The Preliminary Screening Of TGFB2、TGFBR2 And ACTA2 Mutations In Patients With Sporadic Thoracic Aortic Aneurysm And Dissection

Background and objective:Thoracic aortic aneurysm and dissection(TAAD) is a common disease in clinical work, displaying a dilated aorta. It have diverse and complex pathogenic factors and demonstrate significant mortality during the acute phase, approximately20% of cases have a genetic predisposition. Recently, more and more researchers focus on the relationship between the pathogenesis of TAAD and associative gene mutations, especially mutations in several genes such as ACTA2, TGFB2 and TGFBR2. ACTA2 encodes vessel smooth muscle cell alpha-actin,whereas TGFB2 and TGFBR2, coming from transforming growth factor-β(TGF-β)signal pathway,encode ligand and receptor respectively. In order to identify more mutations of ACTA2,TGFB2 and TGFBR2,we utilized blood and abnormal tissue sample to screen the target genes, collected from the patients with sporadic thoracic aortic aneurysm and dissection(STAAD), and explore the differences between blood and tissue in gene mutation detection simultaneously.Metholds:After a rigorous screening, 30 patients with STAAD and 63 health individuals were involved in our research, and were divided into patient group and control group automatically. All patient came from different families with negative bloodshed. We adopted polymerase chain reaction(PCR) and direct sequencing to screen all exons of the target genes, and mapped the three-dimensional model of protein to present mutations or genetic polymorphisms by using the Pymol. Chi-squared test was performed to compare the difference between blood and tissue in gene mutation detection.Results:We identified a missense mutation of ACTA2(c.554 G>A,p. R 185 Q) in patient group, which was absent from control group. Meanwhile, we also identified a genetic polymorphisms rs2228048 of TGFBR2(c.1167 C>T,p. N 389 N). Noteworthily, the number of detection of rs2228048 in blood and abnormal tissue samples, which were derived from patient group, is five and thirteen respectively, the blood samples in control group were detected two variation as well. This two mutations were reported yet. According to the statistical analysis, the detection rates of genetic polymorphisms in blood samples between patients and controls, and the allele frequency between blood and tissue in patient group are significant differences.Conclusions:Both missense mutation of ACTA2(p. R 185 Q) and genetic polymorphisms rs2228048 of TGFBR2 may contribute to the pathogenesis of STAAD. In the aspect of mutational detection, abnormal tissue samples are superior to blood samples.