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中国汉族人群中PPARα/γ基因多态性与脂蛋白(a)的相关性分析。

Analysis on the association between PPARα/γ polymorphisms and lipoprotein(a) in a Chinese Han population.

作者信息

Xie Hui-Jian, Hai Bo, Wu Ming, Chen Qiu, Liu Meng-Meng, Dong Chen, Guo Zhi-Rong

机构信息

Department of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Ren'ai Road, Industrial Park District, Suzhou, 215123, Jiangsu, China.

出版信息

Mol Genet Genomics. 2014 Oct;289(5):981-7. doi: 10.1007/s00438-014-0866-9. Epub 2014 Jun 1.

Abstract

Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle, is recognized as an independent risk factor for atherosclerosis, cardiovascular diseases, and diabetic vascular diseases. Our recent studies revealed that the single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors (PPARα/δ/γ) gene are involved in the regulation of lipid storage and metabolism. In order to investigate the relationships between the SNPs of PPARα/γ gene and plasma levels of Lp(a), 644 participants were randomly selected from Chinese Han population in the present study. As the results shown, Lp(a) was significantly associated with L162V (rs1800206) in PPARα. Compared with those subjects with widetype (LL), significantly higher Lp(a) concentration was determined in the individuals with mutant (LV + VV) (mean difference: 49.07 mg/l, 95% CI 23.32-74.82 mg/l, p = 0.0002). Moreover, with generalized multifactor dimensionality reduction analysis, our present results indicated that there was a significant association between plasma Lp(a) level and gene-gene interaction among the polymorphisms rs1800206, rs135539 in PPARα and rs10865710, rs1805192, and rs4684847 in PPARγ. Therefore, our presented study indicated that PPARα/γ polymorphisms should be involved in the regulation of plasma Lp(a) in independently and/or in an interactive manner, suggesting that PPARα/γ gene may influence the risk of hypertension, cardiovascular diseases, and dyslipidemia by regulating Lp(a) level.

摘要

脂蛋白(a)[Lp(a)]是一种低密度脂蛋白样颗粒,被认为是动脉粥样硬化、心血管疾病和糖尿病血管疾病的独立危险因素。我们最近的研究表明,过氧化物酶体增殖物激活受体(PPARα/δ/γ)基因的单核苷酸多态性(SNPs)参与脂质储存和代谢的调节。为了研究PPARα/γ基因的SNPs与血浆Lp(a)水平之间的关系,本研究从中国汉族人群中随机选取了644名参与者。结果显示,Lp(a)与PPARα中的L162V(rs1800206)显著相关。与野生型(LL)受试者相比,突变型(LV+VV)个体的Lp(a)浓度显著更高(平均差异:49.07mg/l,95%CI 23.32-74.82mg/l,p=0.0002)。此外,通过广义多因素降维分析,我们目前的结果表明,血浆Lp(a)水平与PPARα中的多态性rs1800206、rs135539以及PPARγ中的rs10865710、rs1805192和rs46,84847之间的基因-基因相互作用存在显著关联。因此,我们目前的研究表明,PPARα/γ多态性应独立和/或以交互方式参与血浆Lp(a)的调节,提示PPARα/γ基因可能通过调节Lp(a)水平影响高血压、心血管疾病和血脂异常的风险。

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