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TGF-β 受体基因单核苷酸多态性与腹主动脉瘤关联性的荟萃分析

Meta-analysis of the association between single nucleotide polymorphisms in TGF-β receptor genes and abdominal aortic aneurysm.

机构信息

Vascular Biology Unit, School of Medicine, James Cook University, Townsville, Queensland 4811, Australia.

出版信息

Atherosclerosis. 2011 Nov;219(1):218-23. doi: 10.1016/j.atherosclerosis.2011.07.105. Epub 2011 Jul 30.

Abstract

OBJECTIVE

The role of transforming growth factor (TGF)-beta in abdominal aortic aneurysm (AAA) is controversial. The aim of this study was to assess the association of single nucleotide polymorphisms (SNPs) within TGFBR1 and TGFBR2 with AAA and infrarenal aortic diameter by combining data from previously published studies.

METHODS

We performed a meta-analysis using individual subject data from three independent case-control groups from Western Australia (n=1675), New Zealand (n=1209), and the Netherlands (n=1636) with 610, 601, and 693 cases of AAA (maximum infrarenal aortic diameter ≥30 mm), respectively. Data were available for two TGFBR1 (rs10819634, rs1571590) and six TGFBR2 (rs304839, rs1346907, rs1036095, rs9831477, rs9843143, rs764522) SNPs.

RESULTS

There was marked heterogeneity between studies. The G alleles of the TGFBR2 rs764522 and rs1036095 SNPs were associated with AAA under a recessive model (OR=1.69, 95% CI 1.28-2.25, P<0.001 and OR=1.59, 95% CI 1.23-2.07, P<0.001) when a fixed effects model was used. Both associations remained significant after adjustment for multiple testing.

CONCLUSION

This study suggests that two common genetic polymorphisms in TGFBR2 are associated with the risk of developing AAA although this association was mainly driven by findings in the Netherlands group and marked between study heterogeneity was detected.

摘要

目的

转化生长因子-β(TGF-β)在腹主动脉瘤(AAA)中的作用存在争议。本研究旨在通过合并先前发表的研究中的数据,评估 TGFBR1 和 TGFBR2 内的单核苷酸多态性(SNP)与 AAA 和肾下主动脉直径的相关性。

方法

我们对来自澳大利亚西部(n=1675)、新西兰(n=1209)和荷兰(n=1636)的三个独立病例对照组的个体受试者数据进行了荟萃分析,每组分别有 610、601 和 693 例 AAA(最大肾下主动脉直径≥30mm)。可获得 TGFBR1(rs10819634,rs1571590)和 TGFBR2(rs304839,rs1346907,rs1036095,rs9831477,rs9843143,rs764522)的两个和六个 SNP 的数据。

结果

研究之间存在明显的异质性。在隐性模型下,TGFBR2 的 rs764522 和 rs1036095 SNP 的 G 等位基因与 AAA 相关(OR=1.69,95%CI 1.28-2.25,P<0.001 和 OR=1.59,95%CI 1.23-2.07,P<0.001),当使用固定效应模型时。在进行多次检验调整后,这两个关联仍然具有统计学意义。

结论

本研究表明,TGFBR2 中的两个常见遗传多态性与 AAA 的发病风险相关,尽管这种关联主要由荷兰组的发现驱动,并且检测到明显的研究间异质性。

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