BMC Research Notes | |
Association between single-nucleotide polymorphisms and early spontaneous hepatitis B virus e antigen seroconversion in children | |
Tomoo Fujisawa2  Tsuyoshi Sogo2  Tomoyuki Tsunoda2  Ayano Inui2  Jun Murakami1  Haruki Komatsu2  | |
[1] Division of Pediatrics and Perinatology, Faculty of Medicine, Tottori University, Yonago, Japan;Division of Hepatology and Gastroenterology, Department of Pediatrics, Eastern Yokohama Hospital, Yokohama, Japan | |
关键词: HLA-DP; Children; Seroconversion; HBeAg; IL10; IL28B; Human leukocyte antigen; Single-nucleotide polymorphism; Hepatitis B virus; | |
Others : 1125673 DOI : 10.1186/1756-0500-7-789 |
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received in 2014-06-16, accepted in 2014-10-24, 发布年份 2014 | |
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【 摘 要 】
Background
The disease progression following hepatitis B virus (HBV) infection is associated with single-nucleotide polymorphisms (SNPs). However, the role of SNPs in chronic HBV infection in children remains unclear. Here, we investigate the association between SNPs and early spontaneous hepatitis B e antigen (HBeAg) seroconversion in children with chronic hepatitis B infection.
Methods
This was a retrospective cohort study. We genotyped seven SNPs in the following genes, interleukin (IL)-10 (rs1800871 and rs1800872), human leukocyte antigen (HLA)-DPA1 (rs3077), HLA-DPB1 (rs9277535), HLA-DQB2 (rs7453920), HLA-DQB1 (rs2856718), and IL28B (rs8099917), in patients with chronic HBV infection using PCR and sequencing. These variants were analyzed for an association with early HBeAg seroconversion in children.
Results
Of 225 Japanese patients with chronic hepatitis B virus infection (male/female: 105/120, median age at initial visit: 6 years; range 0–44 years), 52 achieved spontaneous HBeAg seroconversion at the age of 10 years or younger (G1: early seroconversion group), and 57 did not achieve spontaneous HBeAg seroconversion under the age of 20 years (G2: late or no seroconversion group). Of the seven SNPs, only the HLA-DPA1 SNP displayed a low p-value (P = 0.070), but not significant, to have early HBeAg seroconversion in the dominant model and in the allele model (P = 0.073) using the chi-square test. The association study found a low p-value, but not significant, to have early HBeAg seroconversion in the dominant model for HLA-DPA1 (genotype TC + TT vs. CC, P = 0.070, odds ratio: 2.016, 95% confidence interval: 0.940-4.323) using a logistic regression model.
Conclusion
Although the HLA-DPA1 SNP did not show a statistically significant association with early HBeAg seroconversion in this study, the HLA-DPA1 SNP might increase the likelihood of achieving early spontaneous HBeAg seroconversion in children.
【 授权许可】
2014 Komatsu et al.; licensee BioMed Central Ltd.
【 预 览 】
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【 图 表 】
Figure 1.
【 参考文献 】
- [1]Kao JH, Chen DS: Global control of hepatitis B virus infection. Lancet Infect Dis 2002, 2:395-403.
- [2]Sokal EM, Paganelli M, Wirth S, Socha P, Vajro P, Lacaille F, Kelly D, Mieli-Vergani G: Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: consensus of an expert panel on behalf of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. J Hepatol 2013, 59:814-829.
- [3]El-Serag HB: Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012, 142:1264-1273 e1261.
- [4]Chu CM, Liaw YF: Chronic hepatitis B virus infection acquired in childhood: special emphasis on prognostic and therapeutic implication of delayed HBeAg seroconversion. J Viral Hepat 2007, 14:147-152.
- [5]Miyazoe S, Hamasaki K, Nakata K, Kajiya Y, Kitajima K, Nakao K, Daikoku M, Yatsuhashi H, Koga M, Yano M, Eguchi K: Influence of interleukin-10 gene promoter polymorphisms on disease progression in patients chronically infected with hepatitis B virus. Am J Gastroenterol 2002, 97:2086-2092.
- [6]Cheong JY, Cho SW, Hwang IL, Yoon SK, Lee JH, Park CS, Lee JE, Hahm KB, Kim JH: Association between chronic hepatitis B virus infection and interleukin-10, tumor necrosis factor-alpha gene promoter polymorphisms. J Gastroenterol Hepatol 2006, 21:1163-1169.
- [7]Du T, Guo XH, Zhu XL, Li JH, Lu LP, Gao JR, Gou CY, Li Z, Liu Y, Li H: Association of TNF-alpha promoter polymorphisms with the outcomes of hepatitis B virus infection in Chinese Han population. J Viral Hepat 2006, 13:618-624.
- [8]Wu JF, Wu TC, Chen CH, Ni YH, Chen HL, Hsu HY, Chang MH: Serum levels of interleukin-10 and interleukin-12 predict early, spontaneous hepatitis B virus e antigen seroconversion. Gastroenterology 2010, 138:165-172 e161-163.
- [9]Wu JF, Ni YH, Lin YT, Lee TJ, Hsu SH, Chen HL, Tsuei DJ, Hsu HY, Chang MH: Human interleukin-10 genotypes are associated with different precore/core gene mutation patterns in children with chronic hepatitis B virus infection. J Pediatr 2011, 158:808-813.
- [10]Xia Q, Zhou L, Liu D, Chen Z, Chen F: Relationship between TNF- < alpha > gene promoter polymorphisms and outcomes of hepatitis B virus infections: a meta-analysis. PLoS One 2011, 6:e19606.
- [11]Chatzidaki V, Kouroumalis E, Galanakis E: Hepatitis B virus acquisition and pathogenesis in childhood: host genetic determinants. J Pediatr Gastroenterol Nutr 2011, 52:3-8.
- [12]Kamatani Y, Wattanapokayakit S, Ochi H, Kawaguchi T, Takahashi A, Hosono N, Kubo M, Tsunoda T, Kamatani N, Kumada H, Puseenam A, Sura T, Daigo Y, Chayama K, Chantratita W, Nakamura Y, Matsuda K: A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nat Genet 2009, 41:591-595.
- [13]Mbarek H, Ochi H, Urabe Y, Kumar V, Kubo M, Hosono N, Takahashi A, Kamatani Y, Miki D, Abe H, Tsunoda T, Kamatani N, Chayama K, Nakamura Y, Matsuda K: A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population. Hum Mol Genet 2011, 20:3884-3892.
- [14]Guo X, Zhang Y, Li J, Ma J, Wei Z, Tan W, O'Brien SJ: Strong influence of human leukocyte antigen (HLA)-DP gene variants on development of persistent chronic hepatitis B virus carriers in the Han Chinese population. Hepatology 2011, 53:422-428.
- [15]Wang L, Wu XP, Zhang W, Zhu DH, Wang Y, Li YP, Tian Y, Li RC, Li Z, Zhu X, Li JH, Cai J, Liu L, Miao XP, Liu Y, Li H: Evaluation of genetic susceptibility loci for chronic hepatitis B in Chinese: two independent case–control studies. PLoS One 2011, 6:e17608.
- [16]Li J, Yang D, He Y, Wang M, Wen Z, Liu L, Yao J, Matsuda K, Nakamura Y, Yu J, Jiang X, Sun S, Liu Q, Jiang X, Song Q, Chen M, Yang H, Tang F, Hu X, Wang J, Chang Y, He X, Chen Y, Lin J: Associations of HLA-DP variants with hepatitis B virus infection in southern and northern Han Chinese populations: a multicenter case–control study. PLoS One 2011, 6:e24221.
- [17]Hu L, Zhai X, Liu J, Chu M, Pan S, Jiang J, Zhang Y, Wang H, Chen J, Shen H, Hu Z: Genetic variants in human leukocyte antigen/DP-DQ influence both hepatitis B virus clearance and hepatocellular carcinoma development. Hepatology 2012, 55:1426-1431.
- [18]Nishida N, Sawai H, Matsuura K, Sugiyama M, Ahn SH, Park JY, Hige S, Kang JH, Suzuki K, Kurosaki M, Asahina Y, Mochida S, Watanabe M, Tanaka E, Honda M, Kaneko S, Orito E, Itoh Y, Mita E, Tamori A, Murawaki Y, Hiasa Y, Sakaida I, Korenaga M, Hino K, Ide T, Kawashima M, Mawatari Y, Sageshima M, Ogasawara Y, et al.: Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean. PLoS One 2012, 7:e39175.
- [19]Wong DK, Watanabe T, Tanaka Y, Seto WK, Lee CK, Fung J, Lin CK, Huang FY, Lai CL, Yuen MF: Role of HLA-DP polymorphisms on chronicity and disease activity of hepatitis B infection in Southern Chinese. PLoS One 2013, 8:e66920.
- [20]An P, Winkler C, Guan L, O'Brien SJ, Zeng Z: A common HLA-DPA1 variant is a major determinant of hepatitis B virus clearance in Han Chinese. J Infect Dis 2011, 203:943-947.
- [21]Cheng HR, Liu CJ, Tseng TC, Su TH, Yang HI, Chen CJ, Kao JH: Host genetic factors affecting spontaneous HBsAg seroclearance in chronic hepatitis B patients. PLoS One 2013, 8:e53008.
- [22]Sasieni PD: From genotypes to genes: doubling the sample size. Biometrics 1997, 53:1253-1261.
- [23]Faul F, Erdfelder E, Lang AG, Buchner A: G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007, 39:175-191.
- [24]Kotlowski R, Bernstein CN, Silverberg MS, Krause DO: Population-based case–control study of alpha 1-antitrypsin and SLC11A1 in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2008, 14:1112-1117.
- [25]Hu Z, Liu Y, Zhai X, Dai J, Jin G, Wang L, Zhu L, Yang Y, Liu J, Chu M, Wen J, Xie K, Du G, Wang Q, Zhou Y, Cao M, Liu L, He Y, Wang Y, Zhou G, Jia W, Lu J, Li S, Liu J, Yang H, Shi Y, Zhou W, Shen H: New loci associated with chronic hepatitis B virus infection in Han Chinese. Nat Genet 2013, 45:1499-1503.
- [26]Seto WK, Wong DK, Kopaniszen M, Proitsi P, Sham PC, Hung IF, Fung J, Lai CL, Yuen MF: HLA-DP and IL28B polymorphisms: influence of host genome on hepatitis B surface antigen seroclearance in chronic hepatitis B. Clin Infect Dis 2013, 56:1695-1703.
- [27]Singh R, Kaul R, Kaul A, Khan K: A comparative review of HLA associations with hepatitis B and C viral infections across global populations. World J Gastroenterol 2007, 13:1770-1787.
- [28]Liu HY, Kong BH, Luo X, Xu YP, Dai MS, Jiang S: Study on the association between maternal-infantile vertical transmission of hepatitis B virus and human leukocyte antigen DR gene domain. Zhonghua Fu Chan Ke Za Zhi 2003, 38:599-603.
- [29]Xu YY, Yu JY, Zhong YW, Song HB, Liu HH, Jia LL, Li SL, Xu JQ, Li Q: Association between the frequency of class II HLA antigens and the susceptibility to intrauterine infection of hepatitis B virus. Int J Biol Sci 2008, 4:111-115.
- [30]Hohler T, Reuss E, Evers N, Dietrich E, Rittner C, Freitag CM, Vollmar J, Schneider PM, Fimmers R: Differential genetic determination of immune responsiveness to hepatitis B surface antigen and to hepatitis A virus: a vaccination study in twins. Lancet 2002, 360:991-995.
- [31]Martinetti M, De Silvestri A, Belloni C, Pasi A, Tinelli C, Pistorio A, Salvaneschi L, Rondini G, Avanzini MA, Cuccia M: Humoral response to recombinant hepatitis B virus vaccine at birth: role of HLA and beyond. Clin Immunol 2000, 97:234-240.
- [32]Wu JF, Chen CH, Hsieh RP, Shih HH, Chen YH, Li CR, Chiang CY, Shau WY, Ni YH, Chen HL, Hsu HY, Chang MH: HLA typing associated with hepatitis B E antigen seroconversion in children with chronic hepatitis B virus infection: a long-term prospective sibling cohort study in Taiwan. J Pediatr 2006, 148:647-651.
- [33]Edwards JA, Durant BM, Jones DB, Evans PR, Smith JL: Differential expression of HLA class II antigens in fetal human spleen: relationship of HLA-DP, DQ, and DR to immunoglobulin expression. J Immunol 1986, 137:490-497.
- [34]Guardiola J, Maffei A: Control of MHC class II gene expression in autoimmune, infectious, and neoplastic diseases. Crit Rev Immunol 1993, 13:247-268.
- [35]Zino E, Frumento G, Marktel S, Sormani MP, Ficara F, Di Terlizzi S, Parodi AM, Sergeant R, Martinetti M, Bontadini A, Bonifazi F, Lisini D, Mazzi B, Rossini S, Servida P, Ciceri F, Bonini C, Lanino E, Bandini G, Locatelli F, Apperley J, Bacigalupo A, Ferrara GB, Bordignon C, Fleischhauer K: A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation. Blood 2004, 103:1417-1424.
- [36]Shaw BE, Potter MN, Mayor NP, Pay AL, Smith C, Goldman JM, Prentice HG, Marsh SG, Madrigal JA: The degree of matching at HLA-DPB1 predicts for acute graft-versus-host disease and disease relapse following haematopoietic stem cell transplantation. Bone Marrow Transplant 2003, 31:1001-1008.
- [37]Fleischhauer K, Shaw BE, Gooley T, Malkki M, Bardy P, Bignon JD, Dubois V, Horowitz MM, Madrigal JA, Morishima Y, Oudshoorn M, Ringden O, Spellman S, Velardi A, Zino E, Petersdorf EW, International Histocompatibility Working Group in Hematopoietic Cell Transplantation: Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study. Lancet Oncol 2012, 13:366-374.
- [38]Singh P, Colombe BW, Francos GC, Martinez Cantarin MP, Frank AM: Acute humoral rejection in a zero mismatch deceased donor renal transplant due to an antibody to an HLA-DP alpha. Transplantation 2010, 90:220-221.
- [39]Thaunat O, Hanf W, Dubois V, McGregor B, Perrat G, Chauvet C, Touraine JL, Morelon E: Chronic humoral rejection mediated by anti-HLA-DP alloantibodies: insights into the role of epitope sharing in donor-specific and non-donor specific alloantibodies generation. Transpl Immunol 2009, 20:209-211.
- [40]Hollenbach JA, Thompson SD, Bugawan TL, Ryan M, Sudman M, Marion M, Langefeld CD, Thomson G, Erlich HA, Glass DN: Juvenile idiopathic arthritis and HLA class I and class II interactions and age-at-onset effects. Arthritis Rheum 2010, 62:1781-1791.
- [41]Fontenot AP, Torres M, Marshall WH, Newman LS, Kotzin BL: Beryllium presentation to CD4+ T cells underlies disease-susceptibility HLA-DP alleles in chronic beryllium disease. Proc Natl Acad Sci U S A 2000, 97:12717-12722.
- [42]Lombardi G, Germain C, Uren J, Fiorillo MT, du Bois RM, Jones-Williams W, Saltini C, Sorrentino R, Lechler R: HLA-DP allele-specific T cell responses to beryllium account for DP-associated susceptibility to chronic beryllium disease. J Immunol 2001, 166:3549-3555.
- [43]O'Brien TR, Kohaar I, Pfeiffer RM, Maeder D, Yeager M, Schadt EE, Prokunina-Olsson L: Risk alleles for chronic hepatitis B are associated with decreased mRNA expression of HLA-DPA1 and HLA-DPB1 in normal human liver. Genes Immunol 2011, 12:428-433.
- [44]Lotsch J: Basic genetic statistics are necessary in studies of functional associations in anesthesiology. Anesthesiology 2007, 107:168-169. author reply 169
- [45]Vermehren J, Lotsch J, Susser S, Wicker S, Berger A, Zeuzem S, Sarrazin C, Doehring A: A common HLA-DPA1 variant is associated with hepatitis B virus infection but fails to distinguish active from inactive Caucasian carriers. PLoS One 2012, 7:e32605.
- [46]Chang MH, Sung JL, Lee CY, Chen CJ, Chen JS, Hsu HY, Lee PI, Chen DS: Factors affecting clearance of hepatitis B e antigen in hepatitis B surface antigen carrier children. J Pediatr 1989, 115:385-390.
- [47]Kim HS, Kim HJ, Shin WG, Kim KH, Lee JH, Kim HY, Jang MK: Predictive factors for early HBeAg seroconversion in acute exacerbation of patients with HBeAg-positive chronic hepatitis B. Gastroenterology 2009, 136:505-512.