Association between the Dopamine D2 Receptor A2/A2 Genotype and Smoking Behavior in the Japanese

Association between the Dopamine D2 Receptor A2/A2 Genotype and Smoking Behavior in the Japanese1

Departments of Pulmonary Medicine [K. Y., K. M., T. S.] and Pathology and Clinical Laboratories [K. O.], Aichi Cancer Center Hospital; and Divisions of Epidemiology [N. H.] and Molecular Oncology [K. K., H. S., T. T.], Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464-8681, Japan

Abstract

For the study presented here, we investigated possible links between the dopamine D2 receptor (DRD2) TaqIA genotype (DRD2*A) and smoking behavior in a total of 332 Japanese individuals. For the first time, functional insertion/deletion polymorphism (−141C Ins/Del) in the DRD2 promoter was also examined in relation to smoking behavior. The distribution of the DRD2*A genotype was significantly different among current, former, and never-smokers (P = 0.001; χ² test), and smoking appeared to be associated with the DRD2 A2/A2 genotype, showing marked contrast to previous reports for non-Hispanic whites in the United States. Multivariate logistic regression analysis incorporating age, sex, genotype, and smoking status as variables revealed that DRD2 A2/A2 genotype was significantly associated with an increased risk of predisposition to smoking behavior in the Japanese (odds ratio, 3.680; 95% confidence interval, 1.499–9.052). In contrast, such an increased risk was not observed in terms of association with the −141C Ins/Del polymorphism. These findings suggest an association of the DRD2*A genotype with an increased risk of being predisposed to smoking behavior in the Japanese and suggest the possible existence of ethnic group-specific differences, which warrant additional studies on the underlying molecular mechanism.

Footnotes

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↵1 Supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture, Japan, and by a Grant from the Smoking Research Foundation.
↵2 These two authors contributed equally to this study.
↵3 To whom requests for reprints should be addressed, at Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-Ku, Nagoya 464-8681, Japan. Phone: 81 (52) 764-2983; Fax: 81 (52) 764-2993; E-mail: tak{at}aichi-cc.pref.aichi.jp
↵4 The abbreviations used are: DRD2, dopamine D2 receptor; −141C Ins/Del, an insertion/deletion polymorphism at −141C of DRD2.
- Accepted February 11, 1901.
- Received June 14, 1900.
- Revision received January 3, 1901.