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
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
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DOI：
10.1097/00008571-199608000-00003
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发表时间：
1996-08-01
期刊：
影响因子：
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通讯作者：
Cull, JG
中科院分区：
文献类型：
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作者：
Blum, K;Braverman, ER;Cull, JG
为了研究多巴胺受体基因（DRD（2））的Tag I A（1）等位基因在伴有或不伴有物质使用障碍的肥胖患者中的患病率，对来自新泽西普林斯顿的神经精神科门诊的40名患者进行了Tag I DRD（2）A（1）等位基因存在或不存在的基因分型。40名肥胖受试者的主要入选标准是体重指数（BMI）等于或大于25（未表征）; 11名肥胖受试者患有重度物质使用障碍; 20名对照者的BMI低于25; 33名物质使用障碍（不太严重）患者的BMI低于25。将数据与分为三个独立组的三组不同对照组进行统计学比较（第I组，n=20; R组，n=286;第III组，n=714）。他们根据筛选标准（药物、酒精、尼古丁滥用/依赖、BMI低于25和其他相关行为，包括父母酗酒或药物滥用史和DSM IV、轴I和轴II诊断）而不同。第II组和第III组为来自文献的群体对照。在40名白人肥胖女性和男性中测定了Tag IA（1）D（2）多巴胺受体（DRD（2））等位基因的患病率。在这个平均BMI为32.35+/-1.02的样本中，52.5%的肥胖受试者存在DRD（2）基因的A1等位基因。此外，我们发现，在23名患有物质使用障碍共病的肥胖受试者中，与17名没有物质使用障碍共病的肥胖受试者相比，DRD（2）A（1）等位基因的患病率显著增加。DRD（2）A（1）等位基因在有物质使用障碍共病的肥胖受试者中的出现率为73.9%，而在无物质使用障碍共病的肥胖受试者中的出现率为23.5%。此外，当我们评估物质使用的严重程度（酗酒，可卡因依赖等）时，药物使用严重程度的增加增加了Tag I DRD（2）A（1）等位基因的患病率;其中66.67%（8/12）的不太严重的先证者拥有A（1）等位基因，而82%（9/11）的最严重病例拥有A（1）等位基因。线性趋势分析表明，药物使用的增加与A（1）等位基因分类呈正相关（p < 0.00001）。这些初步数据表明，DRD（2）A（1）等位基因的存在不仅证实了肥胖的风险增加，而且证实了其他相关成瘾行为（以前称为奖励缺乏综合征）的风险增加，并且BMI超过25本身（没有宏观选择或共病物质使用障碍的特征）并不是与DRD（2）A（1）等位基因相关的充分标准
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 neuropsychiatric clinic in Princeton, New Jersey, were genotyped for presence 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 use disorder; 20 controls had a BMI below 25; and, 33 substance use disorder (less severe) patients had a BMI below 25. The data were statistically compared with three different sets of controls divided into three 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 Axis II diagnoses). Groups II and III were population controls derived from the literature. The prevalence of the Tag I A(1)D(2) dopamine receptor (DRD(2)) alleles was determined in 40 Caucasian obese females and 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. Furthermore, we found that in the 23 obese subjects possessing comorbid substance use disorder, the prevalence of the DRD(2) A(1) allele significantly increased compared to the 17 obese subjects without comorbid substance use disorder. The DRD(2) A(1) allele was present in 73.9% of the 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 dependence, etc.) increasing severity of drug use increased the prevalence 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 drugs was positively and significantly associated with A(1) allelic classification (p < 0.00001). These preliminary data suggest that the presence of the DRD(2) A(1) allele confirms increased risk not only for obesity, but also for other related addictive behaviours (previously referred to as the Reward Deficiency Syndrome) and that a BMI over 25 by itself (without characterization of macroselection or comorbid substance use disorders) is not a sufficient criterion for association with the DRD(2) A(1) allele