Association of FCN1 and FCN2 gene polymorphisms with earlier onset of chronic pseudomonas aeruginosa (Pa) colonisation in cystic fibrosis (CF) patients

Background: CF is a multisystem disease with high degree of phenotypic variability especially in lung disease.Modifying genes of innate immunity may be involved in early onset of Pa colonisation. Methods: 82 Single Nucleotide Polymorphisms (SNPs) in 22 genes contributing to the innate immunity (MBL2, MASP (MBL associated serine Protease) 1/2/3, FCN (Ficolin) 1/2, LBP (Lipopolysaccharide-binding Protein), CD14,TLR (Toll-likereceptors 1→10)) were genotyped in a cohort of 116 CF patients. (age 6-44 years) Association survival analysis (Kaplan Meier and Cox regression) using additive, recessive, dominant and codominant model was performed looking for an association between SNPs and age of onset of Pa colonisation in all CF patients. Results: CF patients being heterozygous or homozygous for the mutant allel of both linked SNPs FCN1 (promoter) (A/G) and FCN1 (Q272Q) (exon 9) (G>A) are earlier colonised with Pa (p=0,016,p=0,026 resp). Earlier onset of Pa colonisation is seen in CF patients homozygous for mutant allel of -64A>C polymorphism FCN2 (promoter) (p=0,0031) and in patients having at least one mutant allel of the linked S258A (G>T)) polymorphism FCN2 (p=0,0057). CF patients heterozygous for mutant allel of TLR10 (rs7694115) (promoter) (T>C) (p=0,026) and linked SNP (rs11096957) (ex3) (N241H) (p=0,0113) and SNPs (rs11466645) (pro) (T>A) (p=0,0068), (rs11096956) (ex3) (P344P) (p=0,0067) are significantly later colonised with Pa . Conclusion: Mutant allel of SNPs FCN1 (pro and Q272Q) and FCN2 (-64A>C and S258A) is significantly associated with earlier Pa colonisation. Mutant allel of polymorphism of TLR10 is associated with later onset of Pa colonisation.