Analysis Of TGFB1Single Nucleotide Polymorphisms In Moyamoya Disease

Moyamoya disease is a severe cerebral vascular disease, with the mainpathological characteristics of the spontaneous progression of carotid artery stenoticand neovascular networks formation. With the progress of vascular stenosis andocclusion, the brain blood flow of the distribution area decreases and it causescerebral hypoperfusion, at last severe cerebral infarction will happen. When theischemia becomes severer, weak compensatory vascular network is graduallyexpanded, or small aneurysms form, due to impact of blood flow the vascular wallwill be ruptured and lead to cerebral hemorrhage. Cerebral hemorrhage and cerebralischemia are the disease's two most important clinical manifestations. The onset of thedisease will lead to catastrophic neurological dysfunction, morbidity and highmortality, therefore the study of etiology of the disease diagnosis and treatment is ofgreat significance. Moyamoya disease was once considered as acquired disease due toenvironmental factors changes, but with the development of research, scientistscurrently believe genetics play an important role in the process of Moyamoya disease.Moyamoya disease in the Asian population has significantly high incidence, and has afamilial aggregation as cited in epidemiological reports, female patients are moresignificantly frequent than male patients, adolescence is an important diseaseoccurrence peak age, but there is no enough evidence to support the disease is relatedwith the presence of sex chromosome, and familial Moyamoya disease pedigreesinvestigation is not consistent with the Mendel inheritance. In recent years manyscientific reports demonstrate that there are multiple loci closely related to the disease,but so far there is no clear gene can explain the occurrence of disease alone, so thedisease is generally considered as a polygenic disease of multifactorial etiology. Many factors involved in the regulation of cell proliferation and differentiation are proved tobe associated with the disease. Compensatory vascular network formation indicatesspecial molecular background in the progress of Moyamoya disease, particularlyinvolved in many important angiogenic factors. Transforming growth factor B1(TGFB1) is an important regulatory cytokine for cell growth and angiogenesis, andthe factor has significant high expression in the tissue samples and plasma of patients.Single nucleotide polymorphism (SNP) as a molecular tag of new generation,canfacilitate the discovery and identification of disease between patients and controls,and changed disease progress through the synthesis of amino acids. This research wasfocused on the analysis of the TGFB1exon1polymorphisms in Moyamoya disease.This study recruited41European sporadic patients confirmed of the diagnosis ofMoyamoya disease and68healthy control group members. DNAs were extractedfrom blood samples. Polymerase chain reaction amplification of TGFB1exon1of allgene sequence was performed, the sequencing of PCR products resulted to reveal4different single nucleotide polymorphisms. SNPrs1800470had been reported to havesignificant difference between the disease group and control group, but our statisticalanalysis could not get the similar significant conclusions. In SNPrs1800471andSNPrs56281462, there is no evidence of statistical difference. A new discovery ofpolymorphism of SNPIVS1+13intron, not yet reported, also had no association withthe disease. Our results excluded the transforming growth factor B1exon1polymorphisms as risk factors for Moyamoya disease. But in East Asian the diseasehas high incidence and familial aggregative feature, our patient cohort was from theEuropeans and relatively a small size, so it is necessary to repeat the experiment andverify our conclusions by further research in Asian people, familial cases, and largedisease group. The exon1of TGFB1has an important role for transcription initiation,but TGFB1has7exons, our study didn't involve the other6additional exons, so itneeds more discussion. To date, this is largest cohort in European Moyamoya patients.