Function
The hydrophilic surfactant proteins SP-A and SP-D are members of the C-type lectin family of innate defense molecules. They are involved in host defense against microorganisms and inflammatory processes in the lung ¹⁾. SP-A enhances phagocytosis by alveolar macrophages and the production of cytokines by other defense cells ²⁾. SP-A is further involved in lung surfactant structure and regulation of surfactant synthesis and recycling ^1,3).

SP-D is involved in anti-inflammatory processes and mediates phagocytosis and agglutination of pathogens.

SFTPA
SP-A is encoded by two 94% identical genes SFTPA1 and SFTPA2 on chromosome 10q22-q23 ^4,5). A regulated expression enables two SP-A1 proteins of 248 amino acids to associate with one SP-A2 protein of 248 amino acids to trimeric structures, which then associates to the more complex 18-meric active SP-A structure homologous to the Mannose Binding Lectin (MBL) ⁶⁾.

The SFTPA genes both contain 4 coding exons and 3 non-coding 5’-exons that splice in different ways to give a number of variant 5’ UTR-transcripts ²⁸⁾. For the SFTPA1 gene, 5 main allelic variants (6A, 6A²-6A⁵) are known, for the SFTPA2 gene, 6 main allelic variants are known (1A, 1A⁰-1A⁴)¹⁾. Differences among allelic variants have been observed in the ability to enhance cytokine production or phagocytosis by alveolar macrophages and in the ability to aggregate lipopolysacharides (LPS) ²⁾.

SFTPD
The SFTPD gene is localized closely to SFTPA on chromosome 10q23.3 It contains 8 exons, of which 7 are encoding the 355 amino acid SP-D protein ^1,7,8). SP-D monomers combine to the active 12-meric "cross" structure, homologous to conglutinin.

SP-A and SP-D in lung disease
In contrast to the surfactant related genes SFTPB, SFTPC and ABCA3, no lethal mutations in the genes for SP-A and SP-D have been reported. SP-A and SP-D "knock-out mice" survive, but are impaired in clearing microorganisms from the lung and show a deregulation of surfactant phospholipid homeostasis underlining the role of both genes in host defense and surfactant regulation ^{9, 10, 11,12)}.
The protein levels of SP-A and SP-D are altered in various lung diseases such as pulmonary alveolar proteinosis (PAP), acute respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), interstitial pneumonia with collagen vascular disease (IPCD), asthma, sarcoidosis and chronic obstructive pulmonary disease (COPD) ^1,13).

Certain SP-A genotypes have been associated with the level of SP-A expression, and with the outcome and the risk of developing RDS at premature birth ^{14, 15)}. The SFTPA1 allele 6A² and the haplotype 6A²/1A⁰ in interaction with the SFTPB polymorphism Thr¹³¹ were associated with genetic susceptibility to premature RDS whereas the SFTPA alleles 1A⁰ and 6A³ were protective factors against RDS ^{15, 16)}.

The SPA1 allele 6A⁴ (Arg²¹⁹Trp) was associated with idiopathic pulmonary fibrosis in non-smokers ¹⁷⁾. SPA1 polymorphisms have been associated with tuberculosis in the Ethiopian and Mexican populations ^{18, 19)}.

Two heterozygous mutations in SFTPA2 (Gly²³¹Val and Phe¹⁹⁸Ser) have been found associated with Idiopathic Pulmonary Fibrosis ²⁰⁾. Polymorphisms in the SFTPA genes also have been linked to RSV bronchiolitis, otitis media and the risk of developing asthma in infants ^21,22,23).

SFTPD polymorphisms gene have been associated with serum protein levels of SP-D and infectious pulmonary diseases ²⁴⁾ as well as with postnatal pulmonary adaptation in preterm infants ²⁵⁾ and COPD ^26,27).

SPA gene analysis
The polymorphisms in both SP-A genes can be analyzed. To do this, we amplify the SP-A1 and SP-A2 genes separately and, by nested amplification, we isolate and sequence the protein-coding exons and their flanking intron sequences.

SP-D gene analysis
The 7 protein-coding exons are amplified from the genomic DNA of a patient, and screened for mutations and polymorphisms by DNA sequencing.

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