Genetic variability at the surfactant proteins A and D in susceptibility and severity of pneumonia

Introduction

Genetic variability of the pulmonary surfactant proteins A and D may affect clearance of microorganisms and the extent of the inflammatory response. The genes of these collectins (SFTPA1, SFTPA2 and SFTPD) are located in a cluster at 10q21-24, near to the gene coding for mannose-binding lectin (MBL2), another collectin involved in innate immunity. The aim of this study was to evaluate the association of variability at SFTPA1, SFTPA2 and SFTPD with susceptibility to and severity of community-acquired pneumonia (CAP). Another objective was to evaluate the existence of linkage disequilibrium among SFTPA1, SFTPA2, SFTPD and MBL2.

Methods

Nonsynonymous polymorphisms of SFTPA1, SFTPA2, SFTPD and MBL2 were analysed in 682 CAP patients and 769 controls. Haplotypes were inferred and linkage disequilibrium (LD) was characterized. The effect of genetic variability on SP-A and SP-D serum levels was studied.

Results

Haplotypes SFTPA1 6A2 (P = 0.0009), SFTPA2 1A0 (P = 0.0017), and SFTPA1-SFTPA2 6A2-1A0 (P = 0.0005) were under-represented in patients, whereas haplotypes SFTPA2 1A10 (P = 0.00007) and SFTPA1-SFTPA2 6A3-1A (P = 0.00065) were over-represented. We observed the existence of LD among the studied genes. Chromosomes carrying the SFTP-D aa11-C allele with 6A2-1A0 and the XA variant of MBL2 were found to be even more under-represented in patients (P = 0.00008). 1A10 and 6A-1A were associated with higher mortality, and also with multiorgan dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS), respectively. SFTPD aa11-C allele was associated with development of MODS and ARDS.

Conclusions

We report for the first time an association between genetic variants of SFTPA1, SFTPA2 and SFTPD with the susceptibility, severity and outcome of pneumonia.