TÜRKİYE POPÜLASYONUNDA HLA-DQ POLİMORFİZMLERİNİN HEPATİT B VİRÜS ENFEKSİYONU İLE İLİŞKİSİ

Year 2022, Volume: 5 Issue: 3, 186 - 192, 16.11.2022

Bülent Çakal , Muzaffer Arıkan , Alp Atasoy , Bilger Çavuş , Mehveş Poda , Mesut Bulakçı , Mine Güllüoğlu , Mehmet Demirci , Filiz Akyüz

https://doi.org/10.26650/JARHS2022-1142531

Abstract

Amaç Konak genetik faktörleri hepatit B virüs (HBV) enfeksiyonunun doğal seyri ve HBV ilişkili karaciğer hastalıklarının gelişme riski ile progresyonu üzerinde etkili olabilmektedir. Bu çalışmada HLA-DQ gen rs9272105, rs2856718 ve rs9275572 polimorfizmlerinin HBV doğal klirensi, viral yük ve HBV ile ilişkili karaciğer hasarı gelişimi ile ilişkisinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem Çalışmaya 150 kronik hepatit B (KHB) hastası ile kontrol grubu olarak 58’i kronik hepatit C (KHC) ve 82’si farklı klinik endikasyonlar nedeniyle karaciğer biyopsi işlemi gerçekleştirilen 140 hasta dâhil edildi. HLA-DQ rs9272105, rs2856718 ve rs9275572 genotip ve polimorfizmlerinin belirlenmesinde TaqMan SNP genotiplendirme yöntemi kullanıldı. Bulgular KHB’li ve kontrol grubundaki hastaların HLA-DQ gen rs9272105, rs2856718 ve rs9275572 genotip ve allel frekansları arasında farklılık tespit edildi (P<0,05). HLA-DQ rs9272105 AA genotip ve A allel varlığı, hepatit B yüzey antijen (Hepatitis B surface antigen; HBSAg) klirensi ve karaciğer hasarı ile ilişkiliydi (p<0,05). HLA-DQ gen rs2856718 ve rs9275572 ise HBV klirensi ve hastaların histolojik sonuçlarıyla ve ayrıca rs9272105 de dâhil hastaların viral yükleriyle ilişkili değildi. Sonuç HLA-DQ rs9272105 AA genotip ve A allel gerek HBV enfeksiyonunun kronikleşmesi gerekse HBV ilişkili karaciğer hasarının gelişmesi için risk faktördür.

Keywords

Hepatit B virüs, HLA-DQ, genetik polimorfizm, serokonversiyon, hastalık progresyonu, Hepatitis B Virus, genetic polymorphism, seroconversion, disease progression

Supporting Institution

Bu çalışma İstanbul Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından desteklenmiştir.

Project Number

TSA-2018-30611

Thanks

İstanbul Tıp Fakultesi Gastroenterohepatoloji Bilim Dalında gorevli Sayın Hemşire Nilay ARABACI ve Derya KAYA ile Radyoloji Biriminde görevli Sayın Hemşire Arzu ÖRENTEL’e bu projenin gerçekleştirilmesi aşamasındaki bilimsel duyarlılıkları, katkıları ve emeklerinden dolayı şükranlarımı sunarım.

ASSOCIATION OF HLA-DQ POLYMORPHISMS WITH HEPATITIS B VIRUS INFECTION IN TURKISH POPULATION

Abstract

Objective: Host genetic factors can affect the natural course of hepatitis B virus (HBV) infection and the risk of development and progression of HBV-related liver diseases. The aim of this study is to evaluate the role of the HLA-DQ gene polymorphisms rs9272105, rs2856718 and rs9275572 with HBV natural clearance, viral load and the development of HBV associated liver injury. Materials and Methods: The study included 150 patients with chronic hepatitis B (CHB) and 140 patients as the control group, 58 of whom had chronic hepatitis C (CHC) and 82 of whom had undergone a liver biopsy due to different clinical indications. The HLA-DQ gene rs9272105, rs2856718 and rs9275572 polymorphisms were genotypes in liver samples using the hybridization probe assay. Results: A difference was found between the HLA-DQ gene rs9272105, rs2856718 and rs9275572 genotype and allele frequencies of the patients with CHB and the control group (P<0,05). The HLA-DQ rs9272105 AA genotype and presence of A allele were associated with hepatitis B surface antigen (HBsAg) clearance and liver injury (p<0,05). In contrast, the HLA-DQ genes rs2856718 and rs9275572 were not associated with HBV clearance and patients’ histological outcomes, nor with patients’ viral load, including rs9272105. Conclusions: It has been suggested that the HLA-DQ rs9272105 AA genotype and the A allele are risk factors for both the persistence of HBV infection and the development of HBV-related liver damage. 

Keywords

Hepatitis B Virus, genetic polymorphism, seroconversion, disease progression

Project Number

TSA-2018-30611

References

• 1. Beasley RP. Hepatitis B virus: The major etiology of hepatocellular carcinoma. Cancer 1988;61:1942-56. google scholar
• 2. Dunn R, Wetten A, McPherson S, Donnelly MC. Viral hepatitis in 2021: The challenges remaining and how we should tackle them. World J Gastroenterol 2022; 7;28(1):76-951. google scholar
• 3. Xu J, Zhan Q, Fan Y, Yu Y, Zeng Z. Human genetic susceptibility to hepatitis B virus infection. Infection. Genetics and Evolution 2021;87:104663. doi: 10.1016/j.meegid.2020.104663. google scholar
• 4. Zhang Z, Wang C, Liu Z, Zou G, Li J, Lu M. Host Genetic Determinants of Hepatitis B Virus Infection. Front Genet 2019;10:696. google scholar
• 5. Zeng Z, Liu H, Xu H, Lu H, Yu Y, Xu X et al, HBV study consortium. Genome-wide association study identifies new loci associated with risk of HBV infection and disease progression. BMC Med Genomics 2021;14:84. google scholar
• 6. Graves AM, Virdis F, Morrison E, Âlvaro-Benito M, Khan AA, Freund C et al. Human hepatitis B viral infection outcomes are linked to naturally occurring variants of HLA-DOA that have altered function. J Immunol 2020 15;205(4):923-35. google scholar
• 7. Song Y, Xia T, Xia X, Zhang A-M. Genetic polymorphisms of the HLA-DP and HLA-DQ genes could influence Hepatitis B virus infection in Yunnan population. Immunol Invest 2021;50(1):47-57. google scholar
• 8. Xu T, Zhu A, Sun M, Lv J, Qian Z, Wang X, Wang T, Wang H, et al. Quantitative assessment of HLA-DQ gene polymorphisms with the development of hepatitis B virus infection, clearance, liver cirrhosis, and hepatocellular carcinoma. Oncotarget 2018; 9(1):96-109. google scholar
• 9. Lv J, Xu T, Qian Z, Wang H et al. Association between HLA-DQ Gene Polymorphisms and HBV-Related Hepatocellular Carcinoma. Gastroenterol Res Pract 2017;2017:7150386. doi:10.1155/2017/7150386. google scholar
• 10. Al-Qahtani A A, Al-Anazi MR, Abdo A A, Sanai FM, Al-Hamoudi W, Alswat KA, et al. Association between HLA variations and chronic hepatitis B virus infection in Saudi Arabian patients. PLoS ONE 2014;9(1):e80445. doi: 10.1371/journal.pone.0080445. google scholar
• 11. Xu T,Sun M, Wang H. Relationship between HLA-DQ Gene Polymorphism and Hepatitis B Virus Infection. Biomed Res Int 2017;2017:9679843. doi: 10.1155/2017/9679843. google scholar
• 12. Ishak K, Baptista A, Bianchi L, Calleo F, De Groote J, Gaudet F. Histological grading and staging of chronic hepatitis. J Hepatol 1995;22(6):696-9. google scholar
• 13. Kozuka R, Enomoto M, Sato-Matsubara M, Yoshida K, Motoyama H, Hagihara A, et al. Association between HLA-DQA1/DRB1 polymorphism and development of hepatocellular carcinoma during entecavir treatment. J Gastroenterol Hepatol 2019;34(5):937-46. google scholar
• 14. Wen J, Song C, Jiang D, Jin T, Dai J, Zhu L, et al. Hepatitis B virus genotype, mutations, human leukocyte antigen polymorphisms and their interactions in hepatocellular carcinoma: a multi-centre casecontrol study. Sci Rep 2015;16(5):16489. doi: 10.1038/ srep16489. google scholar
• 15. Li S, Qian J, Yang Y, Zhao W, Dai J, Bei J-X et al. GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers. PLoS Genet 2012;8:e1002791. doi: 10.1371/journal.pgen.1002791. google scholar
• 16. Hsieh AR, Fann CSJ, Lin HC, Tai J, Hsieh SY, Tai DI. Hepatitis B virus persistent infection-related single nucleotide polymorphisms in HLA regions are associated with viral load in hepatoma families. World J Gastroenterol 2021;27(37):6262-76. google scholar
• 17. Trinks J, Nishida N, Hulaniuk ML, Caputo M, Tsuchiura T, Marciano S, et al. Role of HLA-DP and HLA-DQ on the clearance of hepatitis B virus and the risk of chronic infection in a multiethnic population. Liver Int 2017;37(10):1476-87. google scholar
• 18. Zhang X, Jia J, Dong J, Yu F,Ma N,Li M, et al. HLA-DQ polymorphisms with HBV infection: different outcomes upon infection and prognosis to lamivudine therapy. J Viral Hepat 2014;21(7):491-8. google scholar
• 19. Mohammadi H, Alavian SM, Sharafi H. Association of single nucleotide polymorphisms in immune-related genes with spontaneous HBsAg seroconversion: A systematic review and meta-analysis. Int Immunopharmacology 2022;110:108982. doi: 10.1016/j.intimp.2022.108982. google scholar
• 20. Ochi Y, Hashimoto S, Kawabe N, Murao M, Nakano T, et al. HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection. Hepatol Res 2017;47(8):755-66. google scholar
• 21. Ji X, Zhang Q, Li B, Dua Y, Yin J, Liu W. Impacts of human leukocyte antigen DQ genetic polymorphisms and their interactions with hepatitis B virus mutations on the risks of viral persistence, liver cirrhosis, and hepatocellular carcinoma. Infect Genet Evol 2014;28:201-9. google scholar