Genetic and environmental influences of surfactant protein D serum levels
Genetic and environmental influences of surfactant protein D serum levels
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DOI：
10.1152/ajplung.00487.2005
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发表时间：
2006-05-01
影响因子：
4.9
通讯作者：
Holmskov, U
中科院分区：
文献类型：
--
作者：
Sorensen, GL;Hjelmborg, JV;Holmskov, U
集合素表面活性蛋白D(SP-D)是肺天然免疫系统的重要组成部分，但也存在于肺外上皮细胞表面和血清中，被用作肺部疾病状态的生物标志物。在这项研究中，我们研究了决定SP-D的组成血清水平的机制，并确定了成年人群中SP-D的遗传贡献的大小。最近的研究表明，儿童的血清SP-D水平是由基因决定的，位于成熟蛋白NH2末端区域(Met11Thr)的单核苷酸多态性(SNP)与血清SP-D水平显著相关。一项经典的双胞胎研究在双胞胎人群中进行，其中包括1476名自我报告的健康成年人。血清SP-D水平随男性、年龄、吸烟状况的增加而升高。同卵双生子(MZ)的组内相关性显著高于同卵双生子(DZ)双生子。血清SP-D变化受非共有环境效应和加性遗传效应的影响。MZ和DZ协方差矩阵的多变量分析显示，血清SP-D和代谢变量之间存在显著的遗传相关性。Met11Thr变异解释了很大一部分遗传力，表明血清SP-D变异可以分解为非共享环境效应(e(2)=0.19)、加性遗传效应(h(2)=0.42)和Met11Thr变异的效应(q(2)=0.39)。
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 (e(2) = 0.19), additive genetic effects (h(2) = 0.42), and the effect of the Met11Thr variations (q(2) = 0.39).