PNPLA3 p.I148M variant is associated with greater reduction of liver fat content after bariatric surgery
PNPLA3 p.I148M variant is associated with greater reduction of liver fat content after bariatric surgery
复制标题
DOI：
10.1016/j.soard.2016.06.004
复制
发表时间：
2016-12-01
影响因子：
3.1
通讯作者：
Banales, Jesus M.
中科院分区：
文献类型：
--
作者：
Krawczyk, Marcin;Jimenez-Agueero, Raul;Banales, Jesus M.
背景：肥胖是非酒精性脂肪性肝病（NAFLD）的主要诱因。NAFLD进一步受到含马铃薯糖蛋白样磷脂酶结构域3（PNPLA3）p.I148M、跨膜6超家族成员2（TM6SF2）p.E167K和含膜结合O-酰基转移酶结构域7（MBOAT7）rs641738变体的青睐。目的：研究PNPLA3、TM6SF2和MBOAT7基因型与减肥手术结果之间的关系。方法：我们监测了84名计划进行减肥手术的肥胖个体（体重指数35 - 64 kg/m2）。使用限制性片段长度多态性分析和TaqMan测定对PNPLA3 p.I148M、TM6SF2 p.E167K和MBOAT7 rs641738变体进行基因分型。在手术前通过分析肝活检样本和一种新的基于磁共振成像的方程来确定肝脂肪变性。结果：PNPLA3等位基因[M]的存在与肝脏甘油三酯含量增加（P = 0.03）、磁共振成像检测到的脂肪变性（P = 0.04）和血清葡萄糖浓度降低（P = 0.04）相关。TM6SF2和MBOAT7均未增加肝脂肪变性（均P> 0.05）;然而，MBOAT7多态性与甘油三酯、总胆固醇、低密度脂蛋白和血糖水平升高相关（均P <0.05）。与具有普通基因型的个体相比，携带前列腺脂肪变性PNPLA3等位基因[M]的患者在手术后一年减轻了更多的体重（P <0.01）和肝脏脂肪（P = 0.04）。PNPLA3基因型和脂肪变性的初始等级是NAFLD改善的独立预测因子，而不是TM6SF2或MBOAT7变体（分别为P = 0.03和P <0.01）。结论：在肥胖患者中，与PNPLA3野生型等位基因携带者相比，PNPLA3 p.I148M等位基因的存在可能与减肥手术后肝脂肪变性的更大改善相关。(C)2016年美国代谢和减肥外科学会。All rights reserved.
Background: Obesity is the major trigger of nonalcoholic fatty liver disease (NAFLD). NAFLD is further favored by the patatin-like phospholipase domain-containing 3 (PNPLA3) p.I148M, trans membrane 6 superfamily member 2 (TM6SF2) p.E167K, and membrane-bound O-acyltransferase domain containing 7 (MBOAT7) rs641738 variants.Objectives: To investigate the relationship between the PNPLA3, TM6SF2, and MBOAT7 genotypes and the outcomes of bariatric surgery.Setting: University hospital.Methods: Prospectively we monitored 84 obese individuals (body mass index 35-64 kg/m(2)) scheduled for bariatric surgery. The PNPLA3 p.I148M, TM6SF2 p.E167K, and MBOAT7 rs641738 variants were genotyped using restriction fragment length polymorphism analysis and TaqMan assays. Hepatic steatosis was determined before surgery using analysis of liver biopsy samples and a novel magnetic resonance imaging based equation. One year later, steatosis was reevaluated by magnetic resonance imaging.Results: The presence of the PNPLA3 allle [M] was associated with increased hepatic triglyceride content (P = .03), steatosis detected by magnetic resonance imaging (P = 0.04), and decreased serum glucose concentrations (P = .04). Neither variant TM6SF2 nor MBOAT7 increased hepatic steatosis (all P > .05); however, the MBOAT7 polymorphism was associated with increased triglyceride, total cholesterol, low density lipoprotein, and serum glucose levels (all P < .05). Patients carrying the prosteatotic PNPLA3 allele [M] lost more weight (P < .01) and liver fat (P = .04) one year after surgery, as compared to individuals having the common genotype. The PNPLA3 genotype and initial grade of steatosis, but not the TM6SF2 or MBOAT7 variants, were independent predictors of NAFLD improvement (P = .03 and P < .01, respectively).Conclusion: In obese patients, the presence of the PNPLA3 p.I148M allele might be associated with greater improvement of hepatic steatosis after bariatric surgery in comparison to carriers of PNPLA3 wild-type alleles. (C) 2016 American Society for Metabolic and Bariatric Surgery. All rights reserved.