Glucokinase regulatory protein gene polymorphism affects liver fibrosis in non-alcoholic fatty liver disease.
Glucokinase regulatory protein gene polymorphism affects liver fibrosis in non-alcoholic fatty liver disease.
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DOI：
10.1371/journal.pone.0087523
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Craxì A
中科院分区：
文献类型：
--
作者：
Petta S;Miele L;Bugianesi E;Cammà C;Rosso C;Boccia S;Cabibi D;Di Marco V;Grimaudo S;Grieco A;Pipitone RM;Marchesini G;Craxì A
与脂质和葡萄糖性状相关的葡萄糖激酶调节蛋白（GCKR）变异被认为影响脂肪肝浸润。我们的目的是评估GCKR rs780094 C→T SNP在校正PNPLA3基因型后是否影响NAFLD患者脂肪变性、小叶炎症和纤维化的表达。在366例连续NAFLD患者中（197例来自西西里岛，169例来自意大利中部/北部），我们评估了人体测量学、生化和代谢特征；肝活检按Kleiner评分。PNPLA3 rs738409 C b> G和GCKR rs780094 C>T单核苷酸多态性也进行了评估。在整个NAFLD队列的多因素logistic回归分析中，显著肝纤维化（>F1）的存在与高HOMA （OR 1.12, 95% CI 1.01-1.23, p = 0.02）、NAFLD活动评分≥5 （OR 4.09, 95% CI 2.45-6.81, p<0.001）和GCKR C>T SNP （OR 2.06, 95% CI 1.43-2.98, p<0.001）独立相关。单独考虑两个不同的NAFLD队列，观察到相似的结果。在整个队列中，GCKR C>T SNP也与较高的血清甘油三酯相关（方差分析，p = 0.02）。在NAFLD患者中，GCKR rs780094 C b> T与肝纤维化的严重程度和较高的血清甘油三酯水平相关。
Variant in glucokinase regulatory protein (GCKR), associated with lipid and glucose traits, has been suggested to affect fatty liver infiltration. We aimed to assess whether GCKR rs780094 C→T SNP influences the expression of steatosis, lobular inflammation and fibrosis in NAFLD patients, after correction for PNPLA3 genotype. In 366 consecutive NAFLD patients (197 from Sicily, and 169 from center/northern Italy), we assessed anthropometric, biochemical and metabolic features; liver biopsy was scored according to Kleiner. PNPLA3 rs738409 C>G and GCKR rs780094 C>T single nucleotide polymorphisms were also assessed. At multivariate logistic regression analysis in the entire NAFLD cohort, the presence of significant liver fibrosis (>F1) was independently linked to high HOMA (OR 1.12, 95% CI 1.01–1.23, p = 0.02), NAFLD activity score ≥5 (OR 4.09, 95% CI 2.45–6.81, p<0.001), and GCKR C>T SNP (OR 2.06, 95% CI 1.43–2.98, p<0.001). Similar results were observed considering separately the two different NAFLD cohorts. GCKR C>T SNP was also associated with higher serum triglycerides (ANOVA, p = 0.02) in the entire cohort. In patients with NAFLD, GCKR rs780094 C>T is associated with the severity of liver fibrosis and with higher serum triglyceride levels.
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影响因子：
13.5
作者：
Speliotes, Elizabeth K.;Butler, Johannah L.;Palmer, Cameron D.;Voight, Benjamin F.;Hirschhorn, Joel N.
通讯作者：
Hirschhorn, Joel N.
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作者：
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Pirola, Carlos J.