载脂蛋白E、载脂蛋白AI、载脂蛋白CIII、载脂蛋白B、脂蛋白脂肪酶（LPL）和肝脂肪酶（LIPC）基因常见变异与冠状动脉疾病（CAD）的遗传学研究：LIPC基因变异与已确诊CAD患者的临床结局相关。
Genetic study of common variants at the Apo E, Apo AI, Apo CIII, Apo B, lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes and coronary artery disease (CAD): variation in LIPC gene associates with clinical outcomes in patients with established CAD.
作者信息
Baroni Marco G, Berni Andrea, Romeo Stefano, Arca Marcello, Tesorio Tullio, Sorropago Giovanni, Di Mario Umberto, Galton David J
机构信息
Department of Clinical Sciences, Division of Endocrinology, University of Rome La Sapienza, Italy.
出版信息
BMC Med Genet. 2003 Sep 10;4:8. doi: 10.1186/1471-2350-4-8.
BACKGROUND
Current evidence demonstrates that positive family history and several alterations in lipid metabolism are all important risk factors for coronary artery disease (CAD). All lipid abnormalities themselves have genetic determinants. Thus, objective of this study was to determine whether 6 genetic variants potentially related to altered lipid metabolism were associated with CAD and with lipid abnormalities in an Italian population. These genetic variables were: apolipoprotein E (Apo E), Apo AI, Apo CIII, Apo B, lipoprotein lipase (LPL) and the hepatic lipase (LIPC) genes. Furthermore, an 8 years prospective analysis of clinical cardiovascular events was related to the various genetic markers.
METHODS
102 subjects with established coronary artery disease and 104 unrelated normal subjects were studied. CAD Patients were followed up for 8 years, and clinical CAD outcomes (a second coronary angioplasty (PTCA), myocardial infarction, coronary artery by-pass graft (CABG), cardiovascular deaths), available from 60 subjects, were related to the genetic variants by multiple regression analysis. Results. Of the six lipid loci studied (for a total of 11 polymorphisms) only the apolipoprotein E, Apo B and LIPC polymorphisms distinguished between case and controls. However, multivariate analysis accounting for clinical and metabolic predictors of CAD showed that only the ApoB Xba1 and ApoE4 polymorphism associated with CAD in this Italian population. When lipid parameters were related to genotypes, the ApoE, ApoB, and LIPC gene polymorphisms were associated to various markers of dyslipidaemia in the CAD patients, confirming previous reports. When the occurrence of a second cardiovascular event was related to genotypes, an independent role was observed for the LIPC gene T202T variant.
CONCLUSIONS
variation in LIPC (hepatic lipase) gene associates with clinical outcomes in Italian patients with established CAD. Further studies on the LIPC gene in CAD patients are warranted, in particular looking at the possible influences on clinical outcomes.
背景
当前证据表明，家族史阳性以及脂质代谢的多种改变均是冠状动脉疾病（CAD）的重要危险因素。所有脂质异常本身都有遗传决定因素。因此，本研究的目的是确定6种可能与脂质代谢改变相关的基因变异是否与意大利人群中的CAD及脂质异常有关。这些基因变量包括：载脂蛋白E（Apo E）、载脂蛋白AI、载脂蛋白CIII、载脂蛋白B、脂蛋白脂肪酶（LPL）和肝脂肪酶（LIPC）基因。此外，对临床心血管事件进行了为期8年的前瞻性分析，并将其与各种基因标记相关联。
方法
对102例确诊为冠状动脉疾病的患者和104例无关的正常受试者进行了研究。对CAD患者进行了8年的随访，并通过多元回归分析将60例受试者的临床CAD结局（二次冠状动脉血管成形术（PTCA）、心肌梗死、冠状动脉搭桥术（CABG）、心血管死亡）与基因变异相关联。结果。在所研究的6个脂质位点（共11种多态性）中，只有载脂蛋白E、载脂蛋白B和LIPC多态性能够区分病例组和对照组。然而，考虑到CAD的临床和代谢预测因素的多变量分析表明，在这个意大利人群中，只有载脂蛋白B Xba1和载脂蛋白E4多态性与CAD相关。当脂质参数与基因型相关时，载脂蛋白E、载脂蛋白B和LIPC基因多态性与CAD患者血脂异常的各种标志物相关，证实了先前的报道。当第二次心血管事件的发生与基因型相关时，观察到LIPC基因T202T变异具有独立作用。
结论
LIPC（肝脂肪酶）基因变异与意大利确诊CAD患者的临床结局相关。有必要对CAD患者的LIPC基因进行进一步研究，特别是研究其对临床结局的可能影响。
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