Association of polymorphisms in <i>GCKR</i> and <i>TRIB1</i> with nonalcoholic fatty liver disease and metabolic syndrome traits

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Author(s)

    • Kitamoto Aya
    • Medical Research Support Center, Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
    • Nakao Kazuwa
    • Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
    • Sekine Akihiro
    • Medical Research Support Center, Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
    • Chayama Kazuaki
    • Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
    • Nakajima Atsushi
    • Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
    • Hotta Kikuko
    • Medical Research Support Center, Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
    • Kitamoto Takuya
    • Medical Research Support Center, Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
    • Nakamura Takahiro
    • Laboratory for Mathematics, National Defense Medical College, Tokorozawa 359-8513, Japan
    • Ogawa Yuji
    • Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
    • Yoneda Masato
    • Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
    • Hyogo Hideyuki
    • Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
    • Ochi Hidenori
    • Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
    • Mizusawa Seiho
    • Medical Research Support Center, Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
    • Ueno Takato
    • Research Center for Innovative Cancer Therapy, Kurume University, Kurume 830-0011, Japan

Abstract

In several genome-wide association studies, nonalcoholic fatty liver disease and alanine aminotransferase susceptibility variants have been identified in several genes, including <i>LYPLAL1</i>, <i>ZP4</i>, <i>GCKR</i>, <i>HSD17B13</i>, <i>PALLD</i>, <i>PPP1R3B</i>, <i>FDFT1</i>, <i>TRIB1</i>, <i>COL13A1</i>, <i>CPN1</i>, <i>ERLIN1</i>, <i>CWF19L1</i>, <i>EFCAB4B</i>, <i>PZP</i>, and <i>NCAN</i>. To investigate the relationship between these genes and nonalcoholic fatty liver disease in the Japanese population, we genotyped 540 patients and 1012 control subjects for 18 variations. We performed logistic regression analyses to characterize the association between the tested variations and nonalcoholic fatty liver disease. Metabolic syndrome and histological traits were also analyzed by linear regression. We also examined <i>GCKR</i> rs780094, <i>TRIB1</i> rs2954021, and <i>PNPLA3</i> rs738409 for epistatic effects. The A-allele of rs780094 in <i>GCKR</i> (<i>P</i> = 0.0024) and the A-allele of rs2954021 <i>TRIB1</i> (<i>P</i> = 4.5×10<sup>-5</sup>) were significantly associated with nonalcoholic fatty liver disease. <i>GCKR</i> rs780094 was also associated with decreased plasma glucose, and increased triglycerides in the patient and control groups. <i>GCKR</i> rs780094 was also associated with an increased ratio of visceral to subcutaneous fat area in the patients with nonalcoholic fatty liver disease. Variations in <i>GCKR</i>, <i>TRIB1</i>, and <i>PNPLA3</i> independently influenced nonalcoholic fatty liver disease and had no epistatic effects. Our data suggest variations in <i>GCKR</i> and <i>TRIB1</i> are involved in the development of nonalcoholic fatty liver disease.

Journal

  • Endocrine Journal

    Endocrine Journal 61(7), 683-689, 2014

    The Japan Endocrine Society

Codes

  • NII Article ID (NAID)
    130004677938
  • NII NACSIS-CAT ID (NCID)
    AA10901436
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    0918-8959
  • Data Source
    IR  J-STAGE 
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