rs4379368基因突变在畲族人偏头痛中的价值及相关机制初探

The Value of rs4379368 Gene Mutation in Migraine of She Nationality and Its Related Mechanisms

目的初步探讨rs4379368基因突变对畲族偏头痛病人的影响,并分析其诊断价值。方法选取300例畲族偏头痛病人作为病例组,另选取300名畲族正常人群作为对照组。收集两组外周血,并采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术检测rs4379368基因突变情况;采用酶联免疫吸附试验(ELISA)检测各组血清脑源性神经营养因子(BDNF)、酪氨酸激酶受体B(TrkB)、磷酸化细胞外调节蛋白激酶(p-ERK)和磷酸化环磷酸腺苷(cAMP)反应结合蛋白(p-CREB)水平。结果rs4379368位点聚合酶链式反应(PCR)扩增片段长度为258 bp,经HphI内切酶酶切琼脂糖凝胶电泳分离后有2个等位基因(C和T)和3种基因型(CC型、CT型和TT型)。应用拟合优度χ2检验分析病例组和对照组基因型分布符合Hardy-Weinberg平衡规则;但两组等位基因和基因型频数分布比较,差异均有统计学意义(P<0.05)。与对照组比较,病例组血清BDNF、TrkB、p-ERK和p-CREB蛋白水平明显升高,差异均有统计学意义(P<0.05)。Spearman相关分析结果显示,基因型TT与血清BDNF、TrkB、p-ERK和p-CREB呈正相关(P<0.05),基因型CC则与血清BDNF、TrkB、p-ERK和p-CREB呈负相关(P<0.05),基因型CT与血清BDNF、TrkB、p-ERK和p-CREB无相关性(P>0.05)。结论rs4379368位点等位基因及基因型在畲族偏头痛病人和畲族正常人群中差异明显,有一定鉴别诊断价值,其中基因型CC和基因型TT与血清BDNF、TrkB、p-ERK和p-CREB水平密切相关。

Objective To investigate the effect of rs4379368 gene mutation on migraine patients in She nationality(patient group)and to analyze its diagnostic value.Methods Three hundred migraine patients of She nationality and 300 normal population of She nationality were selected as patient group and control group respectively.The peripheral blood of two groups was collected,and the mutation of rs4379368 gene was detected by restriction fragment length polymorphism polymerase chain reaction(PCR-RFLP).The serum levels of brain derived neurotrophic factor(BDNF),tyrosine kinase receptors B(TrkB),phosphorylated extracellular-regulated kinases(p-ERK),and phosphorylated cAMP-responsive element-binding(p-CREB)protein were detected by enzyme-linked immunosorbent assay(ELISA).Results The length of PCR amplified fragment of rs4379368 locus was 258 bp,and 2 alleles C and T were isolated after HphI endonuclease digestion and agarose gel electrophoresis.Three genotypes were CC,CT,and TT.The results of goodness-of-fit test showed that the distribution of genotypes in patient group and control group accorded with Hardy-Weinberg equilibrium rule,but there were significant differences in allele and genotype frequency distribution between two groups(P<0.05).Compared with control group,the serum levels of BDNF,TrkB,p-ERK,and p-CREB in patient group were significantly higher,and the difference was statistically significant(P<0.05).The Spearman correlation analysis showed that genotype TT was positively correlated with serum BDNF,TrkB,p-ERK,and p-CREB(P<0.05),while genotype CC was negatively correlated with serum BDNF,TrkB,p-ERK,and p-CREB(P<0.05),while genotype CT was not significantly correlated with serum BDNF,TrkB,p-ERK,and p-CREB(P>0.05).Conclusion The alleles and genotypes of rs4379368 locus are significantly different between She migraine patients and She normal population,with certain value in differential diagnosis.Genotype CC and TT are closely related to serum levels of BDNF,TrkB,p-ERK,and p-CREB.