Abstract (limited to 800 words)：.The insulin-like growth factor-I (IGF-I) and its related binding proteins (IGFBPs) form the IGF-IGFBP axis which play a major role in cell metabolism as well as in several medical aspects, including cancer and bone health. It is known that the variability in circulating IGF-I depend on the IGFBPs and these levels are partly genetically determined. Nevertheless, the interplay of the IGF-IGFBP axis protein levels and their association with gene polymorphism as well as the variability between populations are poorly understood and complex. To increase the understanding of the IGF-IGFBP interplay we propose a genotype-phenotype association study with single nucleotide polymorphism (SNPs) as genotypic markers and protein serum levels as quantitative trait in a multi-strain mouse model (n=8). Consequently, we present an association study between IGF-I, IGFBP-1, IGFBP-3 and SNPs. Genotyping of SNPs (n~50) in candidate genes will be performed. Candidate SNPs will be chosen in the relevant genes with emphasis of the genes coding directly for the IGF-IGFBP axis (Chr10 and Chr11) and relevant mediator genes of the IGF-I pathway like the growth hormone (GH, Chr11) and IGF receptors (IGF-IR, Chr7 and IGF-IIR, Chr17). Univariate analysis will be used to examine if SNPs, protein interplay or strains are determinants of the quantitative phenotype. Accordingly, a multivariate factor analysis (Principal Component analysis) will reveal which examined factor explains the variation of measured proteins and their interplay most. We assume that results of this study shed light on the determinating factors of the IGF-IGFBP axis and that the underlying genetic polymorphism of the pathway may offer future diagnostic and therapeutic opportunities.