TY - JOUR
T1 - Functional polymorphisms in the mannan-binding lectin 2 gene : Effect on MBL levels and otitis media
AU - Wiertsema, Selma
AU - Herpers, B.L.
AU - Veenhoven, R.H.
AU - Salimans, M.M.M.
AU - Ruven, H.J.T.
AU - Sanders, E.A.M.
AU - Rijkers, G.T.
PY - 2006
Y1 - 2006
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 mu g/mL compared with 0.70 mu g/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 derided 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.
AB - 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 mu g/mL compared with 0.70 mu g/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 derided 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.
U2 - 10.1016/j.jaci.2006.01.031
DO - 10.1016/j.jaci.2006.01.031
M3 - Article
C2 - 16750996
SN - 0091-6749
VL - 117
SP - 1344
EP - 1350
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 6
ER -