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Analysis of variants in three genes encoding oxysterol-binding protein (OSBP) homologues (OSBPL2, OSBPL9, OSBPL10) in Finnish families with familial low high-density lipoprotein (HDL) levels (N = 426) or familial combined hyperlipidemia (N = 684) revealed suggestive linkage of OSBPL10 single-nucleotide polymorphisms (SNPs) with extreme end high triglyceride (TG; >90th percentile) trait. Prompted by this initial finding, we carried out association analysis in a metabolic syndrome subcohort (Genmets) of Health2000 examination survey (N = 2,138), revealing association of multiple OSBPL10 SNPs with high serum TG levels (>95th percentile). To investigate whether OSBPL10 could be the gene underlying the observed linkage and association, we carried out functional experiments in the human hepatoma cell line Huh7. Silencing of OSBPL10 increased the incorporation of [(3)H]acetate into cholesterol and both [(3)H]acetate and [(3)H]oleate into triglycerides and enhanced the accumulation of secreted apolipoprotein B100 in growth medium, suggesting that the encoded protein ORP10 suppresses hepatic lipogenesis and very-low-density lipoprotein production. ORP10 was shown to associate dynamically with microtubules, consistent with its involvement in intracellular transport or organelle positioning. The data introduces OSBPL10 as a gene whose variation may contribute to high triglyceride levels in dyslipidemic Finnish subjects and provides evidence for ORP10 as a regulator of cellular lipid metabolism.

The expression of insulin-like growth factor II (IGF-II) was analysed immunohistochemically in a series of 211 breast cancers with special reference to standard prognostic factors and patient survival. IGF-II was expressed both in the cancer cells and in stromal cells, in 84% and 50% of cases, respectively. IGF-II expression in cancer cells was related to a non-metastatic disease at diagnosis (p = 0.03), low tumour grade (p = 0.02), DNA diploidy (p = 0.02) and S-phase fraction under 7% (p = 0.001). IGF-II negativity was positively correlated to morphometric SD of nuclear area (p = 0.0003), nuclear perimetry (p = 0.002), SD of nuclear perimetry (p = 0.02), minimum nuclear diameter (p = 0.005) and maximum nuclear diameter (p = 0.003). The expression of IGF-II in stromal cells was related to low histological grade (p = 0.02), mitotic index under 10/mm2 (p = 0.01), mild nuclear pleomorphism (p = 0.03), DNA diploidy (p = 0.08), SD of nuclear area (p = 0.006), mean nuclear perimeter (p = 0.05), minimum nuclear diameter (p = 0.005) and maximum nuclear diameter (p = 0.007) in that the nuclear factor values were higher in tumours without stromal IGF-II expression. In univariate and multivariate survival analysis, immunohisto-chemically detected expression of IGF-II had no independent prognostic value over standard prognostic factors. Despite the fact that expression of IGF-II was inversely related to several histopathological features of malignancy, the clinical behaviour of breast cancer seemed to be independent of IGF-II expression.