Functional polymorphisms in the mannan-binding lectin 2 gene: Effect on MBL levels and otitis media - 20/08/11
Reprint requests: Ger T. Rijkers, PhD, Department of Paediatric Immunology, Wilhelmina Children’s Hospital/University Medical Center Utrecht, Lundlaan 6, KC03.063.0, 3584 EA Utrecht, The Netherlands.Utrecht, Nieuwegein, Hoofddorp, and Amersfoort, The Netherlands
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 μg/mL compared with 0.70 μg/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.
Le texte complet de cet article est disponible en PDF.Key words : Mannan-binding lectin, complement, otitis media, functional mannan-binding lectin serum levels, polymorphisms, haplotypes
Abbreviations used : AOM, DGGE, MBL, OM, SNP, SSP-PCR
Plan
| Supported by The Netherlands Organization for Health Research and Development ZonMW (grant numbers 002828480 and 90461092) and the Netherlands Health Insurance Co Zilveren Kruis-Achmea. Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 117 - N° 6
P. 1344-1350 - juin 2006 Retour au numéro
Article précédent
- Spatial clustering of the IgE epitopes on the major timothy grass pollen allergen Phl p 1: Importance for allergenic activity
- Sabine Flicker, Peter Steinberger, Tanja Ball, Maria-Theresa Krauth, Petra Verdino, Peter Valent, Steve Almo, Rudolf Valenta
- The role of the mast cell in the pathophysiology of asthma
- Peter Bradding, Andrew F. Walls, Stephen T. Holgate
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?