2006 Fiscal Year Final Research Report Summary
Tailor-made therapy for smoking cessation by genetic analysis of smoking-related genes in Japanese
| Project/Area Number |
17590804
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
NAKAMURA Hidetoshi Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (00217879)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIZAKA Akitoshi Keio University, School of Medicine, Professor, 医学部, 教授 (90176181)
KURIHARA Ako Keio University, School of Medicine, Assistant, 医学部, 助手 (80338037)
OGAWA Yuko Keio University, School of Medicine, Assistant, 医学部, 助手 (00348632)
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| Project Period (FY) |
2005 – 2006
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| Keywords | smoking / gene / nicotine / CYP2A6 / serotonin / dopamine |
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| Research Abstract |
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.
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