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Genetic and environmental influences of surfactant protein D serum levels

¹Medical Biotechnology Center, Institute for Medical Biology, and ²The Danish Twin Registry, Epidemiology, Institute of Public Health, University of Southern Denmark, Odense; ³Department of Clinical Biochemistry, University Hospital of Copenhagen, Hvidovre; ⁴Department of Animal Breeding and Genetics, Danish Institute of Agricultural Sciences, Tjele; and ⁵Danish Epidemiology Science Centre, Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark

Submitted 17 November 2005 ; accepted in final form 15 December 2005

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 NH₂-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 (e² = 0.19), additive genetic effects (h² = 0.42), and the effect of the Met11Thr variations (q² = 0.39).

surfactant protein D polymorphism; serum marker; interaction of gene and environment; innate immunity

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