PNPLA3 GG genotype and carotid atherosclerosis in patients with non-alcoholic fatty liver disease.
PNPLA3 GG genotype and carotid atherosclerosis in patients with non-alcoholic fatty liver disease.
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DOI：
10.1371/journal.pone.0074089
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发表时间：
2013
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;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
评估NAFLD患者颈动脉粥样硬化的存在是否与影响肝脏脂肪蓄积和肝损伤严重程度的基因变异相关。我们记录了162例连续的、经活检证实的西西里NAFLD患者的人体测量、代谢和组织学数据（Kleiner评分）。超声检查颈动脉内膜中层厚度（IMT）、IMT增厚（IMT≥1 mm）和颈动脉斑块（颈总动脉水平局灶性增厚> 1.3mm）。还评估了IL 28 B rs 12979860 C>T、PNPLA 3 rs738409 C>G、GCKR rs780094 C>T、LYPLAL 1 rs 12137855 C>T和NCAN rs 2228603 C>T单核苷酸多态性。该结果在来自北方意大利的267名临床或组织学诊断为NAFLD的受试者中得到验证，其中63人进行了随访检查。两个队列的颈动脉斑块、IMT增厚和平均最大IMT相似，而西西里队列的糖尿病、肥胖、NASH和PNPLA 3 GG多态性的患病率（21%vs.13%，p = 0.02）显著较高。 在该队列中，PNPLA 3 GG基因型颈动脉斑块和IMT增厚的患病率高于CC/CG基因型（分别为53%vs.32%，p = 0.02; 62%vs.28%，p<0.001）。 这些关联在多变量分析中得到证实（OR 2.94; 95% C. I. 1.12-7.71，p = 0.02，OR 4.11; 95% CI。 1.69-9.96，p = 0.002），尽管仅在<50岁的患者中观察到。 同样在验证队列中，PNPLA 3 GG基因型仅与年轻患者的IMT增厚独立相关（OR：6.00，95% CI 1.36-29，p = 0.01）和随访检查患者的IMT进展（p = 0.05）。 PNPLA 3 GG基因型与年轻NAFLD患者颈动脉粥样硬化严重程度相关。这种关联的机制及其临床意义需要进一步研究。
To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results were validated in a cohort of 267 subjects with clinical or histological diagnosis of NAFLD from Northern Italy, 63 of whom had follow-up examinations. Carotid plaques, IMT thickening and mean maximum IMT were similar in the two cohorts, whereas the prevalence of diabetes, obesity, NASH, and PNPLA3 GG polymorphism(21%vs.13%, p = 0.02) were significantly higher in the Sicilian cohort. In this cohort, the prevalence of carotid plaques and IMT thickening was higher in PNPLA3 GG compared to CC/CG genotype(53%vs.32%, p = 0.02; 62%vs.28%, p<0.001, respectively). These associations were confirmed at multivariate analyses (OR2.94;95%C.I. 1.12–7.71, p = 0.02, and OR4.11;95%C.I. 1.69–9.96, p = 0.002, respectively), although have been observed only in patients <50years. Also in the validation cohort, PNPLA3 GG genotype was independently associated with IMT thickening in younger patients only (OR: 6.00,95%C.I. 1.36–29, p = 0.01), and to IMT progression (p = 0.05) in patients with follow-up examinations. PNPLA3 GG genotype is associated with higher severity of carotid atherosclerosis in younger patients with NAFLD. Mechanisms underlying this association, and its clinical relevance need further investigations.
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非酒精性脂肪肝病与冠状动脉钙化有关。
影响因子：
13.5
作者：
Kim, Donghee;Choi, Su-Yeon;Park, Eun Ha;Lee, Whal;Kang, Jin Hwa;Kim, Won;Kim, Yoon Jun;Yoon, Jung-Hwan;Jeong, Sook Hyang;Lee, Dong Ho;Lee, Hyo-suk;Larson, Joseph;Therneau, Terry M.;Kim, W. Ray
通讯作者：
Kim, W. Ray
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
DOI：
10.1161/01.atv.0000160613.57985.18
发表时间：
2005-05-01
影响因子：
8.7
作者：
Brea, A;Mosquera, D;Ros, E
通讯作者：
Ros, E
影响因子：
25.7
作者：
Colloredo, G;Guido, M;Leandro, G
通讯作者：
Leandro, G
影响因子：
5
作者：
Chambless, LE;Heiss, G;Clegg, LX
通讯作者：
Clegg, LX