Study of association between schizophrenia and functional polymorphisms of genes encoding Bcl-2 family proteins

It is proposed that both preand postnatal as well as genetically determined abnormalities of the apoptotic processes are among factors responsible for the development of schizophrenia. The ultimate vulnerability of cells to diverse apoptotic stimuli is determined by the relative ratio of various pro-apoptotic and anti-apoptotic members of the B-cell lymphoma 2 (Bcl-2) family proteins among which Bcl-2 proper is a major anti-apoptotic protein, and Bcl-2-associated X protein (Bax) is pro-apoptotic death promoter. Postmortem studies demonstrated the increased expression level of Bax encoding gene and high Bax/Bcl-2 proteins ratio in schizophrenia. However, it is yet unclear whether these alterations are genetically determined or caused by other factors. In the present study we, for the first, time evaluated the association of single nucleotide polymorphisms (SNPs) rs1057369 (A>G) and rs956572 (G>A), rs1801018 (A>G) of Bax and Bcl-2 encoding genes, BAX and BCL2, respectively, with schizophrenia in Armenian population using polymerase chain reaction with sequence-specific primers. BAX rs1057369 SNP was found negatively associated with this disorder; the presence of BAX rs1057369*G minor allele, especially in homozygous form, was associated with decreased risk of developing schizophrenia, whereas no association between schizophrenia and BCL2 rs956572 and rs1801018 polymorphisms was revealed. Based on the obtained results we concluded that the rs1057369*G minor allele of BAX may have a protective effect relative to schizophrenia, and that this effect is most pronounced in individuals with GG homozygous genotype.