CX3CL1 rs170364 gene polymorphism has a protective effect against major depression by enhancing its transcriptional...

Studies have shown that adult hippocampal neurogenesis may be a cause of depression. CX3CL1 is a chemokine that plays an important role in adult neurogenesis. This study aimed to investigate the relationship between CX3CL1 polymorphisms (rs170364) and the risk of depression. A case-control study of 502 patients with major depression and 504 gender-matched and age-matched healthy controls was performed. All subjects were recruited from the Chinese Han population. Next-generation sequencing was used to genotype the CX3CL1 rs170364 locus. In addition, the effect of the rs170364 polymorphism on transcription of CX3CL1 was investigated through the use of luciferase reporter constructs and in vitro analysis in SH-SY5Y cells. Our results demonstrated that the T allele and GT + TT genotype of the CX3CL1 rs170364 locus were associated with a reduced risk of major depression. Subgroup analysis found that this significant association was consistently found in females but not in males. In vitro experiments found that the rs170364 mutation enhanced the transcriptional activity of CX3CL1. These results suggest that T allele and GT + TT genotypes of the CX3CL1 rs170364 locus may be a protective factor against the onset of depression in the Chinese Han population, especially in females. SNP rs170364 enhances the transcriptional activity of CX3CL1.