Department of Clinical Laboratory, Liyuan Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Human Genome Research Center, Cardio-X Institute, College of Life Science and Technology of Huazhong University of Science and Technology, Wuhan, PR China.
Aging (Albany NY). 2021 Dec 12;13(23):25393-25407. doi: 10.18632/aging.203755.
regulates activation of vascular endothelial cells, and genome-wide association studies showed that variants in confer risk to stroke. However, whether variants in are associated with coronary artery disease (CAD) is unknown.
We genotyped rs34166160 in in two independent Chinese GeneID populations which included 2,794 CAD cases and 4,131 controls, and performed genetics association studies. Functional studies were also performed to reveal the mechanisms.
Allele rs34166160 significantly confers risk to CAD in the GeneID Hubei population which contained 1,440 CAD cases and 2,660 CAD-free controls (observed = 6.39 × 10 with an odds ratio (OR) was 3.39, adjusted = 8.12 × 10 with an OR of 3.10). The association was replicated in another population, GeneID Shandong population contained 1,354 CAD cases and 1,471 controls ( = 3.33 × 10 with an OR of 3.14, = 0.01 with an OR of 2.74). After combining the two populations, the association was more significant ( = 1.57 × 10 with an OR of 3.58, = 3.41 × 10 with an OR of 2.80). In addition, we found that rs34166160 was associated with the mRNA expression level of and the flanking region of rs34166160 can directly bind with transcriptional factor CCAAT-box/enhancer-binding protein beta, and the risk A allele has more transcription activity than non-risk C allele with or without LPS in HUVEC cells.
Our study demonstrates that the functional rare variant rs34166160 in confers risk to CAD for the first time, and these findings further expand the range of the pathology of CAD and atherosclerosis.
调控血管内皮细胞的激活，全基因组关联研究表明， 中的变体与中风风险相关。然而， 中的变体是否与冠心病（CAD）相关尚不清楚。
我们在两个独立的中国GeneID 人群中对 rs34166160 进行基因分型，其中包括 2794 例 CAD 病例和 4131 例对照，并进行了遗传关联研究。还进行了功能研究以揭示机制。
等位基因 rs34166160 在包含 1440 例 CAD 病例和 2660 例 CAD 对照的 GeneID 湖北人群中显著增加 CAD 的发病风险（观察值为 6.39×10，比值比（OR）为 3.39，调整值为 8.12×10，OR 为 3.10）。该关联在另一个人群，即包含 1354 例 CAD 病例和 1471 例对照的 GeneID 山东人群中得到了复制（ = 3.33×10，OR 为 3.14， = 0.01，OR 为 2.74）。将两个人群合并后，关联更加显著（ = 1.57×10，OR 为 3.58， = 3.41×10，OR 为 2.80）。此外，我们发现 rs34166160 与 及其侧翼区域的 mRNA 表达水平相关，rs34166160 的侧翼区域可以直接与转录因子 CCAAT 框/增强子结合蛋白β结合，并且风险 A 等位基因在 HUVEC 细胞中具有比非风险 C 等位基因更高的转录活性，无论有无 LPS。
本研究首次证明了 中的功能性稀有变异 rs34166160 与 CAD 风险相关，这些发现进一步扩展了 CAD 和动脉粥样硬化的病理范围。
