量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果(学会誌発表論文、学会発表、研究開発報告書、特許等)を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Cigarette smoking may be associated with an increased risk of systemic lupus erythematosus (SLE), but the underlying mechanism of this association remains unclear. N-acetyltransferase 2 (NAT2) is highly variable and detoxifies aromatic amines, an important class of carcinogens in tobacco smoke. Individuals who possess homozygous polymorphic alleles have a slower rate of metabolic detoxification of aromatic amines. We investigated the relationship of the NAT2 polymorphism to the risk of SLE with special reference to the interaction with cigarette smoking among 152 SLE cases and 427 controls in a female Japanese population. NAT2 4, NAT2 5B, NAT2 6A and NAT2 7B alleles were detected with polymerase chain reaction-restriction fragment length polymorphism. Individuals carrying the 4/4 genotype are rapid acetylators, whereas those with homozygous non- 4 genotypes have a slow acetylator phenotype. Cigarette smoking was associated with an increased risk of SLE (odds ratio [OR] = 2.26; 95% confidence interval [CI] = 1.46-3.50). The slow acetylator genotype of NAT2 was significantly associated with an increased risk of SLE (OR = 2.34, 95% CI = 1.21-4.52) compared with the rapid acetylator genotype. A gene-environment interaction was suggested, with a combination of the NAT2 slow acetylator genotype and smoking conferring significantly higher risk (OR = 6.44, 95% CI = 3.07-13.52; attributable proportion due to interaction = 0.50, 95% CI = 0.12-0.88), compared with the NAT2 rapid acetylator genotype and no history of smoking. This study suggests that, in this Japanese population, the NAT2 slow acetylator status may be a determinant in susceptibility to SLE.