Polymorphisms of the sigma(1) receptor gene in schizophrenia: An association study

Possible involvement of sigma receptors in the pathogenesis of schizophreni a has been suggested. In this study we searched systematically for polymorp hisms in the 5'-flanking region of the sigma(1) receptor. Genetic variation in this region could reduce the expression! of the gene, and this suggesti on is compatible with findings of reduced sigma binding sites in several co rtical regions of schizophrenia. We confirmed G-241T and G-240T polymorphis ms; these two consecutive polymorphisms were resolved to be in complete lin kage disequilibrium with each other by single-strand conformation polymorph ism (SSCP) analysis. We also identified the A61C (Gln2Pro) polymorphism, wh ich was in almost complete linkage disequilibrium with G-241T/G-240T. There was no significant difference in the distribution of alleles or overall ge notypes of the polymorphisms between schizophrenic patients (n. = 129) and controls (n = 140). We found slight increased homozygosity for T-241/T-240 and C61 in patients compared with controls using multiple comparison (p = 0 .045). However, the significance did not remain when a Bonferroni correctio n was made (p = 0.135). These results do not support that the sigma(1) rece ptor gene plays a major role ill the pathogenesis of schizophrenia. Am. J, Med, Genet, (Neuropsychiatr, Genet.) 96:118-122, 2000. (C) 2000 Wiley-Liss, Inc.