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

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