Advertisement

European Journal of Pediatrics

, Volume 168, Issue 11, pp 1305–1313 | Cite as

Mannose-binding lectin polymorphisms and recurrent respiratory tract infection in Chinese children

  • Jia Chen
  • Zhene Xu
  • Xi Ou
  • Mo Wang
  • Xiqiang Yang
  • Qiu LiEmail author
Original Paper

Abstract

In order to establish the reference value of mannose-binding lectin (MBL) serum level in children and to investigate the correlation between the polymorphisms of MBL2 gene and serum MBL level in healthy Chinese of Han ethnic group and in children of Chinese Han ethnic group with recurrent respiratory tract infections (RRTI), the concentration of oligomerized MBL was measured by enzyme-linked immunosorbent assay, and MBL2 gene polymorphisms were analyzed by restriction fragment length polymorphism of polymerase chain reaction and polymerase chain reaction-sequence specific primer. The median MBL levels in the 470 normal children were 2536 ng/ml, and the P2.5–P97.5 was 161–5,070 ng/ml. Our research showed that two promoter polymorphisms at −550, −221 of start codon and coding variants at codon 54 of MBL2 gene affected the protein level significantly and the most frequent genotype in Hans is HYPA/HYPA. Our results also showed that serum MBL level was significantly lower in recurrent respiratory tract infections patients compared with healthy controls (Z, −3.04, P = 0.002). The frequency of the promoter LXP haplotype and the B allele was significantly higher in RRTI patients than in controls (χ 2 4.05, P < 0.05; OR 1.63, 95%CI 1.01∼2.62; χ 2 4.27, P < 0.05; OR 1.94, 95%CI 1.02∼3.68). Conclusion: We have established that the reference value of serum MBL level in Chinese aged between 0 and 6 years (161–5,070 ng/ml), and we found that LXP and the B are risk factors for RRTI.

Keywords

Mannose-binding lectin Single nucleotide polymorphisms Recurrent respiratory tract infections 

Abbreviations

MBL

Mannose-binding lectin

PCR-SSP

Sequence-specific primed polymerase chain reaction

SNPs

Single nucleotide polymorphisms

RRTI

Recurrent respiratory tract infections

PCR-RFLP

Restriction fragment length polymorphism of polymerase chain reaction

ELISA

Enzyme-linked immunosorbent assay

Notes

Acknowledgments

We thank the children who participated, their parents for their co-operation and interest in the study, and the National Natural Scientific Foundation of China.

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work.

References

  1. 1.
    Baxter N, Sumiya M, Cheng S et al (2001) Recurrent miscarriage and variant alleles of mannose binding lectin, tumour necrosis factor and lymphotoxin alpha genes. Clin Exp Immunol 126(3):529–534 doi: 10.1046/j.1365-2249.2001.01663.x PubMedCrossRefGoogle Scholar
  2. 2.
    Bernig T, Boersma BJ, Howe TM (2006) The mannose-binding lectin (MBL2) haplotype and breast cancer: an association study in African-American and Caucasian women. Carcinogenesis 28(4):828–836 doi: 10.1093/carcin/bgl198 PubMedCrossRefGoogle Scholar
  3. 3.
    Collard CD, Vakeva A, Morrissey MA et al (2000) Complement activation after oxidative stress: role of the lectin complement pathway. Am J Pathol 156:1549–1556PubMedGoogle Scholar
  4. 4.
    Garred P, Madsen HO, Kurtzhals JA et al (1992) Diallelic polymorphism may explain variations of the blood concentration of mannan-binding protein in Eskimos, but not in black Africans. Eur J Immunogenet 19:403–412 doi: 10.1111/j.1744-313X.1992.tb00083.x PubMedCrossRefGoogle Scholar
  5. 5.
    Huang YF, Wang W, Han JY et al (2003) Increased frequency of the mannose-binding lectin LX haplotype in Chinese systemic lupus erythematosus patients. Eur J Immunogenet 30:121–124 doi: 10.1046/j.1365-2370.2003.00370.x PubMedCrossRefGoogle Scholar
  6. 6.
    Ip WK, Lau YL, Chan SY et al (2000) Mannose-binding lectin and rheumatoid arthritis in southern Chinese. Arthritis Rheum 43(8):1679–1687 doi: 10.1002/1529-0131(200008)43:8<1679::AID-ANR3>3.0.CO;2-D PubMedCrossRefGoogle Scholar
  7. 7.
    Ip WK, To YF, Cheng SK et al (2004) Serum mannose-binding lectin levels and mbl2 gene polymorphisms in different age and gender groups of southern Chinese adults. Scand J Immunol 59:310–314 doi: 10.1111/j.0300-9475.2004.01392.x PubMedCrossRefGoogle Scholar
  8. 8.
    Jordan JE, Montalto MC, Stahl GL (2001) Inhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury. Circulation 104:1413–1418 doi: 10.1161/hc3601.095578 PubMedCrossRefGoogle Scholar
  9. 9.
    Juliger S, Luckner D, Mordmuller B et al (2000) Promoter variants of the human mannose-binding lectin gene show different binding. Biochem Biophys Res Commun 275:617–622 doi: 10.1006/bbrc.2000.3343 PubMedCrossRefGoogle Scholar
  10. 10.
    Kilpatrick DC (2002) Mannan-binding lectin: clinical significance and applications. Biochim Biophys Acta 1572:401–413PubMedGoogle Scholar
  11. 11.
    Koch A, Melbye M, Sorensen P et al (2001) Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood. JAMA 285:1316–1321 doi: 10.1001/jama.285.10.1316 PubMedCrossRefGoogle Scholar
  12. 12.
    Koturoglu G, Onay H, Midilli R et al (2007) Evidence of an association between mannose binding lectin codon 54 polymorphism and adenoidectomy and/or tonsillectomy in children. Int J Pediatr Otorhinolaryngol 71(8):1157–1161 doi: 10.1016/j.ijporl.2007.05.004 PubMedCrossRefGoogle Scholar
  13. 13.
    Lee SG, Yum JS, Moon HM et al (2005) Analysis of mannose-binding lectin2 (MBL2) genotype and the serum protein levels in the Korean population. Mol Immunol 42:969–977 doi: 10.1016/j.molimm.2004.09.036 PubMedCrossRefGoogle Scholar
  14. 14.
    Madsen HO, Garred P, Thiel S et al (1995) Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol 155:3013–3020PubMedGoogle Scholar
  15. 15.
    Madsen HO, Satz ML, Hogh B et al (1998) Different molecular events result in low protein levels of mannan-binding lectin in populations from southeast Africa and South America. J Immunol 161:3169–3175PubMedGoogle Scholar
  16. 16.
    Matsushita M, Miyakawa H, Tanaka A et al (2001) Single nucleotide polymorphisms of the mannose-binding lectin are associated with susceptibility to primary biliary cirrhosis. J Autoimmun 17:251–257 doi: 10.1006/jaut.2001.0538 PubMedCrossRefGoogle Scholar
  17. 17.
    Megia A, Gallart L, Fernández-Real JM et al (2004) Mannose-binding lectin gene polymorphisms are associated with gestational diabetes mellitus. J Clin Endocrinol Metab 89(10):5081–5087 doi: 10.1210/jc.2004-0211 PubMedCrossRefGoogle Scholar
  18. 18.
    Milanese M, Segat L, De Seta F et al (2008) MBL2 genetic screening in patients with recurrent vaginal infections. Am J Reprod Immunol 59(2):146–151PubMedGoogle Scholar
  19. 19.
    Mullighan CG, Marshall SE, Welsh KI et al (2000) Mannose binding lectin polymorphisms are associated with early age of disease onset and autoimmunity in common variable immunodeficiency. Scand J Immunol 51(2):111–122 doi: 10.1046/j.1365-3083.2000.00697.x PubMedCrossRefGoogle Scholar
  20. 20.
    Ozbaş-Gerçeker F, Tezcan I, Berkel AI et al (2003) The effect of mannose-binding protein gene polymorphisms in recurrent respiratory system infections in children and lung tuberculosis. Turk J Pediatr 45(2):95–98PubMedGoogle Scholar
  21. 21.
    Pine SR, Mechanic LE, Ambs S, Harris CC et al (2007) Lung cancer survival and functional polymorphisms in MBL2, an innate-immunity gene. J Natl Cancer Inst 99(18):1401–1409 doi: 10.1093/jnci/djm128 PubMedCrossRefGoogle Scholar
  22. 22.
    Rantala A, Lajunen T, Juvonen R et al (2008) Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men. J Infect Dis 198(8):1247–1253 doi: 10.1086/591912 PubMedCrossRefGoogle Scholar
  23. 23.
    Rodriguez JA, Salgado GD, Saiz A (2004) MBL deficiency does not associate with recurrent pneumococcal infections in a group of Colombian children. J Trop Pediatr 50:379–380 doi: 10.1093/tropej/50.6.379 PubMedCrossRefGoogle Scholar
  24. 24.
    Santos IK, Costa CH, Krieger H et al (2001) Mannan-binding lectin enhances susceptibility to visceral leishmaniasis. Infect Immun 69:5212–5215 doi: 10.1128/IAI.69.8.5212-5215.2001 PubMedCrossRefGoogle Scholar
  25. 25.
    Schlapbach LJ, Aebi C, Otth M et al (2007) Serum levels of mannose-binding lectin and the risk of fever in neutropenia pediatric cancer patients. Pediatr Blood Cancer 49(1):11–16 doi: 10.1002/pbc.21097 PubMedCrossRefGoogle Scholar
  26. 26.
    Summerfield JA, Sumiya M, Levin M et al (1997) Association of mutations in mannose binding protein gene with childhood infection in consecutive hospital series. BMJ 314:1229–1232PubMedGoogle Scholar
  27. 27.
    Steffensen R, Thiel S, Varming K et al (2000) Detection of structural gene mutations and promoter polymorphisms in the mannan-binding lectin (MBL) gene by polymerase chain reaction with sequence-specific primers. J Immunol Methods 241:33–42 doi: 10.1016/S0022-1759(00)00198-8 PubMedCrossRefGoogle Scholar
  28. 28.
    Tang YW, Cleavinger PJ, Li H et al (2000) Analysis of candidate-host immunogenetic determinants in herpes simplex virus-associated Mollaret’s meningitis. Clin Infect Dis 30(1):176–178 doi: 10.1086/313616 PubMedCrossRefGoogle Scholar
  29. 29.
    Tuner MW (2003) The role of mannose-binding lectin in health and disease. Mol Immunol 40:423–429 doi: 10.1016/S0161-5890(03)00155-X CrossRefGoogle Scholar
  30. 30.
    Turner MW, Dinan L, Heatley S et al (2000) Restricted polymorphism of the mannose-binding lectin gene of indigenous Australians. Hum Mol Genet 9:1481–1486 doi: 10.1093/hmg/9.10.1481 PubMedCrossRefGoogle Scholar
  31. 31.
    Tuner MW, Hamvas RM (2000) Mannose-binding lectin: structure, function, genetics and disease associations. Rev Immunogenet 2:305–322Google Scholar
  32. 32.
    Valdimarsson H, Vikingsdottir T, Bang P et al (2004) Human plasma-derived mannose-binding lectin: a phase I safety and pharmacokinetic study. Scand J Immunol 59:97–102 doi: 10.1111/j.0300-9475.2004.01357.x PubMedCrossRefGoogle Scholar
  33. 33.
    Wiertsema SP, Herpers BL, Veenhoven RH et al (2006) Functional polymorphisms in the mannan-binding lectin 2 gene: effect on MBL levels and otitis media. J Allergy Clin Immunol 117(6):1344–1350 doi: 10.1016/j.jaci.2006.01.031 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Jia Chen
    • 1
  • Zhene Xu
    • 1
  • Xi Ou
    • 1
  • Mo Wang
    • 1
  • Xiqiang Yang
    • 1
  • Qiu Li
    • 1
    Email author
  1. 1.Department of Clinical Immunology, Children’s HospitalChongqing Medical UniversityChongqingChina

Personalised recommendations