CDKN2B 基因的表达受 CAD 患者 MI 后 6 个月时 9p21.3 rs10757278 的影响。

CDKN2B gene expression is affected by 9p21.3 rs10757278 in CAD patients, six months after the MI.

机构信息

VINČA Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.

Cardiology Clinic, Clinical Center of Serbia, 11000 Belgrade, Serbia.

出版信息

Clin Biochem. 2019 Nov;73:70-76. doi: 10.1016/j.clinbiochem.2019.08.003. Epub 2019 Aug 3.

DOI:10.1016/j.clinbiochem.2019.08.003

PMID:31386834

Abstract

BACKGROUND

Chromosomal region 9p21.3 is most robustly associated with coronary artery disease (CAD) in western European populations. However, heterogeneity in CAD phenotypes leads to uncertainty whether 9p21.3 is associated with stable and/or acute clinical presentations of CAD. 9p21.3 is rich in regulatory elements, but the underlying mechanisms of its actions in CAD remain unclear. We investigate the association of 9p21.3 two haplotype blocks lead variants (rs10757278 and rs518394) with first-ever non-fatal myocardial infarction (MI) in CAD patients and their association with CDKN2B mRNA expression in peripheral blood mononuclear cells 6 months after the event.

METHODS

We included CAD patients with sustained first MI (n = 523) and controls (n = 583). Gene expression was assessed in 72 patients 6 months after MI and 43 healthy controls. TaqMan® technology was used for the gene expression and genotyping analysis.

RESULTS

CDKN2B mRNA was significantly lower in MI patients compared with the controls (p = 0.002) and in patients carrying the rs10757278 G risk allele versus AA homozygotes (p = 0.012) 6 months after the event. While we confirmed the association of rs10757278 with CDKN2B expression in MI patients, we failed to find an association between the investigated variants and MI or disease burden.

CONCLUSIONS

We suggest a dysregulation of gene expression in the 9p21.3 region six months after acute MI, which is affected by a genetic variant in patients. The rs10757278 rare allele is one factor that might lead to prolonged risk for proatherogenic complications.

摘要

背景

染色体区域 9p21.3 与西欧人群的冠状动脉疾病（CAD）最为密切相关。然而，CAD 表型的异质性导致人们不确定 9p21.3 是否与 CAD 的稳定和/或急性临床表现有关。9p21.3 富含调节元件，但它在 CAD 中的作用的潜在机制仍不清楚。我们研究了 9p21.3 两个单倍型块主导变体（rs10757278 和 rs518394）与 CAD 患者首次非致命性心肌梗死（MI）的关联，以及它们与事件发生后 6 个月外周血单核细胞中 CDKN2B mRNA 表达的关联。

方法

我们纳入了 523 例持续性首次 MI 的 CAD 患者和 583 例对照者。在 MI 后 6 个月评估了 72 例患者和 43 例健康对照者的基因表达情况。采用 TaqMan®技术进行基因表达和基因分型分析。

结果

与对照组相比，MI 患者的 CDKN2B mRNA 表达显著降低（p=0.002），与携带 rs10757278 G 风险等位基因的患者相比，AA 纯合子患者的 CDKN2B mRNA 表达也显著降低（p=0.012）。尽管我们证实了 rs10757278 与 MI 患者的 CDKN2B 表达有关，但我们没有发现所研究的变异与 MI 或疾病负担之间的关联。