Faculty of Medical Sciences, Second Department of Internal Medicine, University of Fukui, Fukui, Japan.
Kazuto
K
Takahashi
Faculty of Medical Sciences, Second Department of Internal Medicine, University of Fukui, Fukui, Japan.
Kazuya
K
Ofuji
Faculty of Medical Sciences, Second Department of Internal Medicine, University of Fukui, Fukui, Japan.
Masahiro
M
Ohtani
Faculty of Medical Sciences, Second Department of Internal Medicine, University of Fukui, Fukui, Japan.
Hiroyuki
H
Suto
Faculty of Medical Sciences, Division of Medical Genetics and Biochemistry, University of Fukui, Fukui, Japan.
Toshihiro
T
Yasuda
Faculty of Medical Sciences, Department of Clinical Laboratories, University of Fukui, Fukui, Japan.
Yukio
Y
Hida
Faculty of Medical Sciences, Department of Clinical Laboratories, University of Fukui, Fukui, Japan.
Hideki
H
Kimura
Tsuruga Institute of Biotechnology, Toyobo Co., Ltd., Osaka, Japan.
Yoshihiro
Y
Soya
Faculty of Medical Sciences, Second Department of Internal Medicine, University of Fukui, Fukui, Japan.
Yasunari
Y
Nakamoto
D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D005838:Genotype; D059868:HLA-DP beta-Chains / Q000096:biosynthesis* / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen
HCV; HLA-DPB1; HLA-class II; PNALT; SNPs