FYN kinase gene: another glutamatergic gene associated with bipolar disorder?

Several genes of the glutamatergic system have been implicated in both schizophrenia and bipolar disorder. The Src family tyrosine kinase FYN plays a key role in the interaction between brain-derived neurotrophic factor and glutamatergic receptor N-methyl-D-aspartate. Although no association between FYN gene polymorphisms and schizophrenia has been demonstrated, in our previous paper we found an association between FYN polymorphisms and cognitive test performance in schizophrenic patients. The aim of this study was to find a possible association of three polymorphisms of the FYN gene with bipolar disorder. We analyzed 425 bipolar patients and 518 control subjects. Genotypes of three analyzed polymorphisms, i.e. rs706895 (-93A/G in the 5'-flanking region), rs6916861 (Ex12+894T/G in the 3'-UTR) and rs3730353 (IVS10+37T/C in intron 10) were established by PCR-RFLP. A significant association was found between rs6916861 T/G and rs3730353 T/C polymorphisms of the FYN gene and bipolar disorder. These results were also significant in the subgroups of bipolar I and early-onset (<18 years) bipolar disorder patients. No association with -93 A/G polymorphism was found. Haplotype analysis revealed that rs6916861 T/G and rs3730353 T/C polymorphisms are in linkage disequilibrium (r(2) = 0.86, D' = 0.93 with 95% CI = 0.9-0.97). The results suggest that the glutamatergic FYN gene may be associated with bipolar disorder, particularly with type I illness and early age of onset.