rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis.
rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis.
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DOI：
10.1016/j.jhep.2020.08.027
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发表时间：
2021-01
影响因子：
25.7
通讯作者：
Mann JP
中科院分区：
文献类型：
--
作者：
Teo K;Abeysekera KWM;Adams L;Aigner E;Anstee QM;Banales JM;Banerjee R;Basu P;Berg T;Bhatnagar P;Buch S;Canbay A;Caprio S;Chatterjee A;Ida Chen YD;Chowdhury A;Daly AK;Datz C;de Gracia Hahn D;DiStefano JK;Dong J;Duret A;EU-PNAFLD Investigators;Emdin C;Fairey M;Gerhard GS;GOLD Consortium;Guo X;Hampe J;Hickman M;Heintz L;Hudert C;Hunter H;Kelly M;Kozlitina J;Krawczyk M;Lammert F;Langenberg C;Lavine J;Li L;Lim HK;Loomba R;Luukkonen PK;Melton PE;Mori TA;Palmer ND;Parisinos CA;Pillai SG;Qayyum F;Reichert MC;Romeo S;Rotter JI;Im YR;Santoro N;Schafmayer C;Speliotes EK;Stender S;Stickel F;Still CD;Strnad P;Taylor KD;Tybjærg-Hansen A;Umano GR;Utukuri M;Valenti L;Wagenknecht LE;Wareham NJ;Watanabe RM;Wattacheril J;Yaghootkar H;Yki-Järvinen H;Young KA;Mann JP
MBOAT 7附近的一种常见遗传变异（rs641738 C>T）先前与NAFLD中的肝脂肪和晚期组织学相关;然而，这些发现在文献中并没有得到一致的重复。我们的目的是确定rs641738 C>T是否是NAFLD的一个危险因素，并通过荟萃分析证实其在相关代谢表型调节中的作用。我们对rs641738 C>T基因型与肝脏脂肪、NAFLD组织学和血清丙氨酸氨基转移酶（ALT）、脂质或胰岛素之间相关性的研究数据进行了荟萃分析。这些包括直接基因分型研究和全基因组关联研究（GWAS）的人群水平数据。我们使用隐性、加性和显性遗传模型进行了随机效应荟萃分析。来自42项研究的1，066，175名参与者（9，688名接受肝脏活检）的数据被纳入荟萃分析。在高加索成年人中，rs641738 C>T与CT/MRI显示的较高肝脏脂肪（+0.03标准差[95%CI 0.02-0.05]，pz = 4.8×10-5）和NAFLD的诊断（比值比[OR] 1.17 [95%CI 1.05-1.3]，pz = 0.003）相关。使用隐性遗传模型（CC + CT vs. TT），该变异体还与白人成人中晚期纤维化的存在呈正相关（OR 1.22 [95% CI 1.03-1.45]，pz = 0.021）。对既往GWAS数据的荟萃分析发现，该变体与ALT升高（pz = 0.002）和血清甘油三酯降低（pz = 1.5×10-4）相关。rs641738 C>T与空腹胰岛素无关，在NAFLD儿童中未观察到影响。我们的研究验证了MBOAT 7附近的rs641738 C>T作为欧洲血统个体中NAFLD存在和严重程度的风险因素。脂肪肝是一种常见的疾病，脂肪在肝脏中堆积，这会导致肝脏炎症和疤痕（包括“增生”）。它与肥胖和糖尿病密切相关，但一些基因也被认为是重要的。我们做这项研究是为了看看一个基因（“MBOAT 7”）中的一个特定变化（“变体”）是否与脂肪肝疾病有关。我们从40多项已发表的研究中获取数据，发现MBOAT 7附近的这种变异与更严重的脂肪肝疾病有关。这意味着设计用于MBOAT 7的药物可能有助于治疗脂肪肝。对42项研究（> 100万参与者）进行荟萃分析，以评估MBOAT 7附近的rs641738 C>T在NAFLD中的作用。rs641738 C>T与肝脂肪、ALT、肝纤维化和HCC呈正相关。rs641738 C>T与血清甘油三酯呈负相关。仅在高加索人群的研究中发现了一致的相关性。
A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in NAFLD; however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis. We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models. Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI 0.02–0.05], pz = 4.8×10–5) and diagnosis of NAFLD (odds ratio [OR] 1.17 [95% CI 1.05–1.3], pz = 0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI 1.03–1.45], pz = 0.021) in Caucasian adults using a recessive model of inheritance (CC + CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz = 0.002) and lower serum triglycerides (pz = 1.5×10–4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD. Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent. Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including ‘cirrhosis’). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change (‘variant’) in one gene (‘MBOAT7’) was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease. Meta-analysis of 42 studies (>1 million participants) to assess the role of rs641738C>T near MBOAT7 in NAFLD. rs641738C>T positively associated with liver fat, ALT, fibrosis and HCC. rs641738C>T negatively associated with serum triglycerides. Consistent associations found in studies of Caucasian populations only.
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影响因子：
5.1
作者：
Brouwers, Martijn C. G. J.;Simons, Nynke;Isaacs, Aaron
通讯作者：
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作者：
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通讯作者：
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通讯作者：
Valenti L