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1 Medical Biotechnology Center, University of Southern Denmark, Odense, Denmark
2 The Danish Twin Registry, University of Southern Denmark, Odense, Denmark
3 The Department of Clinical Biochemistry, Copenhagen University Hospital, Hvidovre, Denmark
4 The Department of Animal Breeding and Genetics, The Danish Institute of Agricultural Sciences, Tjele, Denmark
5 The Danish Epidemiology Science Centre, Copenhagen University Hospital, Copenhagen, Denmark
* To whom correspondence should be addressed. E-mail: glsorensen{at}health.sdu.dk.
The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate immune system, but SP-D is also present on extra-pulmonary 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 located in the N-terminal region (Met11Thr) of the mature protein is significantly associated to the serum SP-D levels. A classical twin study was performed on a twin population including 1476 self-reported healthy adults. The serum SP-D levels increased with male sex, age and smoking and were adjusted herefore. The intraclass correlation was significantly higher for monozygotic (MZ) twin pairs than for dizygotic (DZ) twin pairs. Serum SP-D variance was influenced by non-shared environmental effects and additive genetic effects. Multivariate analysis of MZ and DZ covariance matrices 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 the E component (e2 = 0.19), additive genetic effects (h2 = 0.42), and the effect of the Met11Thr variations (q2 = 0.39).
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