INCREASED PREVALENCE OF THE TAQ-I A(1) ALLELE OF THE DOPAMINE-RECEPTOR GENE (DRD(2)) IN OBESITY WITH COMORBID SUBSTANCE USE DISORDER - A PRELIMINARY-REPORT
K. Blum et al., INCREASED PREVALENCE OF THE TAQ-I A(1) ALLELE OF THE DOPAMINE-RECEPTOR GENE (DRD(2)) IN OBESITY WITH COMORBID SUBSTANCE USE DISORDER - A PRELIMINARY-REPORT, Pharmacogenetics, 6(4), 1996, pp. 297-305
In order to investigate the prevalence of the Tag I A(1) allele of the
dopamine receptor gene (DRD(2)) in obesity with and without comorbid
substance use disorder, a total of 40 patients, from an outpatient neu
ropsychiatric clinic in Princeton, New Jersey, were genotyped for pres
ence or absence of the Tag I DRD(2) A(1) allele. The primary inclusion
criterion for 40 obese subjects was a body mass index (BMI) equal to
or over 25 (uncharacterized); 11 obese subjects had severe substance u
se disorder; 20 controls had a BMI below 25; and, 33 substance use dis
order (less severe) patients had a BMI below 25. The data were statist
ically compared with three different sets of controls divided into thr
ee separate groups (Group I, n=20; Group R, n=286; Group III, n=714).
They differed according to screening criteria (drug, alcohol, nicotine
abuse/dependence, BMI below 25 and other related behaviours including
parental history of alcoholism or drug abuse and DSM IV, Axis I and A
xis II diagnoses). Groups II and III were population controls derived
from the literature. The prevalence of the Tag I A(1)D(2) dopamine rec
eptor (DRD(2)) alleles was determined in 40 Caucasian obese females an
d males. In this sample with a mean BMI of 32.35+/-1.02, the Al allele
of the DRD(2) gene was present in 52.5% of these obese subjects. Furt
hermore, we found that in the 23 obese subjects possessing comorbid su
bstance use disorder, the prevalence of the DRD(2) A(1) allele signifi
cantly increased compared to the 17 obese subjects without comorbid su
bstance use disorder. The DRD(2) A(1) allele was present in 73.9% of t
he obese subjects with comorbid substance use disorder compared to 23.
5% in obese subjects without comorbid substance use disorder. Moreover
, when we assessed severity of substance usage (alcoholism, cocaine de
pendence, etc.) increasing severity of drug use increased the prevalen
ce of the Tag I DRD(2) A(1) allele; where 66.67% (8/12) of less severe
probands possessed the A(1) allele compared to 82% (9/11) of the most
severe cases. Linear trend analyses showed that increasing use of dru
gs was positively and significantly associated with A(1) allelic class
ification (p < 0.00001). These preliminary data suggest that the prese
nce of the DRD(2) A(1) allele confirms increased risk not only for obe
sity, but also for other related addictive behaviours (previously refe
rred to as the Reward Deficiency Syndrome) and that a BMI over 25 by i
tself (without characterization of macroselection or comorbid substanc
e use disorders) is not a sufficient criterion for association with th
e DRD(2) A(1) allele