The Relationship Between S100B Gene Polymorphism And Its Expression Level And Ischemic Stroke

Objective:To explore the distribution characteristics of S100 B gene rs9722,rs881827,rs9984765,rs2839356,rs1051169 and rs2186358 polymorphisms in Guangxi population,and to compare the distribution frequencies of the six SNPs in different areas.Methods:SNaPshot SNP genotyping and DNA sequencing were used to detect the genotypes of the S100 B genes rs9722,rs881827,rs9984765,rs2839356,rs1051169 and rs2186358 in 398 subjects form Guangxi population.Results:(1)The CC,CT and TT genotype frequencies of rs9722 were 49.5%,44.0% and 6.5% in Guangxi population,respectively.The C and T allele frequencies were 71.5% and 28.5%,respectively.There were significant differences in genotype and allele frequencies of rs9722 between Guangxi population and HapMap-CEU,HapMap-YRI,HapMap-JPT and HapMap-HCB population(P<0.05).(2)The CC,CT and TT genotype frequencies of rs881827 were 34.4%,48.3% and 17.3% in Guangxi population,respectively.The C and T allele frequencies were 58.5% and 41.5%,respectively.There were significant differences in genotype and allele frequencies of rs881827 between Guangxi population and HapMap-CEU,HapMap-YRI and HapMap-JPT population(P<0.05);However,however,there no significantly different from HapMap-HCB population(P>0.05).(3)The TT,CT and CC genotype frequencies of rs9984765 were 47.7%,44.5% and 7.8% in Guangxi population,respectively.The T and C allele frequencies were 56.7% and 43.3%,respectively.There were significant differences in genotype and allele frequencies ofrs9984765 between Guangxi population and HapMap-YRI,HapMap-JPT and HapMap-HCB population(P>0.05),however,there no significantly different from HapMap-CEU population(P>0.05).(4)The TT,TC and CC genotype frequencies of rs2839356 were 49.2%,43.7% and 7.1% in Guangxi population,respectively.The T and C allele requencies were 71.1% and 28.9%,respectively.There were significant differences in genotype and allele frequencies between Guangxi population and HapMap-CEU,HapMap-YRI and HapMap-JPT population(P<0.05),however,there was no significantly different from HapMap-HCB population(P>0.05).(5)The GG,GC and CC genotype frequencies of rs1051169 were 41.2%,44.7% and 14.1% in Guangxi population,respectively.The G and C allele frequencies were 63.6% and 36.4%,respectively.There were significant differences in genotype and allele frequencies of rs1051169 between Guangxi population and HapMap-CEU,HapMap-YRI and HapMap-JPT population(P<0.05);Compared with HapMap-HCB population,the allele frequencies were significantly different(P<0.05),and the genotype frequencies were not significantly different(P>0.05).(6)The AA,AC and CC genotype frequencies were 82.4%,15.8% and 1.8% of 2186358 in Guangxi population,respectively.The A and C alleles frequencies were 90.3% and 9.7%,respectively.There were significant differences in genotype and allele frequencies of rs2186358 between Guangxi population and HapMap-CEU and HapMap-YRI(P<0.05),however,there was no significant different from those of HapMap-JPT(P>0.05)).Conclusion: There are S100 B gene rs9722,rs881827,rs9984765,rs2839356,rs1051169 and rs2186358 polymorphisms in Guangxi population.And their polymorphisms has regional differences.Objective:(1)To investigate the association between S100 B gene rs9722,rs881827,rs9984765,rs2839356,rs1051169 and rs2186358 polymorphisms and susceptibility to ischemic stroke.(2)To further analyze the correlation between S100 B gene polymorphisms and the expression level of S100 B.Methods:(1)The study subjects included 396 patients with IS and 398 controls.We used SNaPshot SNP and DNA sequencing to detected the genotypes of S100 B gene rs9722,rs881827,rs9984765,rs2839356,rs1051169 and rs2186358.(2)The expression levels of serum S100 B were detected by enzyme-linked immunosorbent assay(ELISA).Results:(1)Allele analysis showed that relative to C allele,rs9722 allele T might increase the risk of IS(T vs.C: OR=1.37,95% CI,1.11~1.69,P=0.003).(2)Genotype analysis showed that individuals carrying rs9722 TT genotype had a significantly higher risk of IS than those carrying C genotype(TT vs.CC: OR=2.19,95% CI,1.30~3.68,P=0.03).After adjusting for the confounding factors,there was still statistical significance.(3)The analysis of genetic model shows that dominant model(CT+TT vs.CC)and recessive model(TT vs.CC+CT)had significant increased the risk of IS(CT+TT vs.CC: OR=1.40,95% CI,1.06~1.86,P=0.02;TT vs.CC+CT: OR=1.93,95% CI,1.17~3.18,P=0.01),and there was still statistical significance after correcting the related confounding factors.(4)Haplotype analysis showed that the haplotypes CTTTGA and CTTCC may reducethe risk of IS(CTTTGA: OR=0.54,95% CI,0.43~0.69,P<0.001;CCTTCC: OR=0.44,95% CI,0.24~0.79,P=0.005),and the haplotypes CCTTGA and TTCCCA may increase the risk of IS(CCTTGA: OR=1.69,95% CI,1.32~2.14,P<0.001;TTCCCA: OR=6.10,95% CI,3.23~11.52,P<0.001).(5)Stratification analysis showed that rs9722 polymorphism may not correlate with clinical manifestations and lipid levels of IS patients.(6)The expression level of S100 B in serum of IS patients was significantly higher than that of controls.Further analysis showed that the expression of S100 B in serum of rs9722 T allele carriers in IS group was significantly higher than that of C allele carriers.Conclusion:(1)S100B gene rs9722 T allele,TT genotype,dominant and recessive model and haplotypes of CCTTGA and TTCCCA may increase the risk of IS.(2)S100B gene rs9722 polymorphism may not correlate with clinical manifestations and serum lipid levels of IS patients.(3)S100B gene rs9722 polymorphism is related to the pathogenesis of IS.The rs9722 T allele may participate in the pathogenesis of IS by influencing the expression of serum S100 B.