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

Chikako Kiyohara, Masakazu Washio, T. Horiuchi, Y. Tada, T. Asami, S. Ide, H. Takahashi, G. Kobashi, Hiroko Kodama, Koichi Akashi, Mine Harada, Hiroshi Tsukamoto, Takao Hotokebuchi, Kohei Nagasawa, Osamu Ushiyama, Mitsuru Mori, Asae Oura, Yasuhisa Sinomura, Hiromu Suzuki, Motohisa YamamotoTakashi Abe, Hisato Tanaka, Norihiko Nogami, Kazushi Okamoto, Naomasa Sakamoto, Satoshi Sasaki, Yoshihiro Miyake, Tetsuji Yokoyama, Yutaka Inaba, Masaki Nagai

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Abstract

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.

Original languageEnglish
Pages (from-to)630-638
Number of pages9
JournalLupus
Volume18
Issue number7
DOIs
Publication statusPublished - Jan 1 2009

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Acetyltransferases
Systemic Lupus Erythematosus
Smoking
Population
Genotype
Odds Ratio
Confidence Intervals
Amines
Alleles
Gene-Environment Interaction
Smoke
Restriction Fragment Length Polymorphisms
Carcinogens
Tobacco
Phenotype
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Rheumatology

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Cigarette smoking, N-acetyltransferase 2 polymorphisms and systemic lupus erythematosus in a Japanese population. / Kiyohara, Chikako; Washio, Masakazu; Horiuchi, T.; Tada, Y.; Asami, T.; Ide, S.; Takahashi, H.; Kobashi, G.; Kodama, Hiroko; Akashi, Koichi; Harada, Mine; Tsukamoto, Hiroshi; Hotokebuchi, Takao; Nagasawa, Kohei; Ushiyama, Osamu; Mori, Mitsuru; Oura, Asae; Sinomura, Yasuhisa; Suzuki, Hiromu; Yamamoto, Motohisa; Abe, Takashi; Tanaka, Hisato; Nogami, Norihiko; Okamoto, Kazushi; Sakamoto, Naomasa; Sasaki, Satoshi; Miyake, Yoshihiro; Yokoyama, Tetsuji; Inaba, Yutaka; Nagai, Masaki.

In: Lupus, Vol. 18, No. 7, 01.01.2009, p. 630-638.

Research output: Contribution to journalArticle

Kiyohara, C, Washio, M, Horiuchi, T, Tada, Y, Asami, T, Ide, S, Takahashi, H, Kobashi, G, Kodama, H, Akashi, K, Harada, M, Tsukamoto, H, Hotokebuchi, T, Nagasawa, K, Ushiyama, O, Mori, M, Oura, A, Sinomura, Y, Suzuki, H, Yamamoto, M, Abe, T, Tanaka, H, Nogami, N, Okamoto, K, Sakamoto, N, Sasaki, S, Miyake, Y, Yokoyama, T, Inaba, Y & Nagai, M 2009, 'Cigarette smoking, N-acetyltransferase 2 polymorphisms and systemic lupus erythematosus in a Japanese population', Lupus, vol. 18, no. 7, pp. 630-638. https://doi.org/10.1177/0961203309102809
Kiyohara, Chikako ; Washio, Masakazu ; Horiuchi, T. ; Tada, Y. ; Asami, T. ; Ide, S. ; Takahashi, H. ; Kobashi, G. ; Kodama, Hiroko ; Akashi, Koichi ; Harada, Mine ; Tsukamoto, Hiroshi ; Hotokebuchi, Takao ; Nagasawa, Kohei ; Ushiyama, Osamu ; Mori, Mitsuru ; Oura, Asae ; Sinomura, Yasuhisa ; Suzuki, Hiromu ; Yamamoto, Motohisa ; Abe, Takashi ; Tanaka, Hisato ; Nogami, Norihiko ; Okamoto, Kazushi ; Sakamoto, Naomasa ; Sasaki, Satoshi ; Miyake, Yoshihiro ; Yokoyama, Tetsuji ; Inaba, Yutaka ; Nagai, Masaki. / Cigarette smoking, N-acetyltransferase 2 polymorphisms and systemic lupus erythematosus in a Japanese population. In: Lupus. 2009 ; Vol. 18, No. 7. pp. 630-638.
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AU - Washio, Masakazu

AU - Horiuchi, T.

AU - Tada, Y.

AU - Asami, T.

AU - Ide, S.

AU - Takahashi, H.

AU - Kobashi, G.

AU - Kodama, Hiroko

AU - Akashi, Koichi

AU - Harada, Mine

AU - Tsukamoto, Hiroshi

AU - Hotokebuchi, Takao

AU - Nagasawa, Kohei

AU - Ushiyama, Osamu

AU - Mori, Mitsuru

AU - Oura, Asae

AU - Sinomura, Yasuhisa

AU - Suzuki, Hiromu

AU - Yamamoto, Motohisa

AU - Abe, Takashi

AU - Tanaka, Hisato

AU - Nogami, Norihiko

AU - Okamoto, Kazushi

AU - Sakamoto, Naomasa

AU - Sasaki, Satoshi

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AU - Inaba, Yutaka

AU - Nagai, Masaki

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