Study of the effect of DNA polymorphisms in the mannose-binding lectin gene (MBL2) on disease severity in Slovak cystic fibrosis patients

Abstract

Abstract. Lung infections are the leading cause of morbidity and mortality in cystic fibrosis (CF). Mannose-binding lectin (MBL) is a key factor in innate immunity. We therefore investigated whether MBL2 gene variants are associated with pulmonary function or susceptibility to Pseudomonas aeruginosa and Burkholderia cepacia infection in Slovak patients affected with CF. DNA polymorphisms in exon 1 and the promoter region were typed by single base primer extension assay in 91 patients and 100 healthy controls. The concentrations of MBL protein were determined in 34 patients by a sandwich enzyme-linked immunosorbent assay, and spirometric and microbiological data were collected from medical records. In this study we found that MBL2 genotypes were associated neither with earlier acquisition of P. aeruginosa or B. cepacia nor with reduced pulmonary function among patients. Although MBL2 genotypes were associated with the MBL2 protein serum level, results were statistically significant only for polymorphisms in exon 1, with p = 0.0008. The role of the MBL2 gene in lung disease severity in CF patients represents a very complex phenomenon where both genetic and environmental factors play an important role in addition to that of the MBL2 gene. Understanding this complexity requires further studies based on a broader scale of genetic factors involving both a whole-genome approach and a larger patient cohort. Key words: Cystic fibrosis -Mannose-binding lectin-polymorphism -Modifier gene -Lung functionAbbreviations: CF, cystic fibrosis; FEV 1 , forced expiratory volume in 1 second; MBL, mannosebinding lectin.

A SNaPshot Assay for Determination of the Mannose-Binding Lectin Gene Variants and an Algorithm for Calculation of Haplogenotype Combinations

“…Here, the SNaPshot assay was introduced for simultaneous genotyping of the six functional polymorphisms within the MBL2 gene. Similar assays have recently been used but none of these was designed for genotyping all six single nucleotide polymorphisms (SNPs) [ 21 , 22 , 23 , 24 ]. Due to the proximity of the individual analyzed SNPs, we performed a singleplex PCR reaction, which subsequently served as a template for the single-base extension (SBE) reaction.…”

Gene modifiers of cystic fibrosis lung disease: A systematic review

“…Mannose-binding lectin (MBL) is part of the innate immune response, and MBL deficiency is associated with increased susceptibility to infection. 35 MBL has been extensively studied as a gene modifier, with a number of studies 21,24,25,32,[36][37][38][39][40][41][42][43][44][45][46][47] showing as hypothesized, a low MBL production genotype is associated with several measures of more severe lung disease, such as higher infection rates, lower lung function, and lower survival. Of note the most robust study found no effect of MBL.…”