Allelic variation of a BalI polymorphism in the DRD3 gene does not influence susceptibility to bipolar disorder: Results of analysis and meta-analysis

Bipolar disorder is a major psychiatric illness that has evidence for a sig nificant genetic contribution toward its development. In recent years, the Hall RFLP (restriction fragment length polymorphism) in the dopamine D3 rec eptor gene has been examined as a possible susceptibility factor for both s chizophrenia and bipolar disorder. While analysis in schizophrenia has prod uced examples of increased homozygosity in patients, less encouraging resul ts have been found for bipolar disorder. Recently, however, a family-based association study has found a significant excess of allele 1 and allele 1-c ontaining genotypes in transmitted alleles to bipolar probands over nontran smitted controls. In a large bipolar case control sample (n = 454), we have been unable to replicate the family-based association study (chi-square = 0.137, P = 0.71, 1 df) or detect an effect similar to the positive homozygo sity findings in schizophrenia (chi-square = 0.463, P = 0.50, 1 df). A meta analysis of previous association studies also revealed no difference in all ele distributions between bipolar patients and controls for this polymorphi sm in ethnically homogeneous samples (odds ratio, OR,= 1.04; P = 0.60; 95% confidence interval, CI, = 0.89-1.20). In view of this evidence, we conclud e that variation at the Ball RFLP is not an important: factor influencing t he susceptibility to bipolar disorder. It remains possible, however, that o ther sequence variations within the DRD3 gene could play a role. (C) 2001 W iley-Liss, Inc.