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.
Heidinger
Kathrin
K
Institute of Clinical Immunology and Transfusion Medicine, University of Giessen, Langhansstrasse 7, 35392, Giessen, Germany. Kathrin.S.Heidinger@immunologie.med.uni-giessen.de
König
Inke R
IR
Bohnert
Anette
A
Kleinsteiber
Anja
A
Hilgendorff
Anne
A
Gortner
Ludwig
L
Ziegler
Andreas
A
Chakraborty
Trinad
T
Bein
Gregor
G
D000328:Adult; D000368:Aged; D001483:Base Sequence; D005260:Female; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood* / Q000235:genetics*
D037663:Pulmonary Surfactant-Associated Protein D