title: NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modifies effects of cigarette smoking on risk of elevated levels of serum liver enzyme in male Japanese health check-up examinees: a cross-sectional study.
abstract: BACKGROUND
  NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism reportedly influences the effects of cigarette smoking on respiratory function, risk of dyslipidemia, serum non-high-density lipoprotein cholesterol levels, hematological parameters and intraocular pressure. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of cigarette smoking on serum liver enzyme levels in male Japanese health check-up examinees.
  
  
  METHODS
  A total of 421 male subjects (mean age ± SD, 54.1 ± 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After ND2-237 Leu/Met genotyping, a cross-sectional study assessing the combined effects of ND2-237 Leu/Met polymorphism and cigarette smoking on serum aspartate aminotransferase levels, serum alanine aminotransferase (ALT) levels and serum gamma-glutamyltransferase (GGT) levels was then conducted.
  
  
  RESULTS
  No statistically significant differences in serum liver enzyme levels among the three smoking status groups (never- or ex-smokers, 1-20 cigarettes smoked per day and >20 cigarettes smoked per day) by ND2-237 Leu/Met genotype were observed. However, for men with ND2-237Met, cigarette smoking significantly increased the risk of elevated levels of serum ALT (>30 U/L) or serum GGT (≥60 U/L or >51 U/L) (P for trend = 0.031, P for trend = 0.007 and P for trend = 0.004, respectively). After adjustment for age, body mass index, alcohol consumption, coffee consumption, antihypertensive treatment and antidiabetic treatment, a significant association between cigarette smoking and risk of elevated levels of serum ALT (>30 U/L) or serum GGT (≥60 U/L or >51 U/L) was also observed (P for trend = 0.032, P for trend = 0.019 and P for trend = 0.009, respectively). Surprisingly, for men with ND2-237Leu, cigarette smoking significantly decreased the risk of elevated levels of serum ALT (>30 U/L or ≥25 U/L) (P for trend = 0.026 and P for trend = 0.003, respectively).
  
  
  CONCLUSIONS
  Cigarette smoking appears to increase the risk of elevated levels of serum ALT or serum GGT in ND2-237Met genotypic men, but to decrease the risk of elevated levels of serum ALT in ND2-237Leu genotypic men.
authors.affiliation: Department of Public Health, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Akatsuki
authors.initials: A
authors.lastname: Kokaze
authors.affiliation: Department of Public Health, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Public Health, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan ; Mito Red Cross Hospital, 3-12-48 Sannomaru, Mito-shi, Ibaraki 310-0011, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Public Health, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Matsunaga
authors.affiliation: Department of Public Health, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Karita
authors.affiliation: Department of Public Health, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Ohtsu
authors.affiliation: Department of Public Health, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ochiai
authors.affiliation: Department of Public Health, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Shirasawa
authors.affiliation: Department of Public Health, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Hinako
authors.initials: H
authors.lastname: Nanri
authors.affiliation: Department of Public Health, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Baba
authors.affiliation: Department of Public Health, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hoshino
authors.affiliation: Department of Public Health, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takashima
keywords: Alanine aminotransferase; Cigarette smoking; Gamma-glutamyltransferase; Mitochondrial DNA polymorphism; NADH dehydrogenase; Reactive oxygen species