Synaptogyrin 1 gene (SYNGR1) is considered as a positional candidate gene for
schizophrenia because of its location at chromosome 22q13, a region linked to
schizophrenia, and its reduced expression in postmortem brain of patients with
schizophrenia. Additionally, genetic studies also reported association of SYNGR1 is with
schizophrenia and
bipolar disorder in southern India. Prompted by these findings, we were interested to know if SYNGR1 is also associated with
schizophrenia in our population. Therefore, we systematically searched for SYNGR1 mutations in a cohort of Han Chinese patients from Taiwan. Four single nucleotide polymorphisms (SNPs) were identified, including three at the putative core promoter region (g.-673A>C, g.-377G>A and g.-318G>T) that are in strong linkage disequilibrium and one in intron 2 (IVS2-64C>G). Computer program predicts that g.-637A>C and g.318G>T may change transcription binding sites of
AP-1 and TGT3, respectively. We further carried out SNP- and haplotype-based case-control association studies of these tress SNPs with
schizophrenia. However, no association was detected between these SNPs and
schizophrenia in our sample. Nevertheless, we identified several rare mutations in exon 6 of SYNGR1 gene in our patient cohort (n=497), including a 3-bp (AAC) in-frame insertion between
codon 202 and 203 (P202_T203insN) in two patients, an A-to-G missense mutation (c.665A>G) at
codon 222 (D222G) in one patient, a synonymous mutation (c.669C>T) at
codon 223 (T223T) in one patient, and a C-to-T at
3' UTR of SYNGR1 (c.772C>T) in one patient. These are mutations were not found in 507 control subjects, suggesting further functional assays are warranted to verify their relevance to the pathogenesis of
schizophrenia.