Tailor-made therapy for smoking cessation by genetic analysis of smoking-related genes in Japanese

我们检测了日本吸烟者(n=200)中CYP2A6^*4、^*7和^*9三种基因型与吸烟习惯的关系。^*1、^*4、^*7和^*9的频率分别为52、17、11、20%。当^*4、^*7、^*9为1个缺陷等位基因时，野生型、杂合子、纯合子突变率分别为26.0%、52.5%、21.5%。与杂合子或野生型相比，纯合子突变的受试者每天吸烟更少。日吸烟量以^*1/^*1最多，^*4/^*4最少，其余各型按等位基因缺陷数分布。已有研究表明，5-羟色胺转运体(5-HTT)启动子基因多态性与吸烟习惯和肺动脉重构有关。我们评估了该基因多态与吸烟行为、肺功能和胸部CT表现的关系。S/S 127例，S/L 61例，L/L 9例。与L组(S/L，L/L)相比，S组(S/S)每天吸烟和终生吸烟的次数多(P<0.05和P<0.01)，吸烟持续时间长(P<0.01)。此外，S组的肺气肿改变明显多于L组(P=0.0 1)，而%DL；提示5-HTT基因多态性与吸烟习惯有关，通过限制吸烟影响肺气肿的发生。尼古丁通过刺激多巴胺能神经元分泌多巴胺而导致烟草依赖。在多巴胺D2受体TaqI A1/A2多态分析中，A1/A29%、A1/A249%、A2/A242%。COPD患者与健康吸烟者的等位基因频率无明显差异。虽然吸烟习惯在A1/A1组间无差异，但A1/A1组的%VC和%FEV1显著高于A2/A2组(P<0.05)。D2A1/2多态与肺功能相关，与吸烟量无关。

We examined the relationship between the genotypes of CYP2A6^*4,^*7, and ^*9 and smoking habits in Japanese smokers (n=200). Frequencies of ^*1,^*4,^*7, and ^*9 were 52,17,11,20%. When ^*4,^*7, and ^*9 were regarded as one defective allele, percentages of wild type, heterozygote, homozygous mutant were 26.0,52.5,21.5%,respectively. Subjects with the homozygous mutant smoked fewer cigarettes/day compared with the heterozygote or wild type. Daily cigarette consumption was most in ^*1/^*1 and fewest in ^*4/^*4, and the other genotypes were located according to the number of defective alleles. It was reported that serotonin transporter (5-HTT) promoter polymorphism was associated with smoking habit and remodeling of pulmonary arteries. We evaluated the relationship between this polymorphism and smoking behaviors, pulmonary functions, and chest-CT findings. The numbers of subjects with each genotype were S/S 127,S/L 61, and L/L 9. Daily and lifelong cigarette consumption was more (p<0.05 and <0.01) and smoking duration was longer (p<0.01) in S group (S/S) compared with L group (S/L, L/L). In addition emphysematous changes were more (p=0.01) and %DL_<co> was lower (p<0.05) in S group than L group. These results suggested that the 5-HTT polymorphism was related to smoking habits affecting the development of emphysema through limiting cigarette consumption. Nicotine is responsible for tobacco dependence by stimulating dopaminergic neurons to secrete dopamine. In the analysis of dopamine D2 receptor TaqI A1/A2 polymorphism, the genotype frequencies were A1/A1 9%, A1/A2 49%, A2/A2 42%. There was no difference in the allele frequency between COPD patients and healthy smokers. Although smoking habits did not differ between the genotypes, %VC and %FEV1 were higher in A1/A1 group than A2/A2 group (p<0.05). The D2 A1/2 polymorphism was associated with pulmonary functions regardless of the amount of smoking.