Association of polymorphisms in GCKR and TRIB1 with nonalcoholic fatty liver disease and metabolic syndrome traits

Endocrine Journal

Takato Ueno⁶  Aya Kitamoto³  Kazuaki Chayama⁴  Atsushi Nakajima²  Masato Yoneda²  Kikuko Hotta³  Hidenori Ochi⁴  Takuya Kitamoto³  Yuji Ogawa²  Takahiro Nakamura⁵  Seiho Mizusawa³  Hideyuki Hyogo⁴  Akihiro Sekine³  Kazuwa Nakao¹ 

[1] Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan;Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan;Medical Research Support Center, Pharmacogenomics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan;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;Laboratory for Mathematics, National Defense Medical College, Tokorozawa 359-8513, Japan;Research Center for Innovative Cancer Therapy, Kurume University, Kurume 830-0011, Japan

关键词: GCKR;    TRIB1;    Nonalcoholic fatty liver disease;    Metabolic syndrome;    Japanese;   

DOI  :  10.1507/endocrj.EJ14-0052

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(32)Cited-By(7)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.

【 授权许可】

Unknown