Abstract:

Objective To investigate the association between mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) gene polymorphisms and depression. Methods Peripheral 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. Results There were significant differences in genotype and allelic distribution of rs1549854 between depression group and control group (P<0.05). There also existed significant differences between females of two groups (P<0.01). 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, P<0.01), 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, P<0.01). Conclusion Polymorphism 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.

Key words: depression, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, single nucleotide polymorphism