The Association Study Of SIAT8B And PDLIM5 In The Chinese Han Population

Schizophrenia is a common and complex mental disorder that is clinically characterized by delusions, conceptual disorganization, hallucinatory behavior, cognitive dysfunction, blunted affect and psychosocial impairment. The world-wide prevalence of the disorder is approximately 1%, regardless of race, gender and economic conditions. Although the aetiology of schizophrenia still remains unknown, twin, family, and adoption studies have provided consistent evidence that genetic factors play an important role in its pathogenesis.The Sialyltransferase 8B gene (SIAT8B) is located at 15q26, a susceptibility region for both schizophrenia and bipolar disorder. The protein encoded by this gene has an important role in neural development and sialic acid synthesis on the neural cell adhesion molecule (NCAM). A previous research has indicated that the promoter region of SIAT8B is associated with schizophrenia in the Japanese population. To take this further we carried out an association study based on 643 unrelated schizophrenics and 527 unrelated healthy subjects, who are Han Chinese in origin, recruited from Shanghai. Although our results differed from those of the Japanese research, rs3759915, which is also located in the promoter region of SIAT8B, showed nominally significant association with schizophrenia (P=0.0036). Moreover, haplotypes constructed from rs3759915 and another two SNPs reported in the Japanese study (rs3759914 and rs3759916, located in the promoter region of SIAT8B), which located in the same LD block, were significantly associated with schizophrenia (global P=0.0000050). Our findings indicate that SIAT8B may be a candidate susceptibility gene for schizophrenia in the Chinese Han population and may also provide further support for the potential importance of polysaccharide-synthesizing genes in the etiology of schizophrenia.The PDZ and LIM domain 5 protein (PDLIM5), which is known as enigma-homologue LIM domain (ENH) protein or LIM protein, contains one PDZ (postsynaptic density-95/discs large/zone occludens-1) domain and three LIM (Lin-11, Isl-1, and Mec-3) domains. DNA microarray analysis of postmortem brains of schizophrenics has indicated up-regulation of the mRNA level of PDLIM5, and Horiuchi et al. reported two SNPs (rs2433320 and rs2433322) in the 5' region of PDLIM5 to be significantly associated with schizophrenia in the Japanese population. On the other hand, no association with schizophrenia was observed by Kato et al. in a different sample of the Japanese population. In this study, we genotyped six SNPs (including rs2433320 and rs2433322) covering PDLIM5 in 507 schizophrenia patients and 530 normal controls recruited from Jiangxi Province, China. Though rs2433320 was negative in our samples, rs2433322 showed significantly different frequencies between cases and controls (P=0.000010). In addition, high LD was observed between rs2433320 and rs2433322 (D'=0.880), and haplotypes constructed from the two SNPs were significantly associated with schizophrenia (Global P=0.00019 even after strict Bonferroni correction). Our results provide further evidence to support PDLIM5 as a potential susceptible gene for schizophrenia.