The Relationship Between -509C/T Gene Polymorphism, Plasma Concentration Of TGF-β1 And Intracranial Aneurysm

IntroductionIntracranial aneurysm(IA) are local pathological tumor samples of cerebral arterial wall.IA are potentially devastating, and due to their rapid development, pose a serious health risk characterized by the lack of medical treatment options and high rates of disability and mortality. Almost half of the IA patients died once AN broke.Many patients died before they can reach the hospital.Cranitomy and intervention embolization are the major treatments,but both of them are not perfect. Therefore, it is important for us to study the pathologic mechanism of AN and to provide novel therapy and preventive.Familial occurrence of intracranial aneurysms suggests there are genetic factors involved in the development of such diseases. Molecular genetics tell us that the gene polymorphism is the foundation of predisposition.So we try to explore the genetic clues of AN through SNP analysis.TGF-?1 is a member of a supperfamily of ligands and receptors that include the TGF-?1,2,3, bone morphogenetic proteins, and the activins/inhibins,et,al. These growth factors participate in a wide array of cellular responses including: proliferation, angiogenesis, differentiation, apoptosis, inflammation, and wound healing. Recent researches showed that AN develop as a result of maladaptive remodeling of the vascular extracellular matrix(ECM).And TGF-?1 was considered to play a important role in vascular remodeling. Genetic linkage analysis indicate us that the 19q13 area(TGF-?1 encoding area)may be candidate susceptibility locus for AN. So we speculate that TGF-?1 is associated with AN.-509C/T is one SNP of TGF-?1 gene,and the function and meaning of the SNP is not so clear.There are some researches reported that TGF-?1 gene -509C/T polymorphism can regulate the plasma level of TGF-?1. Our research was to detect the frequencies of TGF-?1-509 in Han people and to clarify the relationship among TGF-?1-509 gene polymorphism, plasma level of TGF-?1, and intracranial AN.PartⅠThe association between polymorphism of TGF-?1 gene-509C/T and intracranial aneurysmObjectiveTo explore the relationship between TGF-?1 gene polymorphism of -509C/T, and the risk of cerebral aneurysm by detecting the frequencies of TGF-?1-509C/T allele genotypes.Methods80 cases of IA confirmed by DSA and 181 control subjects excluded IA by MRA and DSA were selected. Peripheral vein blood was drawn from every subject. Polymerase chain reaction-restriction fragment length polymorphism technique was used to detect -509C/T polymorphism of the TGF-?1 gene. ResultsThe frequencies of the TT,CT,and CC genotype and T allele gene of both groups had no significantly differences (P<0.05). There were no significant differences in the frequenceies of TGF-β1 -509C/TConclusionOur study suggests that TGF-?1 gene polymorphism at -509C/T is not associated with the IA. Polymorphism at -509C/T may be not an independent risk factor for IA.PartⅡThe relationship between plasma concentration of TGF-?1 ,IA , and its gene PolymorphisminObjectiveTo study the relationship between TGF-?1 plasma concentration and IA,and analyze the plasma level of TGF-?1 in different genotype to explore the relationship between polymorphism of -509C/T and TGF-?1 expression.Methods80 cases of IA confirmed by DSA and 181 control subjects excluded IA by MRA and DSA were selected. And the peripheral vein blood samples were collected from them to gain the plasma.Double-antibody enzyme-linked immunosorbent assay was used to detect the concentration of TGF-?1 in plasma.ResultsThe plasma concentration of TGF-?1 was higher in IA group than in control group.(P<0.05).The plasma level of TGF-?1 in different genotype of IA group had no significant difference(P>0.05);And the plasma level of TGF-?1 in different genotype of control group also had no significant difference(P>0.05).ConclusionHigher plasma level of TGF-?1 may be associated with IA,TGF-?1 may play a important role during IA formation and rupture mechanism.There was no association between polymorphism of -509C/T and the plasma level of TGF-?1 in our research,indicated that the plasma level of TGF-?1 may be affected by many other factors.