Association of polymorphisms in GCKR and TRIB1 with nonalcoholic fatty liver disease and metabolic syndrome traits
Association of polymorphisms in GCKR and TRIB1 with nonalcoholic fatty liver disease and metabolic syndrome traits
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DOI：
10.1507/endocrj.ej14-0052
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发表时间：
2014-07-01
影响因子：
2
通讯作者：
Hotta, Kikuko
中科院分区：
文献类型：
--
作者：
Kitamoto, Aya;Kitamoto, Takuya;Hotta, Kikuko
在几项全基因组关联研究中，已在多个基因中鉴定出非酒精性脂肪肝和丙氨酸转氨酶易感性变异，包括 LYPLAL1、ZP4、GCKR、HSD17B13、PALD、PPP1R3B、FDFT1、TRIB1、COL13A1、CPNI、ERLIN1、CWF19L1、EFCAB4B、PZP 和 NCAN。为了研究这些基因与日本人群非酒精性脂肪肝之间的关系，我们对 540 名患者和 1012 名对照受试者进行了 18 种变异的基因分型。我们进行了逻辑回归分析来表征测试的变异与非酒精性脂肪肝之间的关联。还通过线性回归分析代谢综合征和组织学特征。我们还检查了 GCKR rs780094、TRIB1 rs2954021 和 PNPLA3 rs738409 的上位效应。 GCKR中rs780094的A等位基因(P = 0.0024)和rs2954021 TRIB1的A等位基因(P = 4.5x10(-5))与非酒精性脂肪肝显着相关。 GCKR rs780094 还与患者和对照组的血浆葡萄糖降低和甘油三酯升高相关。 GCKR rs780094 还与非酒精性脂肪肝患者内脏脂肪面积与皮下脂肪面积之比增加相关。 GCKR、TRIB1 和 PNPLA3 的变异独立影响非酒精性脂肪肝，并且没有上位效应。我们的数据表明 GCKR 和 TRIB1 的变异与非酒精性脂肪肝疾病的发生有关。
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, CPNI, 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 = 4.5x10(-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.