Atypical Chemokine Receptor Polymorphism can not Affect Susceptibility to Hepatitis C Virus

Background: Hepatitis virus has infected 130 to150 million individuals globally. Atypical chemokinereceptor has become focus of research because ofits diverse roles in different diseases. However, little isknown regarding the association of atypical chemokinereceptor polymorphism with susceptibility to hepatitisvirus.Aims: To determine the association of an atypicalchemokine receptor polymorphism (rsl2075) withhepatitis virus susceptibility.Study Design: Case-control study.Methods: We collected blood samples from 231 patientsinfected with hepatitis virus and 239 blood donorsas control subjects. Genotyping of atypical chemokinereceptor was performed using '-nuclease assay withTaqMan-minor groove binding probes. Comparisonsbetween hepatitis virus-infected patients and controlsubjects were assessed using Fisher's exact test.Results: The genotype frequencies of *A/F *A,FY*A/FY*B and FY*B/FY*B were 86.1%, 13.9% and0% in the patient group, and 86.2%, 13.4% and 0.4% inthe control group, respectively. The difference in atypicalchemokine receptor genotype frequencies betweenhepatitis virus-infected patients and control groupwas not significant (p=1.00, OR=1.004, 95% CI=0.594-1.695). FY*A and FY*B allele frequencies were 93.1%and 6.9% in the patient group, and 92.9% and 7.1%in the control group, respectively. The difference inatypical chemokine receptor allele frequencies betweenhepatitis virus-infected patients and the control groupwas not significant (p=1.00, OR=0.972, 95% CI=0.589-1.603).Conclusion: Our result indicates that atypical chemokinereceptor polymorphism (rs12075) does not affectsusceptibility to hepatitis virus.

PDF

___

1. Williams R. Global challenges in liver disease. Hepatology 2006;44:521-6. 2. Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 2005;5:558-67.
3. Bowen DG, Walker CM. Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature 2005;436:946-52.
4. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology 2013;57:1333-42.
5. Chen YS, Li L, Cui FQ, Xing WG, Wang L, Jia ZY, et al. A seroepidemiological study on hepatitis C in China. Zhonghua Liu Xing Bing Xue Za Zhi 2011;32:888-91.
6. Davis MB, Walens A, Hire R, Mumin K, Brown AM, Ford D, et al. Distinct Transcript Isoforms of the Atypical Chemokine Receptor 1 (ACKR1) / Duffy Antigen Receptor for Chemokines (DARC) Gene Are Expressed in Lymphoblasts and Altered Isoform Levels Are Associated with Genetic Ancestry and the Duffy-Null Allele. PloS one 2015;10:e0140098.
7. Grimberg BT, Udomsangpetch R, Xainli J, McHenry A, Panichakul T, Sattabongkot J, et al. Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. PLoS Med 2007;4:e337.
8. Cotorruelo C, Biondi C, Racca L, Borras SG, Racca A. Duffy genotyping facilitates transfusion therapy. Clin Exp Med 2009;9:249-51.
9. de Carvalho GB. Duffy Blood Group System and the malaria adaptation process in humans. Rev Bras Hematol Hemoter 2011;33:55-64.
10. Iwamoto S, Li J, Sugimoto N, Okuda H, Kajii E. Characterization of the Duffy gene promoter: evidence for tissue-specific abolishment of expression in Fy(a-b-) of black individuals. Biochem Biophys Res Commun 1996;222:852-9.
11. Howes RE, Patil AP, Piel FB, Nyangiri OA, Kabaria CW, Gething PW, et al. The global distribution of the Duffy blood group. Nat Commun 2011;2:266.
12. Neote K, Mak JY, Kolakowski LF Jr, Schall TJ. Functional and biochemical analysis of the cloned Duffy antigen: identity with the red blood cell chemokine receptor. Blood 1994;84:44-52.
13. Darbonne WC, Rice GC, Mohler MA, Apple T, Hebert CA, Valente AJ, et al. Red blood cells are a sink for interleukin 8, a leukocyte chemotaxin. J Clin Invest 1991;88:1362-9.
14. King CL, Adams JH, Xianli J, Grimberg BT, McHenry AM, Greenberg LJ, et al. Fy(a)/Fy(b) antigen polymorphism in human erythrocyte Duffy antigen affects susceptibility to Plasmodium vivax malaria. Proc Natl Acad Sci USA 2011;108:20113-8.
15. Sippert EA, de Oliveira e Silva C, Visentainer JE, Sell AM. Association of duffy blood group gene polymorphisms with IL8 gene in chronic periodontitis. PloS one 2013;8:e83286.
16. Yang C, Yu KD, Xu WH, Chen AX, Fan L, Ou ZL, et al. Effect of genetic variants in two chemokine decoy receptor genes, DARC and CCBP2, on metastatic potential of breast cancer. PloS one 2013;8:e78901.
17. Kanto T, Hayashi N, Takehara T, Katayama K, Kato M, Akiyama M, et al. Low expression of erythrocyte complement receptor type 1 in chronic hepatitis C patients. J Med Virol 1996;50:126-34.
18. Miyaike J, Iwasaki Y, Takahashi A, Shimomura H, Taniguchi H, Koide N, et al. Regulation of circulating immune complexes by complement receptor type 1 on erythrocytes in chronic viral liver diseases. Gut 2002;51:591-6.
19. Ohi H, Tamano M, Okada N. Low CR1 (C3b receptor) level on erythrocytes is associated with poor prognosis in hemodialysis patients. Nephron Clin Pract 2008;108:23-7.
20. He W, Neil S, Kulkarni H, Wright E, Agan BK, Marconi VC, et al. Duffy antigen receptor for chemokines mediates trans-infection of HIV-1 from red blood cells to target cells and affects HIV-AIDS susceptibility. Cell Host Microbe 2008;4:52-62.
21. Ramsuran V, Kulkarni H, He W, Mlisana K, Wright EJ, Werner L, et al. Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women. Clin Infect Dis 2011;52:1248-56.
22. Cutbush M, Mollinson PL, Parkin DM. A new human blood group. Nature 1950;165:188-90.
23. Neote K, Darbonne W, Ogez J, Horuk R, Schall TJ. Identification of a promiscuous inflammatory peptide receptor on the surface of red blood cells. J Biol Chem 1993;268:12247-9.
24. Lettow I, Berres ML, Schmitz P, Müller T, Berg T, Neumann UP, et al. A Duffy antigen receptor for chemokines (DARC) polymorphism that determines pro-fibrotic chemokine serum concentrations is not directly associated with severity of hepatitis C infection. Hum Immunol 2011;72:273-7.
25. Kashiwazaki M, Tanaka T, Kanda H, Ebisuno Y, Izawa D, Fukuma N, et al. A high endothelial venule-expressing promiscuous chemokine receptor DARC can bind inflammatory, but not lymphoid, chemokines and is dispensable for lymphocyte homing under physiological conditions. Int Immunol 2003;15:1219-27.
26. Berres ML, Trautwein C, Schmeding M, Eurich D, Tacke F, Bahra M, et al. Serum chemokine CXC ligand 10 (CXCL10) predicts fibrosis progression after liver transplantation for hepatitis C infection. Hepatology 2011;53:596-603.
27. Palmer C, Corpuz T, Guirguis M, O'Toole S, Yan K, Bu Y, et al. The effect of obesity on intrahepatic cytokine and chemokine expression in chronic hepatitis C infection. Gut 2010;59:397-404.
28. Heydtmann M, Adams DH. Chemokines in the immunopathogenesis of hepatitis C infection. Hepatology 2009;49:676-88.
29. Comerford I, Milasta S, Morrow V, Milligan G, Nibbs R. The chemokine receptor CCX-CKR mediates effective scavenging of CCL19 in vitro. Eur J Immunol 2006;36:1904-16.
30. Schnabel RB, Baumert J, Barbalic M, Dupuis J, Ellinor PT, Durda P, et al. Duffy antigen receptor for chemokines (Darc) polymorphism regulates circulating concentrations of monocyte chemoattractant protein-1 and other inflammatory mediators. Blood 2010;115:5289-99.