Association and functional study of and gene polymorphisms with depression in Chinese population.

BACKGROUND

Depression is a disease with a significant global social burden. Single nucleotide polymorphisms (SNPs) are correlated with the development of depression. This study investigates the relationship between polymorphisms in the and gene promoter regions and susceptibility to depression in the Chinese population.

AIM

To provide new insights into identifying SNPs for predicting depression in the Chinese population.

METHODS

We conducted a case-control study involving 555 individuals with depression and 509 healthy controls. rs8020095 and rs3759755, rs10144417, rs2031564, and rs8016024 in the promoter region were genotyped using next-generation sequencing. Dual luciferase reporter genes were employed to assess the transcriptional activity of promoter regions for each SNP genotype, with transcription factors binding to each site predicted using the JASPAR database.

RESULTS

Compared to healthy controls, the promoter rs10144417 AG genotype ( = 0.015), rs3759755 AC/CC genotype ( = 0.036), and gene rs8020095 GA and AA genotypes (GA: = 0.028, GG: = 0.025) were significantly associated with a lower prevalence of depression. Linked disequilibria were present in five SNPs, with the AGATA haplotype frequency in patients significantly lower than in healthy subjects ( = 0.023). Luciferase activity of the rs3759755-A recombinant plasmid was significantly higher than that of the rs3759755-C recombinant plasmid ( = 0.026), and the rs8020095-A recombinant plasmid activity was significantly higher than that of the rs8020095-G recombinant plasmid ( = 0.001). Transcription factors orthodenticle homeobox 2, orthodenticle homeobox 1, forkhead box L1, NK homeobox 3-1, and nuclear factor, interleukin 3 regulated demonstrated binding affinity with rs3759755A > C and rs8020095A > G.

CONCLUSION

This study demonstrates that SNPs (rs3759755 and rs10144417) in the promoter region of the and SNP (rs8020095) of are indeed associated with susceptibility to depression.