OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism

Julia Perttilä, Krista Merikanto, Jussi Naukkarinen, Ida Liisa Surakka, Nicolas W. Martin, Kimmo Tanhuanpää, Vinciane Grimard, Marja-Riitta Taskinen, Christoph Thiele, Veikko Salomaa, Antti Jula, Markus Perola, Ismo Virtanen, Leena Palotie, Vesa M. Olkkonen

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    "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 [H-3]acetate into cholesterol and both [H-3]acetate and [H-3]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."
    Original languageEnglish
    JournalJournal of Molecular Medicine
    Volume87
    Issue number8
    Pages (from-to)825-835
    Number of pages11
    ISSN0946-2716
    DOIs
    Publication statusPublished - 2009
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine
    • 312 Clinical medicine
    • 318 Medical biotechnology
    • 217 Medical engineering
    • 118 Biological sciences

    Cite this

    Perttilä, Julia ; Merikanto, Krista ; Naukkarinen, Jussi ; Surakka, Ida Liisa ; Martin, Nicolas W. ; Tanhuanpää, Kimmo ; Grimard, Vinciane ; Taskinen, Marja-Riitta ; Thiele, Christoph ; Salomaa, Veikko ; Jula, Antti ; Perola, Markus ; Virtanen, Ismo ; Palotie, Leena ; Olkkonen, Vesa M. / OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism. In: Journal of Molecular Medicine. 2009 ; Vol. 87, No. 8. pp. 825-835.
    @article{4afc130e31984678bbba113e8c70b86a,
    title = "OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism",
    abstract = "{"}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 [H-3]acetate into cholesterol and both [H-3]acetate and [H-3]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.{"}",
    keywords = "311 Basic medicine, 312 Clinical medicine, 318 Medical biotechnology, 217 Medical engineering, 118 Biological sciences",
    author = "Julia Perttil{\"a} and Krista Merikanto and Jussi Naukkarinen and Surakka, {Ida Liisa} and Martin, {Nicolas W.} and Kimmo Tanhuanp{\"a}{\"a} and Vinciane Grimard and Marja-Riitta Taskinen and Christoph Thiele and Veikko Salomaa and Antti Jula and Markus Perola and Ismo Virtanen and Leena Palotie and Olkkonen, {Vesa M.}",
    year = "2009",
    doi = "10.1007/s00109-009-0490-z",
    language = "English",
    volume = "87",
    pages = "825--835",
    journal = "Journal of Molecular Medicine",
    issn = "0946-2716",
    publisher = "Springer Heidelberg",
    number = "8",

    }

    Perttilä, J, Merikanto, K, Naukkarinen, J, Surakka, IL, Martin, NW, Tanhuanpää, K, Grimard, V, Taskinen, M-R, Thiele, C, Salomaa, V, Jula, A, Perola, M, Virtanen, I, Palotie, L & Olkkonen, VM 2009, 'OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism' Journal of Molecular Medicine, vol. 87, no. 8, pp. 825-835. https://doi.org/10.1007/s00109-009-0490-z

    OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism. / Perttilä, Julia; Merikanto, Krista; Naukkarinen, Jussi; Surakka, Ida Liisa; Martin, Nicolas W.; Tanhuanpää, Kimmo; Grimard, Vinciane; Taskinen, Marja-Riitta; Thiele, Christoph; Salomaa, Veikko; Jula, Antti; Perola, Markus; Virtanen, Ismo; Palotie, Leena; Olkkonen, Vesa M.

    In: Journal of Molecular Medicine, Vol. 87, No. 8, 2009, p. 825-835.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism

    AU - Perttilä, Julia

    AU - Merikanto, Krista

    AU - Naukkarinen, Jussi

    AU - Surakka, Ida Liisa

    AU - Martin, Nicolas W.

    AU - Tanhuanpää, Kimmo

    AU - Grimard, Vinciane

    AU - Taskinen, Marja-Riitta

    AU - Thiele, Christoph

    AU - Salomaa, Veikko

    AU - Jula, Antti

    AU - Perola, Markus

    AU - Virtanen, Ismo

    AU - Palotie, Leena

    AU - Olkkonen, Vesa M.

    PY - 2009

    Y1 - 2009

    N2 - "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 [H-3]acetate into cholesterol and both [H-3]acetate and [H-3]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."

    AB - "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 [H-3]acetate into cholesterol and both [H-3]acetate and [H-3]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."

    KW - 311 Basic medicine

    KW - 312 Clinical medicine

    KW - 318 Medical biotechnology

    KW - 217 Medical engineering

    KW - 118 Biological sciences

    U2 - 10.1007/s00109-009-0490-z

    DO - 10.1007/s00109-009-0490-z

    M3 - Article

    VL - 87

    SP - 825

    EP - 835

    JO - Journal of Molecular Medicine

    JF - Journal of Molecular Medicine

    SN - 0946-2716

    IS - 8

    ER -