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Cigarette smoking, N-acetyltransferase 2 polymorphisms and systemic lupus erythematosus in a Japanese population

Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japanchikako{at}phealth.med.kyushu-u.ac.jp

M Washio

Department of Community Health and Clinical Epidemiology, St. Mary’s College, Kurume, Japan

T Horiuchi

Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Y Tada

Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan

T Asami

Rehabilitation Center, Saga Medical School Hospital, Saga, Japan

S Ide

Department of Community Health and Clinical Epidemiology, St. Mary’s College, Kurume, Japan

H Takahashi

Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan

G Kobashi

Molecular Biostatistics Research Team, Research Center for Charged Particle Therapy, National Institute of Radiological Science, Chiba, Japan

The Kyushu Sapporo SLE (KYSS) Study Group

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.

Key Words: epidemiology • NAT2 • smoking • systemic lupus erythematosus

Lupus, Vol. 18, No. 7, 630-638 (2009)
DOI: 10.1177/0961203309102809


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