Mannose-binding lectin in term newborns and their mothers: Genotypic and phenotypic relationship (original) (raw)
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Journal of …, 2011
The aim of this study was to determine the serum mannosebinding lectin (MBL) levels and the frequency of MBL gene polymorphisms in infants with neonatal sepsis. Study Design: Between January 2008 and January 2010, a total of 93 infants were included in this study and 53 of them had neonatal sepsis diagnosis as study group and 40 infants who had no sepsis according to clinical and laboratory findings as control group. Result: Serum MBL levels were found to be low in 17 of 93 infants. Eleven of them were in the sepsis group and six of them were in the control group. Serum MBL levels were significantly lower in infants with sepsis compared with the control group. Frequencies of genotype AB and BB were also significantly higher in the study group compared with the control group. Most importantly, presence of B allele of MBL exon 1 gene was found to be associated with an increased risk for neonatal sepsis. Additionally, in the study group, the mean serum MBL levels were found to be significantly lower in the premature infants compared with the term infants. Pneumonia, bronchopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH) were significantly higher in infants with MBL deficiency compared with infants with normal MBL levels. Conclusion: Low MBL levels and presence of B allele of MBL exon 1 gene were found to be important risk factors for development of both neonatal sepsis and pneumonia, especially in premature infants. Low MBL levels and MBL gene polymorphisms might also be associated with inflammation-related neonatal morbidities such as BPD and IVH.
Genetics in Medicine, 2006
Human mannose-binding lectin, encoded by the MBL2 gene, is an important component of innate immunity and an important regulator of inflammatory processes. MBL2 gene polymorphisms are associated with an increased risk of neonatal infections and some data suggest a relation between the maternal MBL2 genotype and the risk of premature delivery. In this study, we evaluated whether there is an association between the fetal MBL2 genotype and prematurity. Methods: A microarray-based on-chip PCR method was used to simultaneously detect five common MBL2 polymorphisms (codon 52, 54, 57; promoter-550,-221) in 204 DNA samples isolated from archival blood cards. MBL2 genotypes of infants born before the 36 th week of pregnancy (N ϭ 102) were compared to a control group of infants born at term after the 37 th week (N ϭ 102). Results: The frequency of the codon 52 polymorphism was significantly higher in the pre-term group compared to the term group (10.8% versus 4.9%, P ϭ 0.04), while the frequency of the codon 54 polymorphism was equal in both groups (11.3% versus 11.8%). Interestingly, carriers of genotypes (O/O) likely conferring deficient MBL plasma levels were more common in the group of premature birth (9.8% versus 2.9%, P ϭ 0.05), while the promoter-550 C/C genotype was underrepresented in the pre-term birth group (24.5% versus 39.2%, P ϭ 0.03). Conclusion: Our data add to the knowledge about genetic predisposition to prematurity and suggest that the fetal MBL2 genotype might be an additional genetic factor contributing to the risk of premature delivery.
Journal of pediatric genetics, 2018
Background Mannose-binding lectin (MBL) is a component of innate immunity and is particularly important in neonates, in whom adaptive immunity has not yet completely developed. MBL deficiency and MBL2 gene polymorphisms are associated with an opsonization defect and have been associated with neonatal sepsis. Aim The aim of our study was to assess serum MBL levels and genotype MBL2 genes to determine whether they can serve as markers for predicting neonatal sepsis in neonatal intensive care units. Patients and Methods A case-control study was conducted with 114 neonates classified into two groups: the septic group included 64 neonates (41 preterm and 23 full-term infants), and the non-septic control group included 50 neonates (29 preterm and 21 full-term infants). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to genotype MBL2 gene exon 1 (rs1800450) and (rs1800451) SNPs. Enzyme-linked immunosorbent assay (ELISA) was used to measure MBL serum concentrations. Results The polymorphic genotypes BB and AC at codons 54 and 57, respectively, showed higher frequencies than the wild-type genotype (AA) (14.1% versus 12.9% and 28.1% versus 19.4% respectively) in both groups, and this difference was greater in the septic group than in the non-septic group; however, the differences did not reach statistical significance. The B and C allele frequencies were also higher in the septic group than in the non-septic group, but the differences did not reach statistical significance (p ¼ 0.282 and 0.394, respectively). The serum levels of MBL were significantly lower in the septic group than in the non-septic group (p ¼ 0.028). Conclusion This study found no association between MBL levels or MBL2 exon 1 genotypes or alleles and neonatal sepsis risk. Further studies with larger sample sizes are needed to determine the role of the MBL2 gene as a risk factor and early predictor of neonatal sepsis.
PloS one, 2017
Studies on the influence of mannose-binding lectin (MBL) deficiency on infection susceptibility in preterm infants have yielded controversial results. We investigated the association of genotype-based MBL levels with outcome in very-low-birth weight infants (VLBWI). We genotyped 3 genetic variants of MBL2 (rs1800450, rs1800451, rs5030737) in 6878 VLBWI. MBL plasma levels were categorized as normal (wild type, A/A), low (heterozygotes, A/O) or undetectable (homozygotes, O/O). Primary outcome was the effect of genotype-based MBL2 levels on blood-culture proven and clinical sepsis during primary stay in hospital. We also evaluated burden of infection within 24 months after discharge. We found no association between MBL levels and sepsis risk in the whole cohort. Infants without measurable MBL levels born between 32 0/7 to 36 6/7 weeks of gestation, however, had a higher rate of Gram-negative sepsis than infants with normal or reduced MBL levels. In a follow-up investigation at 24 month...
Clinical Microbiology and Infection, 2007
Mannose-binding lectin (MBL) plays an important role in the innate immune response. Three alleles in the MBL gene, and one allele of the promoter, independently cause low serum MBL levels as compared with the wild-type. This study investigated the relationship between MBL genotype and the occurrence of nosocomial infection among neonates in a neonatal intensive care unit (NICU). Prospectively gathered information concerning nosocomial infection was available for 742 neonates from a recently performed surveillance study in an NICU. DNA was isolated from Guthriecards for a subgroup of 204 neonates who stayed in the NICU for ‡4 days. After a pre-PCR for the MBL gene in blood spots on Guthriecards, mutations were analysed by real-time PCR to detect six mutations in the MBL gene. An MBL genotype could be determined for 186 neonates. As compared to term neonates, genotypes encoding MBL-deficient haplotypes were significantly more prevalent among pre-term neonates. Fortyone of these neonates developed sepsis, with blood cultures yielding coagulase-negative staphylococci in 25 cases. Pneumonia occurred in 30 cases, with various causative organisms. No relationship was found between MBL genotype and the risk of nosocomial sepsis or pneumonia, even after correction for birth-weight, perhaps because of an insufficient correlation between genotype and the concentration of functional MBL. In addition, most bloodstream infections in the NICU were caused by coagulasenegative staphylococci, to which MBL binds poorly.
Mannose‐binding lectin gene polymorphism and its effect on short term outcomes in preterm infants
Jornal De Pediatria (versão Em Português), 2020
Objective: Mannose-binding lectin, which belongs to the collectin family, is an acute-phase reactant that activates the complement system. This study aimed to investigate the effect of MBL2 gene polymorphism on short-term outcomes in preterm infants. Method: Infants of <37 gestational weeks who were admitted to the neonatal intensive care unit during a two-year period were enrolled in this prospective study. The neonates were categorized into two groups according to their MBL2 genotypes. Normal MBL2 genotype was defined as MBL2 wild-type (AA genotype), whereas mutant MBL2 genotype was defined as MBL2 variant-type (AO/OO genotype). The relationship between MBL2 genotype and short-term morbidity and mortality was evaluated. Results: During the two-year study period, 116 preterm infants were enrolled in this study. In MBL2 variant-type, mannose-binding lectin levels were significantly lower and incidences of mannose-binding lectin deficiency (MBL level < 700 ng/mL) were higher (p < 0.001). In this group, the prevalence of respiratory distress syndrome and mortality was significantly higher (p < 0.001, p = 0.03 respectively). In the MBL2 wild-type group, the prevalence of necrotizing enterocolitis (NEC) was higher (p = 0.01). Logistic regression analyses revealed that MBL2 variant-type had a significant effect on respiratory distress syndrome development (odds ratio, 5.1; 95% confidence interval, 2.2-11.9; p < 0.001). Conclusions: MBL2 variant-type and mannose-binding lectin deficiency are important risk factors for respiratory distress syndrome development in preterm infants. Additionally, there is an association between MBL2 wild-type and NEC. Further studies on this subject are needed.
Human Immunology, 2009
Circulating mannan (or mannose)-binding lectin (MBL) is genetically determined. Low MBL concentrations are associated with certain point mutations in the human MBL2 gene. Here we report the full MBL2 genotypes of 1800 Polish neonates and relate individual genotypes to serum MBL and MBL-dependent activity of the lectin pathway of complement activation. The seven acknowledged common haplotypes were found, plus the uncommon LYPD haplotype, combining to form 33 genotypes in this population. As expected, a strong correlation existed between genotypes and serum MBL or lectin pathway activity, and the latter two entities correlated strongly with each other. However, serum MBL values varied up to greater than 90-fold within genotypes. Unexpectedly, higher lectin pathway activity was found in association with the P allele relative to the Q allele. These data from a large cohort of neonates, representing an ethnically homogenous population, suggest that the current knowledge of the genetics of MBL2 is inadequate to predict serum MBL concentration and MBL-dependent lectin pathway activity in individual subjects.