Genetic and environmental influences of surfactant protein D serum levels.
The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate immune system, but SP-D is also present on extrapulmonary epithelial surfaces and in serum, where it has been used as a biomarker for pulmonary disease states. In this study, we investigate the mechanisms defining the constitutional serum level of SP-D and determine the magnitude of the genetic contribution to serum SP-D in the adult population. Recent studies have demonstrated that serum SP-D concentrations in children are genetically determined and that a single nucleotide polymorphism (SNP) located in the NH(2)-terminal region (Met11Thr) of the mature protein is significantly associated with the serum SP-D levels. A classic twin study was performed on a twin population including 1,476 self-reported healthy adults. The serum SP-D levels increased with male sex, age, and smoking status. The intraclass correlation was significantly higher for monozygotic (MZ) twin pairs than for dizygotic (DZ) twin pairs. Serum SP-D variance was influenced by nonshared environmental effects and additive genetic effects. Multivariate analysis of MZ and DZ covariance matrixes showed significant genetic correlation among serum SP-D and metabolic variables. The Met11Thr variant explained a significant part of the heritability indicating that serum SP-D variance could be decomposed into non-shared environmental effects (e(2) = 0.19), additive genetic effects (h(2) = 0.42), and the effect of the Met11Thr variations (q(2) = 0.39).
Sørensen
Grith L
GL
Medical Biotechnology Center, Institute for Medical Biology, University of Southern Denmark, Winsloewparken 25.3, DK-5000 Odense, Denmark. glsorensen@health.sdu.dk
Hjelmborg
Jacob v B
Jv
Kyvik
Kirsten O
KO
Fenger
Mogens
M
Høj
Anette
A
Bendixen
Christian
C
Sørensen
Thorkild I A
TI
Holmskov
Uffe
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004777:Environment; D014644:Genetic Variation; D006801:Humans; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood* / Q000235:genetics*; D012042:Registries; D014427:Twins
D037663:Pulmonary Surfactant-Associated Protein D