Editorial: opposite effects of genetic polymorphisms known to induce NAFLD on hepatic and cardiovascular outcomes in Chinese population
Editorial: opposite effects of genetic polymorphisms known to induce NAFLD on hepatic and cardiovascular outcomes in Chinese population
复制标题
社论：已知诱发 NAFLD 的基因多态性对中国人群肝脏和心血管结局的相反影响
DOI：
10.1111/apt.16818
复制
发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Fan JG
中科院分区：
文献类型：
--
作者：
Zhang RN;Fan JG
非酒精性脂肪性肝病(NAFLD)是一种与代谢功能障碍相关的脂肪肝病，存在于遗传易感人群中；它可进展到肝病的终末期，并增加心血管疾病(CVD)事件的风险。NAFLD的寿命显著缩短，心血管疾病、恶性肿瘤和肝病的死亡率增加。1.NAFLD的肝脏和肝外预后受多种因素的影响，包括基因多态性。13含棒状磷脂酶结构域的蛋白3(PNPLA3)、跨膜6超家族2(TM6SF2)和膜结合的糖基化转移酶结构域含蛋白7(MBOAT7)的基因变异参与了NAFLD的发生和发展。然而，这些遗传变异对心血管疾病事件的影响是复杂的，仍然存在争议。13 PNPLA3基因变异可能与心血管疾病风险没有因果关系，TM6SF2似乎是保护性的，MBOAT7可能对高加索人、西班牙裔和非裔美国人的心血管疾病风险起到中性作用。2，3 PNPLA3和TM6SF2都与较低的血浆三酰甘油和低密度脂蛋白(LDL)水平有关，并参与极低密度脂蛋白(VLDL)的产生，这可能解释了它们与心血管疾病的负面关系。3因此，与基因相关的NAFLD和与代谢相关的NAFLD可能对心血管疾病的发生产生不同的影响夏等5报道了上海长风社区5581名成人NAFLD相关基因变异与全因和特定死因死亡率的关系。在29425人的随访中，PNPLA3rs738409C>；G变异和PNPLA3、TM6SF2和MBOAT7风险等位基因的综合遗传易感性评分对超重/肥胖成年人的肝脏和心血管疾病死亡率显示出相反的影响。此外，超重/肥胖的NAFLD风险基因变异携带者1H核磁共振检测的血浆VLDL1和LDL2浓度显著降低。然而，与肥胖的NAFLD患者相比，瘦的NAFLD患者可能表现出相似的病因和CVD相关死亡率。据报道，PNPLA3 rs738409对瘦肉型个体的肝脏脂肪的影响大于超重/肥胖者；在亚洲人群中，PNPLA3 rs738409 GG基因型的百分比也高于亚洲人群中瘦肉型NAFLD。7在中心性肥胖患者中，瘦肉型NAFLD患颈动脉斑块的相对风险高于超重/肥胖相关的NAFLD。8中心型肥胖者在冠心病患者中死亡风险最高。9此外，性别和性激素与NAFLD和CVD有关，这两种疾病在男性和绝经后女性中更常见。10 PNPLA3 rs738409>；G对冠心病患者的影响
Nonalcoholic fatty liver disease (NAFLD) is a metabolic dysfunctionassociated fatty liver disease in genetically susceptible individuals; it can progress to endstage of liver disease and raise the risk of cardiovascular disease (CVD) events. NAFLD has significantly shortened lifespans with increased mortality from CVD, malignancies and liver diseases.1,2 The hepatic and extrahepatic outcomes of NAFLD are influenced by many factors including gene polymorphisms.13 Genetic variants of patatinlike phospholipase domaincontaining protein 3 (PNPLA3), transmembrane 6 superfamily 2 (TM6SF2) and membranebound Oacyltransferase domaincontaining protein 7 (MBOAT7) contribute to the pathogenesis and development of NAFLD. However, the effect of these genetic variants on CVD events are complicated and still in debate.13 The PNPLA3 genetic variant may not be causally associated with CVD risk, TM6SF2 appears to be protective and MBOAT7 may exert a neutral effect on CVD risk in Caucasian, Hispanic and African American ethnicities.2,3 Both PNPLA3 and TM6SF2 are associated with lower plasma levels of triacylglycerols and lowdensity lipoprotein (LDL), and also involved in very lowdensity lipoprotein (VLDL) production, which might explain their negative relationship with CVD.3 Therefore, ‘geneticrelated NAFLD’ and ‘metabolicrelated NAFLD’ might exert differential effects on cardiovascular outcomes.4 Recently, Xia et al.5 reported the associations of NAFLDrelated gene variants with allcause and causespecific mortality among 5581 adults from Changfeng community in Shanghai. During 29 425 personyears of followup, the PNPLA3 rs738409 C > G variant and a composite geneticpredisposition score of PNPLA3, TM6SF2 and MBOAT7 risk alleles presented the opposite effects on hepatic and cardiovascular mortality in adults with overweight/obesity. Moreover, plasma VLDL1 and LDL2 concentrations by 1Hnuclear magnetic resonance were significantly reduced in the NAFLD risk gene variant carriers with overweight/obesity. However, lean NAFLD patients might exhibit similar allcause and CVDrelated mortality compared to obese NAFLD individuals.6 Lin et al. reported that PNPLA3 rs738409 had a greater effect on liver fat in lean individuals than that in overweight/obese ones; the percentage of PNPLA3 rs738409 GG genotype was also higher in lean NAFLD in Asia population.7 In patients with central obesity, lean NAFLD had higher relative risk to carotid plaques than overweight/obesityrelated NAFLD.8 Lean individuals with central obesity was associated with the highest risk of mortality in patients with coronary artery disease.9 Furthermore, gender and sex hormones are associated with NAFLD and CVD, both diseases are more common in men and postmenopausal women.10 The effects of PNPLA3 rs738409 C > G on
登录
查看更多内容
亚洲人群中 NAFLD 相关基因多态性以及全因和特定原因死亡率：上海长风研究
影响因子：
7.6
作者：
Mingfeng Xia;Shuai Ma;Qingxia Huang;Hailuan Zeng;Jieyu Ge;Wenjie Xu;Qi Wu;Li Wu;Xiaoming Li;Hui Ma;Lingyan Chen;Qian Li;Qiqige Aleteng;Yu Hu;Wanyuan He;Baishen Pan;Hu;ong Lin;Yan Zheng;Sijia Wang;Huiru Tang;Xin Gao
通讯作者：
Xin Gao
影响因子：
3.8
作者：
Ballestri S;Nascimbeni F;Baldelli E;Marrazzo A;Romagnoli D;Lonardo A
通讯作者：
Lonardo A
影响因子：
24
作者：
Coutinho, Thais;Goel, Kashish;Lopez-Jimenez, Francisco
通讯作者：
Lopez-Jimenez, Francisco
影响因子：
12.6
作者：
Fracanzani, Anna Ludovica;Petta, Salvatore;Fargion, Silvia
通讯作者：
Fargion, Silvia
影响因子：
6.7
作者：
Lin，Huapeng;Wong，Grace L-H;Wong，Vincent W-S
通讯作者：
Wong，Vincent W-S