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

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Abstract
Bipolar disorder is a major psychiatric illness that has evidence for a significant genetic contribution toward its development. In recent years, the BalI RFLP (restriction fragment length polymorphism) in the dopamine D3 receptor gene has been examined as a possible susceptibility factor for both schizophrenia and bipolar disorder. While analysis in schizophrenia has produced examples of increased homozygosity in patients, less encouraging results have been found for bipolar disorder. Recently, however, a family-based association study has found a significant excess of allele 1 and allele 1-containing genotypes in transmitted alleles to bipolar probands over nontransmitted 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 homozygosity findings in schizophrenia (chi-square = 0.463, P = 0.50, 1 df). A meta-analysis of previous association studies also revealed no difference in allele distributions between bipolar patients and controls for this polymorphism 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 conclude that variation at the BalI RFLP is not an important factor influencing the susceptibility to bipolar disorder. It remains possible, however, that other sequence variations within the DRD3 gene could play a role.