Identification of three polymorphisms in the translated region of PLC-gamma 1 and their investigation in lithium responsive bipolar disorder

Recently, we have found an association between bipolar disorder patients wh o are excellent responders to lithium prophylaxis and a polymorphic marker located in the first intron of the phospholipase C-gamma1 gene (PLC-gamma1) [Turecki et al,, 1998: Mol Psychiatry 3:534-538]. As this variant is not k nown to be functional, we searched for other markers within the coding reg- ion, using single-strand conformational polymorphism (SSCP) analysis. We ha ve identified three polymorphic sites localized in three different exons of the PLC-gamma1 gene (exons 9, 26, 31). Variation studies of these potentia lly functional sites in a group of 133 bipolar patients with an excellent r esponse to lithium prophylaxis and a comparison group of 99 healthy control s showed no difference in genotype distributions for exon 9 (chi-square = 1 .41, df = 2, P = 0.49), exon 26 (chi-square = 2.26, df = 2, P = 0.13), or e xon 31 (chi-square = 1.41, df = 2, P = 0.49). Similar results were observed for allele distributions. These results suggest that our previous findings were not the result of linkage disequilibrium with these variants. (C) 200 1 Wiley-Liss, Inc.