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Functional polymorphisms in the mannan-binding lectin 2 gene: effect on MBL levels and otitis media.
J Allergy Clin Immunol. 2006 Jun; 117(6):1344-50.JA

Abstract

BACKGROUND

Mannan-binding lectin (MBL) can bind to microorganisms, initiating the lectin pathway of complement activation. Aberrant MBL serum levels, caused by MBL2 gene polymorphisms, are a possible risk factor for recurrent infections. Within the 7 common MBL haplotypes, still considerable variation in MBL serum levels exists.

OBJECTIVE

To investigate functional MBL levels and MBL2 polymorphisms in a large cohort of children with recurrent acute otitis media.

METHODS

Twelve genetic variants in the MBL2 gene and functional MBL serum levels were determined in a cohort of children with recurrent acute otitis media. Haplotypes were constructed and associated with functional MBL serum levels and the number of otitis episodes in the previous year.

RESULTS

The 7 common MBL2 haplotypes mainly determine the level of functional MBL in serum. In addition, the 3130G>C single nucleotide polymorphism, located in exon 4, further significantly influenced functional MBL levels within the LXPA haplotype. LXPA carriers with 3130G showed a significantly lower geometric mean functional MBL serum level of 0.19 mug/mL compared with 0.70 mug/mL in 3130C carriers (P = .026). Nonwild-type MBL2 carriers between 12 and 24 months had a significantly increased number of otitis episodes (5.1/y) compared with wild-type MBL2 carriers (4.1/y; P = .027). In older children, this association was not found anymore.

CONCLUSION

Additional single nucleotide polymorphisms within the 7 common haplotypes can further explain the observed variation in functional MBL serum levels. MBL seems to be of particular clinical importance during early childhood, when maternally derived antibodies have waned, and protective adaptive immunity is not well developed yet.

CLINICAL IMPLICATIONS

Single nucleotide polymorphisms in the promoter region, in exon 1, and in exon 4 of MBL2 contribute to increased risk for otitis media in children younger than 2 years.

Authors+Show Affiliations

Department of Pediatric Immunology, University Medical Center Utrecht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16750996

Citation

Wiertsema, Selma P., et al. "Functional Polymorphisms in the Mannan-binding Lectin 2 Gene: Effect On MBL Levels and Otitis Media." The Journal of Allergy and Clinical Immunology, vol. 117, no. 6, 2006, pp. 1344-50.
Wiertsema SP, Herpers BL, Veenhoven RH, et al. Functional polymorphisms in the mannan-binding lectin 2 gene: effect on MBL levels and otitis media. J Allergy Clin Immunol. 2006;117(6):1344-50.
Wiertsema, S. P., Herpers, B. L., Veenhoven, R. H., Salimans, M. M., Ruven, H. J., Sanders, E. A., & Rijkers, G. T. (2006). Functional polymorphisms in the mannan-binding lectin 2 gene: effect on MBL levels and otitis media. The Journal of Allergy and Clinical Immunology, 117(6), 1344-50.
Wiertsema SP, et al. Functional Polymorphisms in the Mannan-binding Lectin 2 Gene: Effect On MBL Levels and Otitis Media. J Allergy Clin Immunol. 2006;117(6):1344-50. PubMed PMID: 16750996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional polymorphisms in the mannan-binding lectin 2 gene: effect on MBL levels and otitis media. AU - Wiertsema,Selma P, AU - Herpers,Bjorn L, AU - Veenhoven,Reinier H, AU - Salimans,Marcel M M, AU - Ruven,Henk J T, AU - Sanders,Elisabeth A M, AU - Rijkers,Ger T, Y1 - 2006/04/27/ PY - 2005/09/13/received PY - 2005/12/19/revised PY - 2006/01/13/accepted PY - 2006/6/6/pubmed PY - 2006/7/20/medline PY - 2006/6/6/entrez SP - 1344 EP - 50 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 117 IS - 6 N2 - BACKGROUND: Mannan-binding lectin (MBL) can bind to microorganisms, initiating the lectin pathway of complement activation. Aberrant MBL serum levels, caused by MBL2 gene polymorphisms, are a possible risk factor for recurrent infections. Within the 7 common MBL haplotypes, still considerable variation in MBL serum levels exists. OBJECTIVE: To investigate functional MBL levels and MBL2 polymorphisms in a large cohort of children with recurrent acute otitis media. METHODS: Twelve genetic variants in the MBL2 gene and functional MBL serum levels were determined in a cohort of children with recurrent acute otitis media. Haplotypes were constructed and associated with functional MBL serum levels and the number of otitis episodes in the previous year. RESULTS: The 7 common MBL2 haplotypes mainly determine the level of functional MBL in serum. In addition, the 3130G>C single nucleotide polymorphism, located in exon 4, further significantly influenced functional MBL levels within the LXPA haplotype. LXPA carriers with 3130G showed a significantly lower geometric mean functional MBL serum level of 0.19 mug/mL compared with 0.70 mug/mL in 3130C carriers (P = .026). Nonwild-type MBL2 carriers between 12 and 24 months had a significantly increased number of otitis episodes (5.1/y) compared with wild-type MBL2 carriers (4.1/y; P = .027). In older children, this association was not found anymore. CONCLUSION: Additional single nucleotide polymorphisms within the 7 common haplotypes can further explain the observed variation in functional MBL serum levels. MBL seems to be of particular clinical importance during early childhood, when maternally derived antibodies have waned, and protective adaptive immunity is not well developed yet. CLINICAL IMPLICATIONS: Single nucleotide polymorphisms in the promoter region, in exon 1, and in exon 4 of MBL2 contribute to increased risk for otitis media in children younger than 2 years. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/16750996/Functional_polymorphisms_in_the_mannan_binding_lectin_2_gene:_effect_on_MBL_levels_and_otitis_media_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(06)00205-3 DB - PRIME DP - Unbound Medicine ER -