NO EVIDENCE OF ASSOCIATION BETWEEN DOPAMINE D4 RECEPTOR VARIANTS AND BIPOLAR AFFECTIVE-DISORDER

Disturbance in the dopamine neurotransmitter system has been implicate d in the pathogenesis of affective disorder. In this study, we examine the possibility that functional variants of the recently cloned dopam ine D4 receptor gene contribute to the genetic component of manic depr ession. The polymorphism, a 48 bp tandem repeat coding for part of the third cytoplasmic loop, was detected using a PCR based method. In a f irst sample of 57 patients and 59 controls, we found allele 7 to be in excess in the patients. In contrast, allele 3 was less frequent in pa tients. A second, larger sample of 90 patients and 91 controls was uti lized to test these hypotheses. Data from the two samples were then po oled together for further analyses. We calculated the power of our sam ples, and if the frequency of 7 repeat allele obtained from sample 1 i s true, i.e., 25% (28/114) for patients and 14% (16/118) for controls, then the power of the combined sample is 62% at 5% (two-tailed) signi ficance level. However, both observations were not replicated; we ther efore conclude that variations in this repeat at the DRD4 gene do not contribute to the genetic component of manic depression. (C) 1994 Wile y-Liss, Inc.