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

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.