D2 receptors binding potential is not affected by Taq1 polymorphism at the D2 receptor gene.
Alcoholism and substance abuse have been associated with a polymorphism in a noncoding region of the D2 receptor gene (the A1 allele of the Taq1 'A' system) in several, but not all studies. In addition, the presence of the A1 allele has been associated with lower density of D2 receptors in the caudate nucleus in one postmortem study. If the Taq1 'A1' allele is in linkage disequilibrium with a mutation that decreases the expression of the D2 receptor gene, it is conceivable that subjects with the A1 allele might be predisposed to behaviors which stimulate dopamine transmission, such as alcoholism or substance abuse. In this study, we attempted to confirm the association between the A1 allele and lower D2 receptor density, and explored a possible association between the B1 allele and D2 receptor expression. Genotypes at the Taq1 'A' and 'B' systems were determined in 70 subjects who underwent in vivo measurement of D2 receptors-binding potential with single photon emission computerized tomography (SPECT) and the selective dopamine D2 receptor radiotracer [123I]IBZM. [123I]IBZM-binding potential was identical in A1 carriers (i.e., subjects heterozygous or homozygous for that allele) (230 +/- 85 ml g-1, n = 27) and A1 noncarriers (231 +/- 70 ml g-1, n = 43). Similarly, we found no effect of the B1 allele on [123I]IBZM-binding potential. In conclusion, the results of this study failed to replicate the previously reported association between A1 allele and lower D2 receptor expression.
Laruelle
M
M
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. laurelle@neuron.cpmc.columbia.edu
Gelernter
J
J
Innis
R B
RB
D001667:Binding, Competitive / Q000502:physiology; D001923:Brain Chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D019914:Taq Polymerase; D015899:Tomography, Emission-Computed, Single-Photon
D007457:Iodine Radioisotopes; D017448:Receptors, Dopamine D2; D019914:Taq Polymerase