Qian Cui, Yongxiang Zhang, Jing Su, Chao Shi, Na Lei, Keqin Ding, Jun Li, Rongbin Yu, Lu Wang, Ning Wang. The association between the genetic polymorphisms of LMP2/LMP7 and the outcomes of HCV infection among drug users[J]. The Journal of Biomedical Research, 2010, 24(5): 374-380. DOI: 10.1016/S1674-8301(10)60050-4
Citation:
Qian Cui, Yongxiang Zhang, Jing Su, Chao Shi, Na Lei, Keqin Ding, Jun Li, Rongbin Yu, Lu Wang, Ning Wang. The association between the genetic polymorphisms of LMP2/LMP7 and the outcomes of HCV infection among drug users[J]. The Journal of Biomedical Research, 2010, 24(5): 374-380. DOI: 10.1016/S1674-8301(10)60050-4
Qian Cui, Yongxiang Zhang, Jing Su, Chao Shi, Na Lei, Keqin Ding, Jun Li, Rongbin Yu, Lu Wang, Ning Wang. The association between the genetic polymorphisms of LMP2/LMP7 and the outcomes of HCV infection among drug users[J]. The Journal of Biomedical Research, 2010, 24(5): 374-380. DOI: 10.1016/S1674-8301(10)60050-4
Citation:
Qian Cui, Yongxiang Zhang, Jing Su, Chao Shi, Na Lei, Keqin Ding, Jun Li, Rongbin Yu, Lu Wang, Ning Wang. The association between the genetic polymorphisms of LMP2/LMP7 and the outcomes of HCV infection among drug users[J]. The Journal of Biomedical Research, 2010, 24(5): 374-380. DOI: 10.1016/S1674-8301(10)60050-4
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
2.
Department of Infectious Diseases, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Prov-ince, China
3.
Department of Epidemiology, National Center for AIDS/STD Control and Provention, Chinese Center for Disease Control and Prevention, Beijing 100050, China
Funds:
This study was supported by the National Mega-project of Science Research Project (No. 2008ZX10002-013 and No. 2009ZX1004-904)
Objective: To investigate a possible association of LMP2/LMP7 genes with chronic hepatitis C virus (HCV) infection, and to assess whether LMP2/LMP7 genes could influence the outcomes of HCV infection among drug users. Methods: Genomic DNAs of 362 anti-HCV sero-positive drug users and 225 control drug users were ex-tracted from the peripheral blood leukocytes. The sero-positive patients were divided into those who had persistent infection and those who had spontaneously cleared the infection. Polymorphisms of LMP genes were determined by PCR combined with restriction fragment length polymorphism (RFLP). Results: The distribution of LMP2 genotypes among the control, persistent infection and spontaneous clearance groups were not different. However, the LMP7 codon 145 Gln/Lys, Lys/Lys, and Gln/Lys+Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in control group (OR=1.75, 95%CI=1.06~2.90; OR=3.16, 95%CI=1.23-8.12; OR = 1.94, 95%CI=1.21-3.12, respectively). Similarly, the frequencies of the codon 145 Gln/Lys, Lys/Lys, and Gln/Lys+Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in the spontaneous clearance group (OR=1.64, 95%CI=1.04-2.57; OR=2.40, 95%CI=1.09-5.28; OR=1.76, 95%CI=1.15-2.69, respectively). Stratified analysis indicated that combined genotype Gln/Lys + Lys/Lys of the LMP7 gene was related to an increasing susceptibility to HCV infection (OR=1.91, 95%CI=1.02-3.55; OR=2.19, 95%CI=1.24-3.89; OR=1.91, 95%CI=1.05-3.48, OR=2.86, 95%CI=1.41-5.78, respectively) and the risk of persistent HCV infection (OR=1.94, 95%CI=1.12-3.34; OR=2.02, 95%CI=1.21-3.38; OR=1.78, 95%CI=1.12-2.85, OR=2.23, 95%CI=1.09-4.58, respectively) among > 30-year-old, males, the injection drug user (IDU) subjects and/or the shorter duration drug users (≤5 y). Conclusion: These results suggest that polymorphism of the LMP7 gene may have an influence on the outcomes of HCV infection, and is one of the factors accounting for the genetic sus-ceptibility to HCV infection among drug users.
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