A study of development of susceptibility genes related to modification of a living habit behavior for prevention of lifestyle related diseases.

本研究的目的是开发与改变生活习惯行为相关的易感基因，以预防与生活方式相关的疾病。我们将该基因命名为行为改变易感基因。我们试图开发一种预防生活方式相关疾病的方案。首先，我们调查了吸烟习惯与CYP2A6基因多态性的关联，因为尼古丁是吸烟依赖的罪魁祸首，主要由CYP2A6代谢。目前已有多种类型的细胞色素P450 2A6基因多态性的报道。在重度吸烟者中，携带CYP2A6de1等位基因的比例(22%，n=20)低于轻度吸烟者和不吸烟者(35%，n=40)。停止吸烟者的肥胖频率低于不戒烟者。β3肾上腺素能受体基因Trp64Arg突变与肥胖有关，但该突变是否与体重减轻有关尚不清楚。我们研究了携带ADRB3基因Trp64Arg突变的日本男性对体重减轻的反应。在体重指数基线上，ADRB3基因突变的参与者和无突变的参与者之间没有显著差异。体重指数降低者Trp64Arg频率低于体重指数下降不明显者。本研究结果提示ADRB3基因Trp64Arg突变与通过行为干预降低体重指数的困难有关，我们试图开发一种利用行为改变易感基因的多态性来预防生活方式相关疾病的方案。

The purpose of this study is development of susceptibility genes related to modification of living habit behavior for prevention of lifestyle related diseases. We named the gene a behavior modification susceptibility gene. We tried to develop a program for prevention of life-style related diseases.First, we investigated a association between smoking habit and the CYP2A6 gene polymorphism because nicotine is responsible for smoking dependence and is mainly metabolized by CYP2A6. Several types of genetic polymorphism of CYP2A6 have been reported. We clarified an association between CYP2A6 genotypes and smoking habit, cessation of smoking.The percentage of subjects with a CYP2A6de1 allele (genotype D) was lower in heavy smokers (22%, n=20) than in light smokers and non smokers (35%, n=40). The frequency of was lower in persons stopped smoking than in persons could not stop smoking.Trp64Arg mutation in the beta 3-adrenergic receptor (ADRB3) gene is related with obesity but it is not clear that this mutation is associated with reduction of body weight. We investigated the response of reduction of body weight in Japanese men with Trp64Arg mutation in the ADRB3 gene. At the baseline of BMI, there was no significant difference in participants with/without mutation of the ADRB3 gene. The frequency of Trp64Arg is lower in the persons reduced BMI than in the persons could not reduce BMI significantly. The results of this study suggest that the Trp64Arg mutation of the ADRB3 gene is associated with difficulty in reduction of BMI through behavioral intervention.We tried to develop a program to prevent of life-style related diseases using behavior modification susceptibility gene polymorphisms.