TY - JOUR T1 - Joint effects of smoking during pregnancy and polymorphisms in the <em>MBL2</em> gene on cord blood levels of mannose-binding lectin JF - European Respiratory Journal JO - Eur Respir J VL - 40 IS - Suppl 56 SP - P2947 AU - Oliver Fuchs AU - Sven Michel AU - Luregn Jan Schlapbach AU - Sabina Gallati AU - Philipp Latzin AU - Michael Kabesch AU - Urs Frey Y1 - 2012/09/01 UR - http://erj.ersjournals.com/content/40/Suppl_56/P2947.abstract N2 - Smoking in pregnancy may affect the developing immune system and is associated with respiratory disease in the offspring. Also levels of mannose-binding lectin (MBL), a soluble innate immune mediator, are related to early respiratory morbidity. Yet, a joint effect of smoking in pregnancy and single-nucleotide polymorphisms (SNPs) in the MBL2 gene on MBL levels in cord blood (CB) is unknown.MBL was measured in CB in N=221 participants of a birth cohort of unselected, healthy, term infants and dichotomized using cutoffs of 700 and additionally of 300 ng/ml. We studied the association of smoking in pregnancy (validated by cotinine levels in the first urine) with MBL levels in CB. Using the Illumina® HumanOmniExpress chip for genotyping, we assessed the association of MBL2 SNPs and of SNPs on a genome-wide basis with MBL levels. We explored effect modification by smoking adjusting for multiple testing and confounders.Smoking in pregnancy was significantly associated with lower MBL levels for both cutoffs of 700 and 300 ng/ml with an OR (95% CI) of 3.30 (1.73;6.29) and 2.99 (1.43;6.28), respectively. Several MBL2 SNPs were significantly associated with decreased MBL levels (lowest p=1.08 x 10-15). On a genome-wide basis, no region other than MBL2 reached genome-wide significance. We found significant gene-environment interaction of MBL2 SNPs with smoking in pregnancy, such as for the downstream SNPs rs10824787 and rs3821968 (pint=0.036 and pint=0.044, respectively).Smoking during pregnancy lowers MBL levels in CB alone and in a joint effect with MBL2 SNPs. Our results may explain a link between genetic and environmental effects on early respiratory morbidity. ER -