Association Between Polymorphism Of SMAD3 Gene And Risk Of Sporadic Intracranial Arterial Aneurysms

BackgroudIntracranialarterialaneurysms(IAAs)are the anomaly bulging areas of the cerebral arteries.In most cases,there are no symptoms in the patients of IAAs.However,the subarachnoid hemorrhage(SAH)can be the very serious result of the rupture of IAAs.Researches have already showed that lots of people who are living with the IAAs need the long-term healthcare and psychological care.Therefore,the IAAs have become a social problem.The etiopathogenesis of the IAA is quite sophisticated and not totally undertood to date.The vascular inflammation takes part in the occurrence of IAAs according to the studies.TGF-?(transforming growth factor-?)belongs to the cytokines and researches have revealed that theTGF-? signal pathway plays an essential role in the pathogenesis of IAAs.It is well-known that SMAD(mothers against decapentaplegic homolog)regulates the classical TGF-? signaling pathway through modulating the genetic transcription in the cell nucleus.The SMAD3 coded by the SMAD3 gene,among all the SMAD proteins,has significant influences upon the expression of collagen,deposition of extracellular matrix and fibrosis.It is demonstrated that SMAD3 is the cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms.Up to now,the genetic role of the SMAD3 in the IAAs of the Chinese Han population hasn't been studied.ObjectivesWe designed this case-control clinical study in order to find out whether the single nucleotide polymorphisms(SNPs)of SMAD3 have impact on the risk of IAAs and involve in the formation of IAAsMethodsThe experimental subjects consist of the 330 patients with IAAs and 313 patients without IAAs.Both were recruited from the people seeing doctors in Xinqiao Hospital,Third Military Medical University from December,2014 to May,2015.We selected the subjects needed through digital subtraction angiography(MRA),computed tomography angiography(CTA)or digital subtraction angiography(DSA).5ml peripheral venous blood is collected from every subject.The polymerase chain reaction-ligase detection reaction(PCR-LDR)is used to genotype the eight SNPs selected from the SMAD3 gene.Results1.The rs1065080 SNP of SMAD3 is associated with the formation of IAAs.The genotype GG in rs1065080 affects the pathogenesis of IAAs as a codominant model(GA vs GG,OR=1.433;95% CI 1.030-1.994;P=0.032).2.There are no significantly statistical differences between the group of IAAs and the controls in the ages,genders and some of the high risk factors of cerebrovascular diseases,such as hypertention,diabetes,smoking and alcohol intake.3.The locations of the IAAs of the experimental group are as following:arteria cerebri anterior(1.77%),vertebral artery(1.77%),basilar artery(2.53%),posterior cerebral artery(6.08%),anterior communicating artery(6.08%),posterior communicating artery(8.35%),middle cerebral artery(8.86%),internal carotid artery(62.28%).4.There is so statistically significant differences in the allele frequencies between the group of IAAs and the controls.Conclusions1.The SMAD3 SNPs(rs12102171,rs4776338,rs8028147,rs36222034,rs16950635,rs11633026 and rs11636161)are notstatistically associated with the risk of IAAs.2.The rs1065080 of SMAD3 SNP is associated with the pathogenesis of IAAs.SMAD3 could play a role in the formation of Intracranialarterialaneurysms.This results may provide an innovative point of view to the screening patients with high risk factors of IAAs.