CASE-CONTROL, HAPLOTYPE RELATIVE RISK AND TRANSMISSION DISEQUILIBRIUMANALYSIS OF A DOPAMINE D2 RECEPTOR FUNCTIONAL PROMOTER POLYMORPHISM IN SCHIZOPHRENIA

The dopamine system has long been suspected of aetiological involvemen t in schizophrenia because of a number of lines of evidence pointing t o excess dopaminergic activity in the illness. Recently, negative alle lic association was reported between a single base deletion in the pro moter region of the DRD2 gene, - 141 Delta C, and schizophrenia, with an odds ratio of 0.60, This was of particular interest since the delet ion, which occurs in about 22% of the Japanese population, is function al in that it results in reduced (20-40% of wild-type) basal levels of receptor expression. We have examined this polymorphism in 229 family trios from SW China, consisting of both parents and a single offsprin g affected by schizophrenia, and 151 Caucasian cases with schizophreni a and 145 Caucasian normal controls from the UK. Using the haplotype-b ased haplotype relative risk method (HHRR), the frequency of the -141 Delta C allele was 6.9% in the affected Chinese subjects compared to a n estimated frequency of 9.0% in this population (chi(2)=1.21, 1 df, n s), with an odds ratio of 0.76 (95%CI 0.46-1,25). Using the transmissi on disequilibrium test, we likewise found no evidence for linkage or l inkage disequilibrium with this polymorphism (chi(2) = 0,94, 1 df, ns) . In the Caucasian cases, the frequency of the - 141 Delta C was 13% c ompared to 10% in controls (chi(2) = 1.57, p = 0.21) with an odds rati o of 1.39 (95%CI 0,81-2,40). We thus conclude that the DRD2 - 141 Delt a C polymorphism is less frequent in Chinese and Caucasian populations (9%) than in Japan (22%) and is not a significant risk factor for sch izophrenia in our populations. The - 141 Delta C allele remains a stro ng candidate for a variety of other traits and diseases, including rew ard-related behaviours such as drug abuse, which have been associated with the dopamine system. (C) 1998 Elsevier Science B.V. All rights re served.