| Background:Being one of three most common death causes in the world, cerebrovascular disease is severely threatening people's life nowadays. The etiology is extremely complex and caused by a number of environmental and genetic factors together. Of the environmental reasons, high blood pressure,diabetes, heart disease, high blood fat, atherosclerosis and abnormal blood composition are risks for this disease, and these symptoms are associated with the genetic conditions as well. SREBP belongs to the family of nuclear transcription factors, regulating the genes responsible for cholesterol and fat synthesis.Mutations of SREBP gene is closely implicated in dyslipidemia and formation of atherosclerosis. Controlled by related genes, apoptosis is also known as programmed cell death,which plays a pivotal role in maintaining normal physiological functions and homeostasis of cell and body. Apoptosis is induced by the interaction between Fas and its intrinsic ligand FasL. It is showed that apoptosis is of importance in developing atherosclerosis and accounts for the cerebral hemorrhage-induced injuries.At present, little is known about the relationship between Sterol regulatory element binding protein (SREBP) gene, Fas/FasL gene polymorphisms and cerebral infarction as well as cerebral hemorrhage disease susceptibility. Changes of sFas and sFasL in blood plasma in different stages of cerebral infarction and cerebral hemorrhage also deserve further investigation.Purpose(1)To understand the distribution of SREBP Fas/FasL genetic polymorphism in the Han nationality of Hunan.(2) To investigate the relationship between SREBP Fas/FasL genetic polymorphism and cerebral infarction,cerebral hemorrhage.. (3)To elucidate the relationship between plasma levels of sFasL and sFas and cerebral infarction and cerebral hemorrhage.MethodsFrom September 2007 to September 2009,patients with cerebral infarction 246 were randomly selected, including 164 males and 82 females, the average age was 62.24±9.43 years.142 hemorrhage patients, including 91 men and 51 women cases, respectively; the average age was 59.46±9.96.155 cases with no cerebrovascular disease were in control, including 97 men and 58 women, the average age was 60.92±8.79.All participants were from Hunan Province, there were no difference in age and gender among these groups.Genomic DNA of peripheral leukocytes was extracted by the classical Proteinase K digestion and precipitated by saturated phenol/chloroform. Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) analysis was employed to search the genotypes in 54G>C of SREBP-1c gene,1784G>C of SREBP-2,670A>G of Fas gene,1377G>A of Fas gene and 844T>C of FasL gene, followed by detecting sFas and sFasL secretion levels with ELISA.Genotype, allele and haplotype frequencies in the cerebral infarction, the cerebral hemorrhage and the control groups were analyzed. The dynamic changes of the sFas and sFasL secretion between cerebral infarction and cerebral hemorrhage group and control group were compared.Results:(1)In all testing crowd SREBP-1c gene loci,there were three genotype GG/GC/CC and two alleles Q C.The frequency of three genotype in cerebral infarction and cerebral hemorrhage and control group were 0.492 /0.378/0.130,0.585/0.366/0.049,0.503/0.381/0.116, respectively; with G and C allele frequency 0.681/0.319,0.768/0.232,0.694/0.306.SREBP-1c gene loci genotypes frequency in the cerebral infarction and comparison was not statistically distribution different (x2=0.175,p=0.916), allele frequency between the two groups in statistical distribution was not different (χ2=0.141,p=0.707) too. Hemorrhage and statistical distribution between the two groups had no difference(χ2=4.877 p=0.087),allele frequency distribution between the two groups was statistically different (χ2=4.114,p=0.047).(2)There were three genotype GG/GC/CC and G, C two alleles in SREBP-2 1784G>C sites, three genotype in cerebral infarction and cerebral hemorrhage and control group of frequency were 0.451/0.463/0.085,0.479/0.479/0.042,0.561/0.400/0.039, respectively and G and C allele frequency were 0.683/0.317,0.718/0.282,0.761/0.239 respectively. SREBP-2 gene 1784G> C sites each genotype distribution frequency in a cerebral infarction and comparison was statistically difference(χ2=6.279,p=0.043),allele frequency between the two groups was statistically different (χ2=5.710,p=0.017)too.SREBP-2 gene 1784G>C loci in the gene frequencies between the two groups was not statistically distribution different (χ2=2.041,p=0.36), allele frequency between the two groups in statistical distribution was not different(χ2=1.426, p=0.232) either.(3)Fas 670A>G gene locus three genotype AA/AG/GG and two alleles A, G, three genotype in cerebral infarction and cerebral hemorrhage and control group of frequency were 0.207/0.610/0.183,0.239/0.577/0.183, 0.258/0.697/0.045.A and G, frequency were 0.510/0.490, 0.528/0.472,0.606/0.394 respectively. Fas gene 670A>G locus each genotype frequency in a cerebral infarction and comparison was statistically distribution different(χ2=16.115,p=0.000),allele frequency between the two groups in statistical distribution was different (χ2=7.100,p=0.008).Fas gene 670A>G locus each genotypes in cerebral hemorrhage and controlled frequency distribution was statistically different (χ2=14.442,p=0.001),frequency of alleles between the two groups was not statistically distribution different (χ2=3.704, p=0.054). Considering the body-mass index, smoking history, drinking history, history of hypertension, history of hyperlipidemia and the history of diabetes, Fas670A>G polymorphic loci increased risk of cerebral infarction and cerebral hemorrhage.(4) Fas1377G>A gene locus three genotype AA/AG/GG and two alleles A/G in cerebral infarction and cerebral hemorrhage and control group of frequency 0.301/0.675/0.024,0.254/0.640/0.106 and 0.271/0.716/0.013 respectively, A and G frequency were 0.638/0.362,0.574/0.426, 0.629/0.371 respectively. Fas gene 1377G>A locus genotype frequencies distribution in the cerebral infarction and control groups was not statistically different(χ2=1.157, p=0.561),allele frequency distribution between the two groups was no statistical difference either (χ2=0.069, p=0.793).Fas gene 1377G>A locus gene frequencies in the cerebral hemorrhage and control groups was statistically distribution different (χ2=11.837,p=0.003).Allele frequency distribution between the two groups was no statistical difference (χ2=1.878,p=0.171).Considering the body-mass index, smoking history, drinking history, history of hypertension, hyperlipidemia history of diabetes, based on the 1377G/Fas-A polymorphic loci that increased risk of hemorrhage.(5)FasL gene loci 844T>C three genotype TT/TC/CC and two alleles T, C,three genotype in cerebral infarction group and control group of frequency 0.016/0.476/0.508,0.013/0.510/0.477 respectively. T and allele C frequency were 0.254/0.746,0.268/0.732 respectively. There were no TT gengtype in cerebral hemorrhage group.TC and CC the frequency were 0.493/0.507 respectively. T and C allele frequency were 0.246/0.754 respectively. FasL gene 844T>C loci the gene frequency distribution in cerebral infarction and control groups was not statistically different (χ2=0.478,p=0.787),allele frequency between the two groups was not statistically different (χ2=0.185,p=0.667) either. FasL gene 844T>C loci the gene frequencies distribution in cerebral and control groups was not statistically different(χ2=2.006,p=0.367).Allele frequency distribution between the two groups was not in statistical difference (χ2=0.350, p=0.554).(6)Two SNP locis in Fas gene composed four haplotypes A670-G1377, A670-A1377, G670-G1377 and G670-A1377. frequency of four haplotypes in the cerebral infarction group was 0.204-.0.308,0.158 and 0.330 respectively. The frequency of the four haplotypes in the cerebral hemorrhage group were 0.261,0.268,0.306 and 0.165 respectively. In the control the frequency were 0.312 0.294,0.059 and 0.335 respectively. Four haplotypes in the cerebral infarction and analysis of the control group was significant different(χ2=24.748,p<0.001),cerebral infarction G670 group G1377 has a significantly higher frequency than the control (χ2=17.679,p<0.001,OR=2.994),cerebral infarction A670 group G1377 had different frequency between cerebral infarction and control group(x2=11.999,p<0.001).Four haplotypes in the cerebral blood group and control group was significant different (χ2=17.401,p<0.001), G670-G1377 frequency in case group was significantly higher than control group(χ2=17.180,p<0.001,OR=3.164).(7) sFas secretion in acute cerebral infarction and recovery period cases markedly higher than control group (p<0.05), During the acute cerebral hemorrhage period the case group had significantly higher level of sFas secretion than the control group (p<0.05).The more serious of these disease, the higher of sFas.SFasL secretion levels in cerebral infarction and cerebral hemorrhage had no obvious different with the control group.(8) sFas and sFasl secretion levels of GG genotype individuals was significantly higher than the AA and AG genotype individuals in Fas gene 670 A>G polymorphic loci,with significant difference.However, there wasn't significant differences among the various genotypes individuals in Fas 1377G>A and FasL 844T>C polymorphic locus.Conclusion:(1)SREBP-lc gene> 54G/C genetic polymorphism may be not associated with cerebral infarction and cerebral hemorrhage in Hunan Han population.(2) SREBP-2 gene 1784G>C genetic polymorphism may be related to cerebral infarction while irrelevant to cerebral hemorrhage in Hunan Han population.(3) In Hunan Han population, Fas gene 670 A>G genetic polymorphism may be associated with cerebral infarction while Fas gene 1377G>A and FasL gene 844T>C polymorphism may be irrelevant to cerebral infarction. Fas gene 670 A>G and 1377G>A genetic polymorphism may be associated with cerebral hemorrhage while FasL gene 844T>C polymorphism may be irrelevant to cerebral hemorrhage.(4) The Haplotype G670-G1377 in Fas gene is likely to increase cerebral infarction and cerebral hemorrhage in Hunan Han population..(5)In the acute and recovery stages, total Fas secretion of the cerebral infarction group is markedly increased and sFas rising is proportional with the severity of the illness. The difference was associated with Fas670/G polymorphism.
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