SP-A1, -A2 and -D belong to the collectin subgroup of the C-type lectin superfamily, and contain both collagen-like and carbohydrate-binding recognition domains (CRDs) [4]. Upon binding to pathogen-associated molecular selleck chem patterns (PAMPs), SP-A and SP-D enhance the opsonophagocytosis of common respiratory pathogens by macrophages [5,6]. Mice rendered SP-A or SP-D deficient exhibit increased susceptibility to several bacteria and viruses after intratracheal challenge [7-9]. SP-A1, -A2 and -D also play a pivotal role in the regulation of inflammatory responses [4,10,11] and clearance of apoptotic cells [4,12,13]. In mice, SP-A and SP-D have been shown to be non-redundant in the immune defense in vivo [9].The human SP-A locus consists of two similar genes, SFTPA1 and SFTPA2, located on chromosome 10q21-24, within a cluster that includes the SP-D gene (SFTPD) [11].

The nucleotide sequences of human SFTPA1 and SFTPA2 differ little (96.0 to 99.6%) [14]. Single nucleotide polymorphisms (SNP) at the SFTPA1 codons 19, 50, 62, 133 and 219, and at the SFTPA2 codons 9, 91, 140 and 223 have been used to define the SP-A haplotypes, which are conventionally denoted as 6An for the SFTPA1 gene and 1An for the SFTPA2 gene (see Table E1 in Additional File 1) [15]. Variability at the SFTPD gene has been also reported. Particularly, the presence of the variant amino acid (aa)-11 (M11T) has been shown to lead to low SP-D levels [16].In the present study, we assessed the potential association of missense polymorphisms of the SFTPA1, SFTPA2 and SFTPD genes as well as the resulting haplotypes, with the susceptibility to and the severity and outcome of CAP in adults.

In addition, we evaluated the existence of linkage disequilibrium (LD) among these genes, and the effect of genetic variability on SP-D serum levels.Materials and methodsPatients and controlsWe studied 682 patients and 769 controls, all of them Caucasoid Spanish adult individuals from five hospitals in Spain. Foreigners and individuals with ancestors other than Spanish were previously excluded in the selection process. The diagnosis of CAP was assumed in the presence of acute onset of signs and symptoms suggesting lower respiratory tract infection and radiographic evidence of a new pulmonary infiltrate that had no other known cause. A detailed description of the exclusion criteria and clinical definitions are shown in Methods in Additional File 1[17-19].

The control group was composed of healthy unrelated blood donors from the same hospitals as patients.For susceptibility, a case-control study was performed. Severity and outcome were evaluated in Dacomitinib a prospective study of CAP patients. Demographic and clinical characteristics of CAP patients included in the study are shown in Table E2 in Additional File 1.