DRD2 allele frequencies and linkage disequilibria, including the -141CIns/Del promoter polymorphism, in European-American, African-American, and Japanese subjects.
Although many studies have addressed the possible association of D2 dopamine receptor (DRD2) alleles-particularly in the TaqI "A" system (with the DRD2*A1 allele)-with positive results for a range of behavioral phenotypes in populations of European origin, the interpretation of those results remains controversial; they could reflect physiological relationships between gene and phenotype, population stratification, or random variation. Since mutational analysis studies of the DRD2 gene have thus far failed to reveal a mutation that could provide a physiological basis for these results, functional meaning for them depends on linkage disequilibrium with a functional variant. A recently described functional variant in the DRD2 promoter (-141CIns/Del), which is about 250 kb 5' to the variants studied in psychiatric illness, could conceivably provide an explanation for the positive findings, if it were in linkage disequilibrium with DRD2*A1 in populations similar to those for which an association has been reported. We studied linkage disequilibrium (LD) and frequencies of haplotypes containing the DRD2*A, DRD2*D, and -141CIns/Del systems in European-Americans, African-Americans, and Japanese subjects. Although we found evidence for LD across the 250-kb first intron in both American populations, we did not find significant LD between the DRD2*A system and the -141CIns/Del system in the European-Americans. This newly described functional variant therefore does not provide a straightforward physiological explanation for previously reported genetic associations with DRD2*A1 in European-American subjects.
Gelernter
J
J
Division of Molecular Psychiatry, Yale University School of Medicine, West Haven, Connecticut, 06516, USA. gelernter-joe@cs.yale.edu
Kranzler
H
H
Cubells
J F
JF
Ichinose
H
H
Nagatsu
T
T
D000483:Alleles; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D003237:Connecticut; D005060:Europe / Q000208:ethnology; D005787:Gene Frequency; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D001523:Mental Disorders / Q000209:etiology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D044469:Racial Groups / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D044465:White People / Q000235:genetics; D001741:Black or African American
D017448:Receptors, Dopamine D2