5-HT1A receptor (HTR1A) 5′ region haplotypes significantly affect protein expression in vitro

The aim of this study was to explore the role of two SNPs (rs6295 & rs113195492) in the HTR1A gene promoter region that regulates the expression of the 5-HT1A receptor. A fragment spanning from −551 to +672 of HTR1A (Transcription start site +1) was cloned into the pGL-3 Basic Vector and three haplotype plasmids composed of two SNPs were constructed. HEK-293 cells and the SK-N-SH cells were transfected with the three plasmids, and the relative fluorescence intensity was measured. In HEK-293 cells, there was a significant difference when the relative fluorescence intensity of plasmid 1-1 was compared to that of plasmid 2-1. However, no significant difference was observed when the luciferase expression of plasmid 2-1 and plasmid 3-1 was analyzed. We also found that the expression trend of the SK-N-SH cells was similar to the HEK-293 cells, but the overall relative fluorescence intensity of the SK-N-SH cells was lower than that of the HEK-293 cells. Our finding showed that the rs6295 SNP, as a suspected variant that indicates susceptibility to schizophrenia, exhibited a higher transcriptional activity. The influence of the rs113195492 locus on schizophrenia needs to be explored further.