Relationship between genetic polymorphisms in the HTR1A gene and paranoid schizophrenia in a northern Han Chinese population.

The hypothesis for the etiology of schizophrenia involves various neurotransmitters, including 5-HT. Metabolic disorder of 5-HT is an important underlying neurobiochemical cause leading to the development of mental illness. Abnormality in the receptors involved in 5-HT synthesis and metabolism may affect the functioning of 5-HT in the central nervous system. There are seven types of 5-HT receptor families, with a total of 15 corresponding subtypes. HTR1A is the most abundantly expressed 5-HT receptor subtype in the mammalian brain. SNPs in HTR1A enhance or weaken the functioning of 5-HT by affecting HTR1A expression levels or ligand-binding activity, thereby placing HTR1A in an important role in the study of diseases of the nervous system. This study employed DNA sequencing to investigate HTR1A fragment lengths, including complete exons as well as 5' FR and 3' FR segments, for a total of 2,718 bp. Seven SNP loci (ss212928868, rs6295, rs6294, ss218178047, rs34118353, rs6449693, and rs878567) were found in 182 healthy volunteers and 161 patients. Among them, two SNP loci had not been reported in the National Center for Biotechnology Information (NCBI) database, promoter locus ss212928868 and exon locus ss218178047, which now have been approved by the NCBI database and assigned rs numbers, rs113195492 and rs112846276, respectively. ss212928868 and rs6294 were statistically different between control and paranoid schizophrenic women (P < 0.05), and both loci were in a state of linkage disequilibrium. However, statistical significance was lost after Bonferroni correction. Compared with the GG genotype, the GA + AA genotype had a decreased disease risk (odds ratio(GA + AA) = 0.3529, 95 % confidence interval = 0.1319-0.9444). The data showed that changes in SNP loci of HTR1A were different between paranoid schizophrenic and control group women. Although such differences were lost after statistical correction, studies with larger sample sizes have not been conducted. Combined with the newly discovered loci, these findings can point out possible directions for future investigations in different populations.