MEK基因多态性与抑郁症的关联性研究

Association between MEK gene polymorphisms and depression

目的研究抑郁症患者丝裂原活化蛋白激酶/细胞外信号调节激酶激酶(MEK)基因的单核苷酸多态性(SNP),探讨MEK基因与抑郁症发病的关联性。方法采集抑郁症患者(n=425)和健康对照者(n=404)的外周静脉血,提取基因组DNA,采用Taq-Man探针SNP基因分型技术,检测两组受试者MEK1基因(rs1549854和rs4255740位点)和MEK2基因(rs7258366和rs12459484位点)4个SNP位点的基因型,并分析基因多态性与抑郁症的关系。结果①抑郁症组和对照组在rs1549854位点的基因型和等位基因频率比较,差异有统计学意义(P<0.05);两组女性受试者比较差异仍有统计学意义(P<0.01)。②对MEK1和MEK2基因的2个位点分别进行基因型联合分析和疾病风险度分析,发现抑郁症组中rs1549854 AA-rs4255740 CC和rs7258366 AA-rs12459484 GG的联合基因型分布频率均显著高于对照组,且后者危险度最高(OR=2.175,P<0.01);而抑郁症组中rs1549854 CC-rs4255740 CT和rs7258366 GG-rs12459484 GG联合基因型分布频率均显著低于对照组,且后者危险度最低(OR=0.132,P<0.01)。结论①MEK1基因的rs1549854位点可能参与了抑郁症尤其是女性抑郁症的发病。②MEK1/2基因的rs1549854 AA-rs4255740 CC和rs7258366 AA-rs12459484 GG联合基因型可能是抑郁症发病的危险因子,而rs1549854 CC-rs4255740 CT和rs7258366 GG-rs12459484GG联合基因型可能是抑郁症的保护因子。

Objective To investigate the association between mitogen-activated protein kinase/extracellular signal-regulated kinase kinase（MEK） gene polymorphisms and depression.MethodsPeripheral whole blood samples of 425 patients with major depressive disorder（depression group） and 404 healthy controls（control group） were collected,and DNA was extracted.Tagging SNPs rs1549854 and rs4255740 in MEK1 gene,rs7258366 and rs12459484 in MEK2 gene were selected and genotyped through TaqMan SNP genotyping assay to detect the genotypes of 4 SNPs in depression group and control group,and the association between MEK gene polymorphisms and depression was analysed.ResultsThere were significant differences in genotype and allelic distribution of rs1549854 between depression group and control group（P0.05）.There also existed significant differences between females of two groups（P0.01）.The combinative genotype analysis of rs1549854 and rs4255740 and that of rs7258366 and rs12459484 revealed that the combinative genotype distribution of rs1549854 AA-rs4255740 CC and rs7258366 AA-rs12459484 GG was significantly higher in depression group than that in control group,with the highest risk of the latter（OR=2.175,P0.01）,while the combinative genotype distribution of rs1549854 CC-rs4255740 CT and rs7258366 GG-rs12459484 GG was significantly lower in depression group than that in control group,with the lowest risk of the latter（OR=0.132,P0.01）.ConclusionPolymorphism of rs1549854 in MEK1 gene may relate to major depressive disorder,especially for female patients.The combinative genotype of rs1549854 AA-rs4255740 CC and rs7258366 AA-rs12459484 GG may be risk factors for depression,while that of rs1549854 CC-rs4255740 CT and rs7258366 GG-rs12459484 GG may be associated with lower risk for major depressive disorder.