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伊朗早发冠心病患者血清 ANRIL 水平低与一些常见基因 SNPs 之间的相关性。

Associations between low serum levels of ANRIL and some common gene SNPs in Iranian patients with premature coronary artery disease.

机构信息

Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Sci Rep. 2024 Jan 13;14(1):1244. doi: 10.1038/s41598-024-51715-2.

Abstract

Coronary artery disease (CAD) is the major cause of mortality in the world. Premature development of CAD can be attributed to women under 55 and men under 45. Many genetic factors play a part in premature CAD. Among them, ANRIL, a long noncoding RNA is located at the 9p21 risk locus, and its expression seems to be correlated with CAD. In the current study, premature CAD and control blood samples, with and without Type 2 Diabetes (T2D), were genotyped for six SNPs at the 9p21 locus. Additionally, ANRIL serum expression was assessed in both groups using real-time PCR. It was performed using different primers targeting exons 1, 5-6, and 19. The χ test for association, along with t-tests and ANOVA, was employed for statistical analysis. In this study, we did not find any significant correlation between premature coronary artery disease and rs10757274, rs2383206, rs2383207, rs496892, rs10757278 and rs10738605. However, a lower ANRIL expression was correlated with each SNP risk genotype. Despite the correlation between lower ANRIL expression and CAD, Type 2 diabetes was associated with higher ANRIL expression. Altogether, the correlation between ANRIL expression and the genotypes of the studied SNPs indicated that genetic variants, even those in intronic regions, affect long noncoding RNA expression levels. In conclusion, we recommend combining genetic variants with expression analysis when developing screening strategies for families with premature CAD. To prevent the devastating outcomes of CAD in young adults, it is crucial to discover noninvasive genetic-based screening tests.

摘要

冠状动脉疾病(CAD)是世界上主要的死亡原因。CAD 的过早发展可归因于 55 岁以下的女性和 45 岁以下的男性。许多遗传因素在早发性 CAD 中起作用。其中,位于 9p21 风险位点的长非编码 RNA ANRIL,其表达似乎与 CAD 相关。在目前的研究中,对有和没有 2 型糖尿病(T2D)的早发性 CAD 和对照血液样本进行了 9p21 位点的 6 个 SNP 的基因分型。此外,还使用实时 PCR 评估了两组中的 ANRIL 血清表达。使用针对外显子 1、5-6 和 19 的不同引物进行了实验。采用 χ检验进行关联分析,并结合 t 检验和 ANOVA 进行统计分析。在这项研究中,我们没有发现早发性冠状动脉疾病与 rs10757274、rs2383206、rs2383207、rs496892、rs10757278 和 rs10738605 之间存在任何显著相关性。然而,较低的 ANRIL 表达与每个 SNP 风险基因型相关。尽管 ANRIL 表达与 CAD 之间存在相关性,但 2 型糖尿病与更高的 ANRIL 表达相关。总之,ANRIL 表达与研究 SNP 基因型之间的相关性表明,遗传变异,即使是内含子区域的遗传变异,也会影响长非编码 RNA 的表达水平。总之,在制定早发性 CAD 家族的筛查策略时,我们建议将遗传变异与表达分析相结合。为了预防年轻成年人 CAD 的破坏性后果,必须发现非侵入性的基于遗传的筛查测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2246/10787829/ebbb5c6ba218/41598_2024_51715_Fig1_HTML.jpg

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