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，以预防生活方式相关疾病。我们将该基因命名为行为改变易感基因。我们试图制定一个预防生活方式相关疾病的计划。首先，我们调查了吸烟习惯和CYP 2A 6基因多态性之间的关联，因为尼古丁是吸烟依赖的原因，主要由CYP 2A 6代谢。CYP 2A 6的几种类型的遗传多态性已被报道。我们阐明了CYP 2A 6基因型与吸烟习惯和戒烟之间的关系，重度吸烟者中CYP 2A 6基因型D等位基因的比例（22%，n=20）低于轻度吸烟者和非吸烟者（35%，n=40）。结论：β 3-肾上腺素能受体（beta3-adrenergic receptor，ADRB 3）基因Trp 64 Arg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ADRB 3基因中Trp 64 Arg突变的日本男性体重减轻的反应。在BMI基线时，有/无ADRB 3基因突变的参与者没有显著差异。Trp 64 Arg在BMI降低者中的频率低于BMI不能显著降低者。本研究结果提示ADRB 3基因Trp 64 Arg突变与行为干预难以降低BMI有关，我们试图开发一种利用行为改变易感基因多态性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.