Patatin-like phospholipase domain containing 3 variants differentially impact metabolic traits in individuals at high risk for cardiovascular events.
Patatin-like phospholipase domain containing 3 variants differentially impact metabolic traits in individuals at high risk for cardiovascular events.
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DOI：
10.1002/hep4.1183
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发表时间：
2018-07
影响因子：
5.1
通讯作者：
Lange CM
中科院分区：
文献类型：
--
作者：
Rüschenbaum S;Schwarzkopf K;Friedrich-Rust M;Seeger F;Schoelzel F;Martinez Y;Zeuzem S;Bojunga J;Lange CM
PNPLA3 （patatin - like phospolipase domain containing 3）基因的单核苷酸多态性（SNP） rs738409 C>G导致PNPLA3的I148M位置氨基酸从异亮氨酸交换为蛋氨酸。这种功能缺失突变的表达导致肝细胞甘油三酯水解受损，并与肝脂肪变性、纤维化和肝细胞癌的发生有关。与这些已建立的关联相反，PNPLA3 rs738409变异与其他代谢性状的关系尚不完全清楚。因此，我们在一项前瞻性研究中评估了PNPLA3 rs738409基因型与相关代谢特征的相关性，该研究针对心血管事件高风险患者，即接受冠状动脉造影的患者。在总共270例患者中，证实了PNPLA3 rs738409 GG基因型与非酒精性脂肪性肝炎和肝纤维化的已知关联。此外，我们发现PNPLA3 rs738409g等位基因与糖尿病存在关联（CC、CG和GG基因型分别为22%、28%和58%，P = 0.02）。与非酒精性脂肪性肝病、肝纤维化和糖尿病的相关性相反，PNPLA3 rs738409的次要G等位基因与血清总胆固醇和低密度脂蛋白血清水平呈负相关（P = 0.003和P = 0.02）。最后，PNPLA3 rs738409g等位基因的存在与显著的冠心病之间存在负相关的趋势。跨膜6超家族成员2 (TM6SF2) 167 K变异也有类似的趋势，但样本量太小，无法评估这种罕见的变异。结论：PNPLA3 rs738409 G等位基因与肝脏疾病相关，但也与相对良性的心血管风险相关。（肝病通讯2018；2:798‐806）
Single nucleotide polymorphism (SNP) rs738409 C>G in the patatin‐like phospholipase domain containing 3 (PNPLA3) gene results in an amino acid exchange from isoleucin to methionine at position I148M of PNPLA3. The expression of this loss‐of‐function mutation leads to impaired hepatocellular triglyceride hydrolysis and is associated with the development of liver steatosis, fibrosis, and hepatocellular carcinoma. In contrast to these well‐established associations, the relationship of the PNPLA3 rs738409 variant with other metabolic traits is incompletely understood. We therefore assessed the association of the PNPLA3 rs738409 genotype with relevant metabolic traits in a prospective study of patients at high risk for cardiovascular events, i.e., patients undergoing coronary angiography. In a total of 270 patients, known associations of the PNPLA3 rs738409 GG genotype with nonalcoholic steatohepatitis and liver fibrosis were confirmed. In addition, we found an association of the PNPLA3 rs738409 G allele with the presence of diabetes (22% versus 28% versus 58% for CC versus CG versus GG genotype, respectively; P = 0.02). In contrast to its association with nonalcoholic fatty liver disease, liver fibrosis, and diabetes, the minor G allele of PNPLA3 rs738409 was inversely associated with total serum cholesterol and low‐density lipoprotein serum levels (P = 0.003 and P = 0.02, respectively). Finally, there was a trend toward an inverse association between the presence of the PNPLA3 rs738409 G allele and significant coronary heart disease. Comparable trends were observed for the transmembrane 6 superfamily member 2 (TM6SF2) 167 K variant, but the sample size was too small to evaluate this rarer variant. Conclusion: The PNPLA3 rs738409 G allele is associated with liver disease but also with a relatively benign cardiovascular risk profile. (Hepatology Communications 2018;2:798‐806)
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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.
影响因子：
3.7
作者：
Petta S;Valenti L;Marchesini G;Di Marco V;Licata A;Cammà C;Barcellona MR;Cabibi D;Donati B;Fracanzani A;Grimaudo S;Parrinello G;Pipitone RM;Torres D;Fargion S;Licata G;Craxì A
通讯作者：
Craxì A
影响因子：
4.5
作者：
Speliotes EK;Yerges-Armstrong LM;Wu J;Hernaez R;Kim LJ;Palmer CD;Gudnason V;Eiriksdottir G;Garcia ME;Launer LJ;Nalls MA;Clark JM;Mitchell BD;Shuldiner AR;Butler JL;Tomas M;Hoffmann U;Hwang SJ;Massaro JM;O'Donnell CJ;Sahani DV;Salomaa V;Schadt EE;Schwartz SM;Siscovick DS;NASH CRN;GIANT Consortium;MAGIC Investigators;Voight BF;Carr JJ;Feitosa MF;Harris TB;Fox CS;Smith AV;Kao WH;Hirschhorn JN;Borecki IB;GOLD Consortium
通讯作者：
GOLD Consortium
影响因子：
25.7
作者：
Dubuquoy, Celine;Robichon, Celine;Moldes, Marthe
通讯作者：
Moldes, Marthe
影响因子：
29.4
作者：
Mancina RM;Dongiovanni P;Petta S;Pingitore P;Meroni M;Rametta R;Borén J;Montalcini T;Pujia A;Wiklund O;Hindy G;Spagnuolo R;Motta BM;Pipitone RM;Craxì A;Fargion S;Nobili V;Käkelä P;Kärjä V;Männistö V;Pihlajamäki J;Reilly DF;Castro-Perez J;Kozlitina J;Valenti L;Romeo S
通讯作者：
Romeo S