The dopamine system has long been suspected of aetiological involvement in schizophrenia
because of a number of lines of evidence pointing to excess dopaminergic activity
in the illness. Recently, negative allelic association was reported between a single
base deletion in the promoter region of the DRD2 gene, -141 delta C, and schizophrenia,
with an odds ratio of 0.60. This was of particular interest since the deletion, which
occurs in about 22% of the Japanese population, is functional 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 offspring affected by schizophrenia, and 151 Caucasian cases with schizophrenia
and 145 Caucasian normal controls from the UK. Using the haplotype-based haplotype
relative risk method (HHRR), the frequency of the -141 delta C allele was 6.9% in
the affected Chinese subjects compared to an estimated frequency of 9.0% in this population
(chi 2 = 1.21, 1 df, ns), with an odds ratio of 0.76 (95% CI 0.46-1.25). Using the
transmission disequilibrium test, we likewise found no evidence for linkage or linkage
disequilibrium with this polymorphism (chi 2 = 0.94, 1 df, ns). In the Caucasian cases,
the frequency of the -141 delta C was 13% compared to 10% in controls (chi 2 = 1.57,
p = 0.21) with an odds ratio of 1.39 (95% CI 0.81-2.40). We thus conclude that the
DRD2 -141 delta C polymorphism is less frequent in Chinese and Caucasian populations
(9%) than in Japan (22%) and is not a significant risk factor for schizophrenia in
our populations. The -141 delta C allele remains a strong candidate for a variety
of other traits and diseases, including reward-related behaviours such as drug abuse,
which have been associated with the dopamine system.