Association of SLC6A4 and HTR2A gene polymorhisms in schizophrenia

Abstract

Schizophrenia (Sz) affect about 21 million people worldwide. This disorder alters perception, thoughts, affect and behaviour. Serotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter which has been hypothesized to be abnormal in schizophrenia. The solute carrier family 6 member 4 (SLC6A4) gene and serotonin receptor 2A (HTR2A) gene are among the important genes within the serotonergic system-related genes family. The SLC6A4 gene encode for serotonin transporter (SERT) which regulates the synaptic concentration of serotonin by transporting serotonin molecules back to the pre-synaptic neuron while the HTR2A gene is another gene that encode for the serotonin receptor subtype 2A. Studies done previously failed to produce consistent result for specific locus of schizohrenia susceptibility. Moreover, multiracial group in Malaysia may have different gene susceptibility to this disorder. The current study investigated the association of SNPs within SLC6A4 and HTR2A gene as genetic susceptibility marker of schizophrenia. Other than that, allele and genotype of these genes were further stratified based on psycho-pathological symptoms. A total of 240 Sz patients and 364 normal controls were studied. Genomic DNA was extracted from peripheral blood. Rs12449783, rs140700, rs6352 and rs6354 of SLC6A4 gene were selected and genotyped using allelic discrimination real time Taqman® assay while rs6311, rs7325200 and rs7324942 of HTR2A gene were genotyped using PCR-RFLP method. A significant association was found between rs12449783 of SLC6A4 gene and schizophrenia for both alleles and genotypic frequencies (p = 1.68 x 10−8 and 5.11 x 10−7 respectively) regardless of the races and gender. None of the SNPs show significant relationship with all dimension of psycho-pathological symptoms of schizophrenia. There were also no significant association between the 3 HTR2A SNPs with schizophrenia and the five factor analysis of PANSS. In conclusion, the significant association between SLC6A4 gene in our schizophrenia samples reaffirmed the previous similar findings among Chinese Han in Beijing thus support role of SLCA4 gene in schizophrenia.