Association of polymorphisms in GCKR and TRIB1 with nonalcoholic fatty liver disease and metabolic syndrome traits
スポンサーリンク
概要
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In several genome-wide association studies, nonalcoholic fatty liver disease and alanine aminotransferase susceptibility variants have been identified in several genes, including LYPLAL1, ZP4, GCKR, HSD17B13, PALLD, PPP1R3B, FDFT1, TRIB1, COL13A1, CPN1, ERLIN1, CWF19L1, EFCAB4B, PZP, and NCAN. 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 GCKR rs780094, TRIB1 rs2954021, and PNPLA3 rs738409 for epistatic effects. The A-allele of rs780094 in GCKR (P = 0.0024) and the A-allele of rs2954021 TRIB1 (P = 4.5×10-5) were significantly associated with nonalcoholic fatty liver disease. GCKR rs780094 was also associated with decreased plasma glucose, and increased triglycerides in the patient and control groups. GCKR rs780094 was also associated with an increased ratio of visceral to subcutaneous fat area in the patients with nonalcoholic fatty liver disease. Variations in GCKR, TRIB1, and PNPLA3 independently influenced nonalcoholic fatty liver disease and had no epistatic effects. Our data suggest variations in GCKR and TRIB1 are involved in the development of nonalcoholic fatty liver disease.
著者
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Ueno Takato
Research Center For Innovative Cancer Therapy And Second Department Of Internal Medicine Kurume Univ
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Ogawa Yuji
Division Of Cardiology Asahikawa Kosei Hospital
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Chayama Kazuaki
Deparmtment Of Gastroenterology Toranomon Hospital
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Hyogo Hideyuki
Department Of Medicine And Molecular Science Graduate School Of Biomedical Sciences Hiroshima Univer
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Yoneda Masato
Division Of Gastroenterology Yokohama City University
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Ochi Hidenori
Department Of Medicine And Molecular Science Division Of Frontier Medical Science Programs For Biomedical Research Graduate School Of Biomedical Sciences Hiroshima University
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Nakamura Takahiro
Laboratory For Mathematics National Defense Medical College
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NAKAJIMA Atsushi
Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University
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Nakao Kazuwa
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
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Ogawa Yuji
Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
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Kitamoto Aya
Medical Research Support Center, Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
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Kitamoto Takuya
Medical Research Support Center, Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
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Mizusawa Seiho
Medical Research Support Center, Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
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Sekine Akihiro
Medical Research Support Center, Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
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Hotta Kikuko
Medical Research Support Center, Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
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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
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