Polymorphisms in the human surfactant protein-D (SFTPD) gene:: strong evidence that serum levels of surfactant protein-D (SP-D) are genetically influenced

The collectin surfactant protein-D (SP-D) plays a significant role in innate immunity. Epidemiological studies described associations between single nucleotide polymorphisms ( SNPs) of the human gene coding surfactant protein-D ( SFTPD) and infectious pulmonary diseases. Studies on twins indicated very strong genetic dependence for serum levels of SP- D. The aim of this study was to determine the genetic influence of sequence variations within the SFTPD gene on the constitutional serum SP- D levels. We sequenced the 5' untranslated region (5'UTR), the coding region and the 3' region of the SFTPD gene of 32 randomly selected blood donors. Six validated SNPs were genotyped with sequence-specific probes ( TaqMan 7000) in 290 German blood donors. Serum SP- D levels were analysed by ELISA, and the association of SFTPD haplotype estimates with the quantitative phenotype serum SP- D level was determined. One single SFTPD haplotype ( allele frequency 13.53%) revealed a negative association with serum SP- D levels ( P < 0.0001). This was confirmed in a second prospectively collected group of blood donors ( n= 160, P= 0.0034). The discovery of a frequent negative variant of the SFTPD gene provides a basis for genetic analysis of the function of SP-D in the resistance against pulmonary infections and inflammatory disorders in humans.