Association of polymorphisms in the mannose-binding lectin gene and pulmonary morbidity in preterm infants.
Deficiency in the collectin mannose-binding lectin (MBL) increases the risk for pulmonary and systemic infections and its complications in children and adults. The aim of this prospective cohort study was to determine the genetic association of sequence variations within the MBL gene with systemic infections and pulmonary short- and long-term complications in preterm infants below 32 weeks gestational age (GA). Three single-nucleotide polymorphisms (SNPs) in the coding region and one SNP in the promotor region of MBL2 were genotyped by direct sequencing and with sequence-specific probes in 284 newborn infants <32 weeks GA. Clinical variables were comprehensively monitored. An association was found between two SNPs and the development of bronchopulmonary dysplasia (BPD), defined as persistent oxygen requirement at 36 weeks postmenstrual age, adjusting for covariates GA, grade of respiratory distress syndrome and days on mechanical ventilation (rs1800450 (exon 1 at codon 54, B variant): odds ratio dominant model (OR)=3.59, 95% confidence interval (CI)=1.62-7.98; rs7096206 (-221, X variant): OR=2.40, 95% CI=1.16-4.96). Haplotype analyses confirmed the association to BPD, and a single haplotype (frequency 56%) including all SNPs in their wild-type form showed a negative association with the development of BPD. We detected no association between the MBL gene variations and the development of early-onset infections or further pulmonary complications. Frequent variants of the MBL gene, leading to low MBL concentrations, are associated with the diagnosis of BPD in preterm infants. This provides a basis for potential therapeutic options and further genetic and proteomic analysis of the function of MBL in the resistance against pulmonary long-term complications in preterm infants.
Hilgendorff
A
A
Department of Paediatrics, University of Giessen and Marburg, Giessen, Germany. anne.hilgendorff@med.uni-muenchen.de
Heidinger
K
K
Pfeiffer
A
A
Bohnert
A
A
König
I R
IR
Ziegler
A
A
Merz
C
C
Frey
G
G
Chakraborty
T
T
Gortner
L
L
Bein
G
G
D001997:Bronchopulmonary Dysplasia / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012127:Respiratory Distress Syndrome, Newborn / Q000453:epidemiology / Q000235:genetics; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000235:genetics
D037601:Mannose-Binding Lectin