DRD2 allele frequencies and linkage disequilibria, including the -141CIns/Del promoter polymorphism, in European-American, African-American, and Japanese subjects

• Published in: Genomics (San Diego, Calif.) Calif.), 1998-07, Vol.51 (1), p.21
• Main Authors: Gelernter, J, Kranzler, H, Cubells, J F, Ichinose, H, Nagatsu, T
• Format: Article
• Language: English
• Subjects: Alleles; Asian People - genetics; Black or African American; Black People - genetics; Connecticut; Europe - ethnology; Gene Frequency; Humans; Japan; Linkage Disequilibrium; Mental Disorders - etiology; Polymorphism, Genetic; Promoter Regions, Genetic; Racial Groups - genetics; Receptors, Dopamine D2 - genetics; White People - genetics
• ISSN: 0888-7543
• DOI: 10.1006/geno.1998.5264

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.