Skip to main content
Erschienen in: Journal of Clinical Immunology 5/2008

01.09.2008

Mannose-binding Lectin MBL2 Gene Polymorphisms and Outcome of Hepatitis C Virus-infected Patients

verfasst von: Eirini Koutsounaki, George N. Goulielmos, Mary Koulentaki, Christianna Choulaki, Elias Kouroumalis, Emmanouil Galanakis

Erschienen in: Journal of Clinical Immunology | Ausgabe 5/2008

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Mannose-binding lectin (MBL) is involved in host’s response to several infections including hepatitis B but little is known about MBL and hepatitis C virus (HCV) infection. The present study attempts to investigate whether MBL2 genotype and serum MBL levels affect the course of HCV infection.

Results and Discussions

We investigated the variant alleles in MBL2 gene promoter and exon-1 regions in 80 Caucasian HCV-infected patients. Mutations in MBL2 were determined by polymerase chain reaction and restriction fragment length polymorphisms analysis. Serum MBL levels were measured by ELISA. Polymorphism homozygosity in exon-1 region was significantly related to lower serum MBL levels (p < 0.001), to liver inflammation (p = 0.034, OR = 11.7) and, in a lesser degree, to fibrosis. Polymorphisms in promoter sites −221nt and −550nt were not shown to be related with serum MBL levels or progress to liver inflammation and fibrosis. Serum MBL levels were adversely associated with progression to fibrosis (p = 0.037). Response to antiviral treatment was related to hepatitis C virus genotype (p < 0.001, OR = 10.9), but not to MBL2 genotype or serum MBL levels.

Conclusion

These findings suggest that polymorphisms in MBL2 gene exon-1 region are related to low serum MBL levels and progression of HCV infection to liver inflammation and fibrosis.
Literatur
1.
Zurück zum Zitat Dzwonek A, Novelli V, Bajaj-Elliott M, Turner M, Clapson M, Klein N. Mannose-binding lectin in susceptibility and progression of HIV-1 infection in children. Antivir Ther. 2006;11:499–505.PubMed Dzwonek A, Novelli V, Bajaj-Elliott M, Turner M, Clapson M, Klein N. Mannose-binding lectin in susceptibility and progression of HIV-1 infection in children. Antivir Ther. 2006;11:499–505.PubMed
2.
Zurück zum Zitat Garred P, Madsen HO, Balslev U, Hofmann B, Pedersen C, Gerstoft J, Svejgaard A. Susceptibility to HIV infection and progression of AIDS in relation to variant alleles of mannose-binding lectin. Lancet 1997;349:236–40.PubMedCrossRef Garred P, Madsen HO, Balslev U, Hofmann B, Pedersen C, Gerstoft J, Svejgaard A. Susceptibility to HIV infection and progression of AIDS in relation to variant alleles of mannose-binding lectin. Lancet 1997;349:236–40.PubMedCrossRef
3.
Zurück zum Zitat Ji X, Gewurz H, Spear GT. Mannose binding lectin (MBL) and HIV. Mol Immunol 2005;42:145–52.PubMedCrossRef Ji X, Gewurz H, Spear GT. Mannose binding lectin (MBL) and HIV. Mol Immunol 2005;42:145–52.PubMedCrossRef
4.
Zurück zum Zitat Brown KS, Ryder SD, Irving WL, Sim RB, Hickling TP. Mannan binding lectin and viral hepatitis. Immunol Lett. 2007;108:34–44.PubMedCrossRef Brown KS, Ryder SD, Irving WL, Sim RB, Hickling TP. Mannan binding lectin and viral hepatitis. Immunol Lett. 2007;108:34–44.PubMedCrossRef
5.
Zurück zum Zitat Ezekowitz A. Mannose-binding protein and susceptibility to chronic hepatitis B infection. Lancet. 1996;348:1396–7.PubMedCrossRef Ezekowitz A. Mannose-binding protein and susceptibility to chronic hepatitis B infection. Lancet. 1996;348:1396–7.PubMedCrossRef
6.
Zurück zum Zitat Worthley DL, Bardy PG, Gordon DL, Mullighan CG. Mannose-binding lectin and maladies of the bowel and liver. World J Gastroenterol. 2006;12:6420–8.PubMed Worthley DL, Bardy PG, Gordon DL, Mullighan CG. Mannose-binding lectin and maladies of the bowel and liver. World J Gastroenterol. 2006;12:6420–8.PubMed
7.
Zurück zum Zitat Bernig T, Breunis W, Brouwer N, Hutchinson A, Welch R, Roos D, Kuijpers T, et al. An analysis of genetic variation across the MBL2 locus in Dutch Caucasians indicates that 3′ haplotypes could modify circulating levels of mannose-binding lectin. Hum Genet. 2005;118:404–15.PubMedCrossRef Bernig T, Breunis W, Brouwer N, Hutchinson A, Welch R, Roos D, Kuijpers T, et al. An analysis of genetic variation across the MBL2 locus in Dutch Caucasians indicates that 3′ haplotypes could modify circulating levels of mannose-binding lectin. Hum Genet. 2005;118:404–15.PubMedCrossRef
8.
Zurück zum Zitat Larsen F, Madsen HO, Sim RB, Koch C, Garred P. Disease-associated mutations in human mannose-binding lectin compromise oligomerization and activity of the final protein. J Biol Chem. 2004;279:21302–11.PubMedCrossRef Larsen F, Madsen HO, Sim RB, Koch C, Garred P. Disease-associated mutations in human mannose-binding lectin compromise oligomerization and activity of the final protein. J Biol Chem. 2004;279:21302–11.PubMedCrossRef
9.
Zurück zum Zitat Thiel S, Frederiksen PD, Jensenius JC. Clinical manifestations of mannan-binding lectin deficiency. Mol Immunol. 2006;43:86–96.PubMedCrossRef Thiel S, Frederiksen PD, Jensenius JC. Clinical manifestations of mannan-binding lectin deficiency. Mol Immunol. 2006;43:86–96.PubMedCrossRef
10.
Zurück zum Zitat Ribeiro LZ, Tripp RA, Rossi LM, Palma PV, Yokosawa J, Mantese OC, Oliveira TF, Nepomuceno LL, Queiróz DA. Serum mannose-binding lectin levels are linked with respiratory syncytial virus (RSV) disease. J Clin Immunol. 2008;28:166–73PubMedCrossRef Ribeiro LZ, Tripp RA, Rossi LM, Palma PV, Yokosawa J, Mantese OC, Oliveira TF, Nepomuceno LL, Queiróz DA. Serum mannose-binding lectin levels are linked with respiratory syncytial virus (RSV) disease. J Clin Immunol. 2008;28:166–73PubMedCrossRef
11.
Zurück zum Zitat Chong WP, To YF, Ip WK, Yuen MF, Poon TP, Wong WH, Lai CL, et al. Mannose-binding lectin in chronic hepatitis B virus infection. Hepatology. 2005;42:1037–45.PubMedCrossRef Chong WP, To YF, Ip WK, Yuen MF, Poon TP, Wong WH, Lai CL, et al. Mannose-binding lectin in chronic hepatitis B virus infection. Hepatology. 2005;42:1037–45.PubMedCrossRef
12.
Zurück zum Zitat Hakozaki Y, Yoshiba M, Sekiyama K, Seike E, Iwamoto J, Mitani K, Mine M, et al. Mannose-binding lectin and the prognosis of fulminant hepatic failure caused by HBV infection. Liver 2002;22:29–34.PubMedCrossRef Hakozaki Y, Yoshiba M, Sekiyama K, Seike E, Iwamoto J, Mitani K, Mine M, et al. Mannose-binding lectin and the prognosis of fulminant hepatic failure caused by HBV infection. Liver 2002;22:29–34.PubMedCrossRef
13.
Zurück zum Zitat Song le H, Binh VQ, Duy DN, Juliger S, Bock TC, Luty AJ, Kremsner PG, et al. Mannose-binding lectin gene polymorphisms and hepatitis B virus infection in Vietnamese patients. Mutat Res 2003;522:119–25.PubMed Song le H, Binh VQ, Duy DN, Juliger S, Bock TC, Luty AJ, Kremsner PG, et al. Mannose-binding lectin gene polymorphisms and hepatitis B virus infection in Vietnamese patients. Mutat Res 2003;522:119–25.PubMed
14.
Zurück zum Zitat Thio CL, Mosbruger T, Astemborski J, Greer S, Kirk GD, O'Brien SJ, Thomas DL. Mannose binding lectin genotypes influence recovery from hepatitis B virus infection. J Virol. 2005;79:9192–6.PubMedCrossRef Thio CL, Mosbruger T, Astemborski J, Greer S, Kirk GD, O'Brien SJ, Thomas DL. Mannose binding lectin genotypes influence recovery from hepatitis B virus infection. J Virol. 2005;79:9192–6.PubMedCrossRef
15.
Zurück zum Zitat Yuen MF, Lau CS, Lau YL, Wong WM, Cheng CC, Lai CL. Mannose binding lectin gene mutations are associated with progression of liver disease in chronic hepatitis B infection. Hepatology. 1999;29:1248–51.PubMedCrossRef Yuen MF, Lau CS, Lau YL, Wong WM, Cheng CC, Lai CL. Mannose binding lectin gene mutations are associated with progression of liver disease in chronic hepatitis B infection. Hepatology. 1999;29:1248–51.PubMedCrossRef
16.
Zurück zum Zitat Bellamy R, Ruwende C, McAdam KP, Thursz M, Sumiya M, Summerfield J, Gilbert SC, et al. Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans. QJM 1998;91:13–8.PubMedCrossRef Bellamy R, Ruwende C, McAdam KP, Thursz M, Sumiya M, Summerfield J, Gilbert SC, et al. Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans. QJM 1998;91:13–8.PubMedCrossRef
17.
Zurück zum Zitat Cheong JY, Cho SW, Lim SK, Shin DH, Yoon SK, Lee JE, Hahm KB, et al. Lack of association between hepatitis B virus infection and polymorphism of mannose-binding lectin gene in Korean population. J Korean Med Sci 2005;20:65–9.PubMedCrossRef Cheong JY, Cho SW, Lim SK, Shin DH, Yoon SK, Lee JE, Hahm KB, et al. Lack of association between hepatitis B virus infection and polymorphism of mannose-binding lectin gene in Korean population. J Korean Med Sci 2005;20:65–9.PubMedCrossRef
18.
Zurück zum Zitat Hohler T, Wunschel M, Gerken G, Schneider PM, Meyer zum Buschenfelde KH, Rittner C. No association between mannose-binding lectin alleles and susceptibility to chronic hepatitis B virus infection in German patients. Exp Clin Immunogenet 1998;15:130–3.PubMedCrossRef Hohler T, Wunschel M, Gerken G, Schneider PM, Meyer zum Buschenfelde KH, Rittner C. No association between mannose-binding lectin alleles and susceptibility to chronic hepatitis B virus infection in German patients. Exp Clin Immunogenet 1998;15:130–3.PubMedCrossRef
19.
Zurück zum Zitat Matsushita M, Hijikata M, Ohta Y, Iwata K, Matsumoto M, Nakao K, Kanai K, et al. Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL. Arch Virol 1998;143:645–51.PubMedCrossRef Matsushita M, Hijikata M, Ohta Y, Iwata K, Matsumoto M, Nakao K, Kanai K, et al. Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL. Arch Virol 1998;143:645–51.PubMedCrossRef
20.
Zurück zum Zitat Matsushita M, Hijikata M, Matsushita M, Ohta Y, Mishiro S. Association of mannose-binding lectin gene haplotype LXPA and LYPB with interferon-resistant hepatitis C virus infection in Japanese patients. J Hepatol. 1998;29(5):695–700, Nov.PubMedCrossRef Matsushita M, Hijikata M, Matsushita M, Ohta Y, Mishiro S. Association of mannose-binding lectin gene haplotype LXPA and LYPB with interferon-resistant hepatitis C virus infection in Japanese patients. J Hepatol. 1998;29(5):695–700, Nov.PubMedCrossRef
21.
Zurück zum Zitat Sasaki K, Tsutsumi A, Wakamiya N, Ohtani K, Suzuki Y, Watanabe Y, Nakayama N, et al. Mannose-binding lectin polymorphisms in patients with hepatitis C virus infection. Scand J Gastroenterol. 2000;35:960–5.PubMedCrossRef Sasaki K, Tsutsumi A, Wakamiya N, Ohtani K, Suzuki Y, Watanabe Y, Nakayama N, et al. Mannose-binding lectin polymorphisms in patients with hepatitis C virus infection. Scand J Gastroenterol. 2000;35:960–5.PubMedCrossRef
22.
Zurück zum Zitat Kilpatrick DC, Delahooke TE, Koch C, Turner ML, Hayes PC. Mannan-binding lectin and hepatitis C infection. Clin Exp Immunol. 2003;132:92–5.PubMedCrossRef Kilpatrick DC, Delahooke TE, Koch C, Turner ML, Hayes PC. Mannan-binding lectin and hepatitis C infection. Clin Exp Immunol. 2003;132:92–5.PubMedCrossRef
23.
Zurück zum Zitat Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22(6):696–9, Jun.PubMedCrossRef Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22(6):696–9, Jun.PubMedCrossRef
24.
Zurück zum Zitat Tin SK, Lee LY, Thumboo J, Koh DR, Fong KY. PCR-RFLP genotyping for exon 1 and promoter region mutations of the human mannose binding lectin (MBL-2) gene. J Immunol Methods. 2005;303:148–51.PubMedCrossRef Tin SK, Lee LY, Thumboo J, Koh DR, Fong KY. PCR-RFLP genotyping for exon 1 and promoter region mutations of the human mannose binding lectin (MBL-2) gene. J Immunol Methods. 2005;303:148–51.PubMedCrossRef
25.
Zurück zum Zitat Summerfield JA, Ryder S, Sumiya M, Thursz M, Gorchein A, Monteil MA, Turner MW. Mannose binding protein gene mutations associated with unusual and severe infections in adults. Lancet. 1995;345:886–9.PubMedCrossRef Summerfield JA, Ryder S, Sumiya M, Thursz M, Gorchein A, Monteil MA, Turner MW. Mannose binding protein gene mutations associated with unusual and severe infections in adults. Lancet. 1995;345:886–9.PubMedCrossRef
26.
Zurück zum Zitat Summerfield JA, Sumiya M, Levin M, Turner MW. Association of mutations in mannose binding protein gene with childhood infection in consecutive hospital series. BMJ. 1997;314:1229–32.PubMed Summerfield JA, Sumiya M, Levin M, Turner MW. Association of mutations in mannose binding protein gene with childhood infection in consecutive hospital series. BMJ. 1997;314:1229–32.PubMed
27.
Zurück zum Zitat Vorup-Jensen T, Sorensen ES, Jensen UB, Schwaeble W, Kawasaki T, Ma Y, Uemura K, et al. Recombinant expression of human mannan-binding lectin. Int Immunopharmacol. 2001;1:677–87.PubMedCrossRef Vorup-Jensen T, Sorensen ES, Jensen UB, Schwaeble W, Kawasaki T, Ma Y, Uemura K, et al. Recombinant expression of human mannan-binding lectin. Int Immunopharmacol. 2001;1:677–87.PubMedCrossRef
28.
Zurück zum Zitat Thomas HC, Foster GR, Sumiya M, McIntosh D, Jack DL, Turner MW, Summerfield JA. Mutation of gene of mannose-binding protein associated with chronic hepatitis B viral infection. Lancet. 1996;348:1417–9.PubMedCrossRef Thomas HC, Foster GR, Sumiya M, McIntosh D, Jack DL, Turner MW, Summerfield JA. Mutation of gene of mannose-binding protein associated with chronic hepatitis B viral infection. Lancet. 1996;348:1417–9.PubMedCrossRef
29.
Zurück zum Zitat Brown KS, Keogh MJ, Tagiuri N, Grainge MJ, Presanis JS, Ryder SD, Irving WL, et al. Severe fibrosis in hepatitis C virus-infected patients is associated with increased activity of the mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex. Clin Exp Immunol. 2007;147:90–8.PubMed Brown KS, Keogh MJ, Tagiuri N, Grainge MJ, Presanis JS, Ryder SD, Irving WL, et al. Severe fibrosis in hepatitis C virus-infected patients is associated with increased activity of the mannan-binding lectin (MBL)/MBL-associated serine protease 1 (MASP-1) complex. Clin Exp Immunol. 2007;147:90–8.PubMed
30.
Zurück zum Zitat Minchinton RM, Dean MM, Clark TR, Heatley S, Mullighan CG. Analysis of the relationship between mannose-binding lectin (MBL) genotype, MBL levels and function in an Australian blood donor population. Scand J Immunol. 2002;56(6):630–41, Dec.PubMedCrossRef Minchinton RM, Dean MM, Clark TR, Heatley S, Mullighan CG. Analysis of the relationship between mannose-binding lectin (MBL) genotype, MBL levels and function in an Australian blood donor population. Scand J Immunol. 2002;56(6):630–41, Dec.PubMedCrossRef
Metadaten
Titel
Mannose-binding Lectin MBL2 Gene Polymorphisms and Outcome of Hepatitis C Virus-infected Patients
verfasst von
Eirini Koutsounaki
George N. Goulielmos
Mary Koulentaki
Christianna Choulaki
Elias Kouroumalis
Emmanouil Galanakis
Publikationsdatum
01.09.2008
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 5/2008
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-008-9201-8

Weitere Artikel der Ausgabe 5/2008

Journal of Clinical Immunology 5/2008 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.