Killer cell immunoglobulin‑like receptor alleles influence susceptibility to occult hepatitis B infection in West African population
Accepted: 12 April 2023
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Occult hepatitis B infection (OBI) is a public health problem in Burkina Faso. OBI represents a risk factor for the development of cirrhosis and hepatocellular carcinoma (HCC). OBI could be due to mutant viruses undetectable by HBsAg assays or a strong suppression of viral replication and gene expression under the pression of the host immune system. To investigate the role of killer cell immunoglobulin‑like receptor (KIR) gene polymorphisms in patients with OBI in Burkina Faso compared to healthy and chronic hepatitis B subjects. A total of 286 participants was recruited, including 42 cases of OBI, 110 cases of chronic hepatitis B and 134 HBV negative subjects. SSP‑PCR was performed to search for the presence of KIR genes. The HBV viral load was determined by qPCR. The frequencies of the activator gene KIR2DS5 (P=0.045) and the pseudogene KIR2DP1 (P<0.001) in patients with OBI were higher than those in patients with chronic hepatitis B. These genes are associated with susceptibility of occult hepatitis B infection. The frequencies of the inhibitory KIR gene KIR2DL3 (P=0.01) of patients with occult hepatitis B were lower than those in chronic hepatitis B patients. This gene KIR2DL3 is associated with protection against occult hepatitis B infection. Also, the frequencies of the inhibitory KIR genes KIR2DL2 (P<0.001), KIR2DL3 (P<0.001) and activators KIR2DS2 (P<0.001) in chronic hepatitis B patients were higher compared to the frequencies of the KIR genes in healthy subjects. These genes KIR2DL3, KIR2DL5 (A, B), KIR3DL3, KIR3DS1, KIR2DL2 and KIR2DS2 are thought to be genes associated with the susceptibility to OBI. The KIR2DS5 and KIR2DP1 genes could be associated with susceptibility to OBI. As for the KIR gene KIR2DL3 could be associated with protection against occult hepatitis B infection.
Raimondo G, Pollicino T, Cacciola I and Squadrito G: Occult hepatitis B virus infection. J Hepatol 46:160‑170, 2007.
Allain J and Candotti D: Diagnostic algorithm for HBV safe transfusion. Blood Transfus 7: 174‑182, 2009.
Feld J, Janssen HLA, Abbas Z, Elewaut A, Ferenci P, Isakov V, Khan AG, Lim SG, Locarnini SA, Ono SK, et al: World Gastroenterology Organisation Global Guideline Hepatitis B. J Clin Gastroenterol 50: 691‑703, 2016.
Pollicino T and Saitta C: Occult hepatitis B virus and hepatocellular carcinoma. World J Gastroenterol 20: 5951‑5961, 2014.
OMS. Hepatitis B [Internet]. pp1‑9, 2020. Available from: https://www.who.int/news‑room/fact‑sheets/detail/hepatitis‑b.
Somda KS, Sermé AK, Coulibaly A, Cissé K, Sawadogo A, Sombié AR and Bougouma A: Hepatitis B surface antigen should not be the only sought marker to distinguish blood donors towards Hepatitis B virus infection in high prevalence area. Open J Gastroenterol 6: 362‑372, 2016.
Diarra B, Yonli AT, Sorgho PA and Compaore TR: Occult Hepatitis B Virus infection and associated genotypes among HBsAg‑negative subjects in burkina faso. Mediterr J Hematol Infect Dis 10: 1‑9, 2018.
Vallet‑Pichard A and Pol S: L ’Hépatite B occulte. Virologie 12:87‑94, 2008.
Xu R, Zhang X, Zhang W, Fang Y, Zheng S and Yu X: Association of Human APOBEC3 cytidine deaminases with the generation of hepatitis Virus B x antigen mutants and hepatocellular carcinoma. Hepatology 46: 1810‑1820, 2007.
Vivekanandan P, Daniel HD, Kannangai R, Martinez‑murillo F and Torbenson M: Hepatitis B virus replication induces methylation of both host and viral DNA. J Virol 84: 4321‑4329, 2010.
Yindom LM, Mendy M, Bodimeade C, Chambion C, Aka P, Whittle HC, Rowland‑Jones SL and Walton R: KIR content genotypes associate with carriage of hepatitis B surface antigen, e antigen and HBV viral load in Gambians. PLoS One 12: e0188307, 2017.
Trowsdale J: Genetic and functional relationships between MHC and NK receptor Genes HLA class I and NK receptors are encoded within. Immunity 15: 363‑374, 2001.
Kulkarni S, Martin MP and Carrington M: The Ying and Yang of HLA and KIR in Human disease. Semin Immunol 20: 343‑352,2008.
Marsh SGE, Parham P, Dupont B, Geraghty DE, Trowsdale J, Middleton D, Vilches C, Carrington M, Witt C, Guethlein LA, et al: Killer‑cell immunoglobulin‑like receptor (KIR) nomenclature report, 2002. Immunogenetics 55: 220‑226, 2003.
Vilches C and Parham P: KIR: Diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol 20: 217‑251, 2002.
Robinson J, Halliwell JA, McWilliam H, Lopez R and Marsh SGE: IPD‑the immuno polymorphism database. Nucleic Acids Res 41: 1234‑1240, 2013.
González‑Galarza FF, Takeshita LYC, Santos EJM, Kempson F, Maia MHT, Da Silva AL, Teles e Silva AL, Ghattaoraya GS, Alfirevic A, Jones AR and Middleton D: Allele frequency net 2015 update: New features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res 43: D784‑D788, 2015.
Faure M and Long EO: KIR2DL4 (CD158d), an NK Cell‑activating receptor with inhibitory potential. J Immunol 4: 6208‑6214, 2002.
Uhrberg M, Parham P and Wernet P: Definition of gene content for nine common group B haplotypes of the Caucasoid population: KIR haplotypes contain between seven and eleven KIR genes. Immunogenetics 54: 221‑229, 2002.
Mcqueen KL, Dorighi KM, Guethlein LA, Wong R and Parham P: Donor‑recipient Combinations of Group A and B KIR haplotypes and HLA Class I ligand affect the outcome of HLA‑matched, sibling donor hematopoietic cell transplantation. Hum Immunol 68: 309‑323, 2007.
Ashouri E, Farjadian S, Reed EF, Ghaderi A and Rajalingam R: KIR gene content diversity in four Iranian populations. Immunogenetics 61: 483‑492, 2009.
Sorgho PA, Martinson JJ, Djigma FW, Yonli AT, Nagalo BM, Compaore TR, Obiri‑Yeboah D, Diarra B, Sombie HK, Zongo AW, et al: Insights into the interplay between KIR gene frequencies and chronic HBV infection in Burkina Faso. Mediterr J Hematol Infect Dis 10: e2018060, 2018.
Zhi‑Ming L, Yu‑Lian J, Zhao‑Lei F, Chun‑Xiao W, Zhen‑Fang D, Bing‑Chang Z and Yue‑Ran Z: Polymorphisms of killer cell immunoglobulin‑like receptor gene: Possible association with susceptibility to or clearance of hepatitis B virus infection in chinese han population. Croat Med J 48: 800‑807, 2007.
Kibar F, Ozturk OG, Ulu A, Erken E, Inal S, Dinkci S, Kurtaran B, Tasova Y, Aksu HS and Yaman A: Role of KIR genes and genotypes in susceptibility to or protection against hepatitis B virus infection in a Turkish cohort. Med Sci Monit 20: 28‑34, 2014.
Hu K: A practical approach to management of chronic hepatitis B. Int J Med Sci 2: 17‑23, 2005.
Miller SA, Dykes DD and Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16: 1, 1988.
Kulkarni S, Martin MP and Carrington M: KIR Genotyping by Multiplex PCR‑SSP. Methods Mol Biol 612: 365‑375, 2010.
WHO. Lignes directrices pour la prévention, les soins et le traitement en faveur des personnes atteintes d'une infection à hépatite B chronique [Internet]. pp176, 2015. Available from: http://apps.who.int/iris.
Simpore J, Savadogo A, Ilboudo D, Nadambega MC, Esposito M, Yara J, Pignatelli S, Pietra V and Musumeci S: Toxoplasma gondii, HCV, and HBV seroprevalence and co‑infection among HIV‑positive and ‑negative pregnant women in Burkina Faso. J Med Virol 78: 730‑733, 2006.
Tao I, Compaoré TR, Diarra B, Djigma F, Zohoncon TM, Assih M, Ouermi D, Pietra V, Karou SD and Simpore J: Seroepidemiology of hepatitis B and C viruses in the general population of burkina faso. Hepat Res Treat 2014: 781843, 2014.
Sanou AM, Benkirane K, Tinto B, Cissé A, Sagna T, Ilboudo AK, Dording C, Tarnagda Z, Muller CP and Hübschen JM: Prevalence of hepatitis B virus and hepatitis D virus coinfection in western burkina faso and molecular characterization of the detected virus strains. Int J Infect Dis 70: 15‑59, 2018.
INSD. Emploi et chômage: Enquête multisectorielle continue (EMC) [Internet]. 2014. Available from: www.insd.bf.
Carrington M and Norman P: The KIR Gene Cluster [Internet]. National Center for Biotechnology Information (US). pp227, 2003. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10135/
Delves PJ and Roitt IM: The immune system First of Two Parts. N Engl J Med 343: 37‑49, 2000.
Norman P, Carrington CVF, Byng M, Maxwell LD, Curran MD, Stephens HA, Chandanayingyong D, Verity DH, Hameed K, Ramdath DD and Vaughan RW: Natural killer cell immunoglobulin‑like receptor (KIR) locus profiles in African and South Asian populations. Genes Immun 3: 86‑95, 2002.
Parham P: Immunogenetics of killer‑cell immunoglobulin‑like receptors. Tissue Antigens 62: 194‑200, 2003.
Single RM, Martin MP, Gao X, Meyer D, Yeager M, Kidd JR, Kidd KK and Carrington M: Global diversity and evidence for coevolution of KIR and HLA. Nat Genet 39: 1114‑1119, 2007.
Lu Z, Zhang B, Chen S, Gai Z, Feng Z, Liu X, Liu Y, Wen X, Li L, Jiao Y, et al: Association of KIR genotypes and haplotypes with susceptibility to chronic hepatitis B virus infection in chinese han population. Cell Mol Immunol 5: 457‑463,2008.
Copyright (c) 2023 the Authors
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.