RESEARCH PAPER
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
 
More details
Hide details
1
Department of Public Health, Showa University School of Medicine, Shinagawa-ku, Japan
2
Department of Public Health, Kyorin University School of Medicine, Mitaka-shi, Japan
3
Mito Red Cross Hospital, Mito-shi, Japan
CORRESPONDING AUTHOR
Akatsuki Kokaze   

Department of Public Health, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Publish date: 2014-07-10
 
Tobacco Induced Diseases 2014;12(July):11
KEYWORDS
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.

 
REFERENCES (37)
1.
Altamirano J, Bataller R: Cigarette smoking and chronic liver diseases. Gut. 2010, 59: 1159-1162. 10.1136/gut.2008.162453.
 
2.
El-Zayadi AR: Heavy smoking and liver. World J Gastroenterol. 2006, 12: 6098-6101.
 
3.
Wang CS, Wang ST, Chang TT, Yao WJ, Chou P: Smoking and alanine aminotransferase levels in hepatitis C virus infection: implications for prevention of hepatitis C virus progression. Arch Intern Med. 2002, 162: 811-815. 10.1001/archinte.162.7.811.
 
4.
Nakanishi N, Nakamura K, Suzuki K, Tatara K: Lifestyle and serum gamma-glutamyltransferase: a study of middle-aged Japanese men. Occup Med (Lond). 2000, 50: 115-120. 10.1093/occmed/50.2.115.
 
5.
Nakanishi N, Nakamura K, Suzuki K, Tatara K: Lifestyle and the development of increased serum gamma-glutamyltransferase in middle-aged Japanese men. Scand J Clin Lab Invest. 2000, 60: 429-438. 10.1080/003655100448400.
 
6.
Higashikawa A, Suwazono Y, Okubo Y, Uetani M, Kobayashi E, Kido T, Nogawa K: Association of working conditions and lifestyle with increased serum gamma-glutamyltransferase: a follow-up study. Arch Med Res. 2005, 36: 567-573. 10.1016/j.arcmed.2005.03.027.
 
7.
Jang ES, Jeong SH, Hwang SH, Kim HY, Ahn SY, Lee J, Lee SH, Park YS, Hwang JH, Kim JW, Kim N, Lee DH: Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study. BMC Gastroenterol. 2012, 12: 145-10.1186/1471-230X-12-145.
 
8.
Tanaka M, Gong JS, Zhang J, Yoneda M, Yagi K: Mitochondrial genotype associated with longevity. Lancet. 1998, 351: 185-186. 10.1016/S0140-6736(05)78211-8.
 
9.
Kokaze A, Ishikawa M, Matsunaga N, Yoshida M, Satoh M, Teruya K, Masuda Y, Honmyo R, Uchida Y, Takashima Y: NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modifies the effects of alcohol consumption on risk for hypertension in middle-aged Japanese men. Hypertens Res. 2007, 30: 213-218. 10.1291/hypres.30.213.
 
10.
Wang D, Taniyama M, Suzuki Y, Katagiri T, Ban Y: Association of the mitochondrial DNA 5178 A/C polymorphism with maternal inheritance and onset of type 2 diabetes in Japanese patients. Exp Clin Endocrinol Diabetes. 2001, 109: 361-364. 10.1055/s-2001-17407.
 
11.
Mukae S, Aoki S, Itoh S, Sato R, Nishio K, Iwata T, Katagiri T: Mitochondrial 5178A/C genotype is associated with acute myocardial infarction. Circ J. 2003, 67: 16-20. 10.1253/circj.67.16.
 
12.
Takagi K, Yamada Y, Gong JS, Sone T, Yokota M, Tanaka M: Association of a 5178C → A (Leu237Met) polymorphism in the mitochondrial DNA with a low prevalence of myocardial infarction in Japanese individuals. Atherosclerosis. 2004, 175: 281-286. 10.1016/j.atherosclerosis.2004.03.008.
 
13.
Ohkubo R, Nakagawa M, Ikeda K, Kodama T, Arimura K, Akiba S, Saito M, Ookatsu Y, Atsuchi Y, Yamano Y, Osame M: Cerebrovascular disorders and genetic polymorphisms: mitochondrial DNA5178C is predominant in cerebrovascular disorders. J Neurol Sci. 2002, 198: 31-35. 10.1016/S0022-510X(02)00055-2.
 
14.
Kokaze A, Ishikawa M, Matsunaga N, Yoshida M, Satoh M, Teruya K, Honmyo R, Shirasawa T, Hoshino H, Takashima Y: Longevity-associated mitochondrial DNA 5178 C/A polymorphism and its interaction with cigarette consumption are associated with pulmonary function in middle-aged Japanese men. J Hum Genet. 2007, 52: 680-685. 10.1007/s10038-007-0171-0.
 
15.
Kokaze A, Ishikawa M, Matsunaga N, Karita K, Yoshida M, Shimada N, Ohtsu T, Shirasawa T, Ochiai H, Satoh M, Hashimoto M, Hoshino H, Takashima Y: Mitochondrial DNA 5178 C/A polymorphism influences the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese men. Lipids Health Dis. 2012, 11: 97-10.1186/1476-511X-11-97.
 
16.
Kokaze A, Ishikawa M, Matsunaga N, Karita K, Yoshida M, Ohtsu T, Ochiai H, Shirasawa T, Nanri H, Hoshino H, Takashima Y: Difference in effects of cigarette smoking or alcohol consumption on serum non-high-density lipoprotein cholesterol levels is related to mitochondrial DNA 5178 C/A polymorphism in middle-aged Japanese men: a cross-sectional study. J Physiol Anthropol. 2014, 33: 1-10.1186/1880-6805-33-1.
 
17.
Kokaze A, Ishikawa M, Matsunaga N, Yoshida M, Makita R, Satoh M, Teruya K, Sekiguchi K, Masuda Y, Harada M, Uchida Y, Takashima Y: Interaction between longevity-associated mitochondrial DNA 5178 C/A polymorphism and cigarette smoking on hematological parameters in Japanese men. Arch Gerontol Geriatr. 2005, 40: 113-122. 10.1016/j.archger.2004.07.003.
 
18.
Kokaze A, Yoshida M, Ishikawa M, Matsunaga N, Makita R, Satoh M, Sekiguchi K, Masuda Y, Uchida Y, Takashima Y: Longevity-associated mitochondrial DNA 5178 A/C polymorphism is associated with intraocular pressure in Japanese men. Clin Experiment Ophthalmol. 2004, 32: 131-136. 10.1111/j.1442-9071.2004.00796.x.
 
19.
Kokaze A, Ishikawa M, Matsunaga N, Yoshida M, Sekine Y, Teruya K, Takeda N, Sumiya Y, Uchida Y, Takashima Y: Association of the mitochondrial DNA 5178 A/C polymorphism with serum lipid levels in the Japanese population. Hum Genet. 2001, 109: 521-525. 10.1007/s004390100602.
 
20.
Loomba R, Hwang SJ, O'Donnell CJ, Ellison RC, Vasan RS, D'Agostino RB, Liang TJ, Fox CS: Parental obesity and offspring serum alanine and aspartate aminotransferase levels: the Framingham heart study. Gastroenterology. 2008, 134: 953-959. 10.1053/j.gastro.2008.01.037.
 
21.
Parti D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, Zanuso F, Mozzi F, Milani S, Conte D, Colombo M, Sirchia G: Updated definitions of healthy ranges for serum alanine amonotrabsferase levels. Ann Intern Med. 2002, 137: 1-10. 10.7326/0003-4819-137-1-200207020-00006.
 
22.
Miyake T, Kumagi T, Hirooka M, Koizumi M, Furukawa S, Ueda T, Tokumoto Y, Ikeda Y, Abe M, Kitai K, Hiasa Y, Matusura B, Onji M: Metabolic markers and ALT cutoff level for diagnosing nonalcoholic fatty liver disease: a community-based cross-sectional study. J Gastroenterol. 2012, 47: 696-703. 10.1007/s00535-012-0534-y.
 
23.
Ruhl CE, Everhart JE: Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology. 2009, 136: 477-485. 10.1053/j.gastro.2008.10.052.
 
24.
Loomba R, Doycheva I, Bettencourt R, Cohen B, Wassel CL, Brenner D, Barrett-Connor E: Serum γ-glutamyltranspeptidase predicts all-cause, cardiovascular and liver mortality in older adults. J Clin Exp Hepatol. 2013, 3: 4-11. 10.1016/j.jceh.2012.10.004.
 
25.
Jo SK, Lee WY, Rhee EJ, Won JC, Jung CH, Park CY, Oh KW, Park SW, Kim SW: Serum gamma-glutamyl transferase activity predicts future development of metabolic syndrome defined by 2 different criteria. Clin Chim Acta. 2009, 403: 234-240. 10.1016/j.cca.2009.03.035.
 
26.
Sakuta H, Suzuki T, Yasuda H, Ito T: Gamma-glutamyl transferase and metabolic risk factors for cardiovascular disease. Intern Med. 2005, 44: 538-541. 10.2169/internalmedicine.44.538.
 
27.
Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults: Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002, 106: 3143-3421.
 
28.
Madamanchi NR, Runge MS: Mitochondrial dysfunction in atherosclerosis. Circ Res. 2007, 100: 460-473. 10.1161/01.RES.0000258450.44413.96.
 
29.
Gusdon AM, Votyakova TV, Mathews CE: mt-Nd2 a suppresses reactive oxygen species production by mitochondrial complexes I and III. J Biol Chem. 2008, 83: 10690-10697.
 
30.
Stadtman ER, Moskovitz J, Berlett BS, Levine RL: Cyclic oxidation and reduction or protein methionine residues is an important antioxidant mechanism. Mol Cell Biochem. 2002, 234–235: 3-9.
 
31.
Ambrose JA, Barua RS: The pathophysiology of cigarette smoking and cardiovascular disease: an update. J Am Coll Cardiol. 2004, 43: 1731-1737. 10.1016/j.jacc.2003.12.047.
 
32.
Lee DH, Blomhoff R, Jacobs DR: Is serum gamma glutamyltransferase a marker of oxidative stress?. Free Radic Res. 2004, 38: 535-539. 10.1080/10715760410001694026.
 
33.
Sakamoto T, Higaki Y, Hara M, Ichiba M, Horita M, Mizuta T, Eguchi Y, Yasutake T, Ozaki I, Yamamoto K, Onohara S, Kawazoe S, Shigematsu H, Koizumi S, Tanaka K: Interaction beween interleukin-1β –31 T/C gene polymorphism and drinking and smoking habits on the risk of hepatocellular carcinoma among Japanese. Cancer Lett. 2008, 271: 98-104. 10.1016/j.canlet.2008.05.036.
 
34.
Imaizumi T, Higaki Y, Hara M, Sakamoto T, Horita M, Mizuta T, Eguchi Y, Yasutake T, Ozaki I, Yamamoto K, Onohara S, Kawazoe S, Shigematsu H, Koizumi S, Kudo S, Tanaka K: Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population. Carcinogenesis. 2009, 30: 1729-1734. 10.1093/carcin/bgp191.
 
35.
Oniki K, Hori M, Saruwatari J, Morita K, Kajiwara A, Sakata M, Mihara S, Ogata Y, Nakagawa K: Interactive effects of smoking and glutathione S-transferase polymorphisms on the development of non-alcoholic fatty liver disease. Toxicol Lett. 2013, 220: 143-149. 10.1016/j.toxlet.2013.04.019.
 
36.
Zhang J, Wheeler DA, Yakub I, Wei S, Sood R, Rowe W, Liu PP, Gibbs RA, Buetow KH: SNPdetector: a software tool for sensitive and accurate SNP detection. PLoS Comput Biol. 2005, 1: e53-10.1371/journal.pcbi.0010053.
 
37.
Kokaze A, Ishikawa M, Matsunaga N, Karita K, Yoshida M, Shimada N, Ohtsu T, Shirasawa T, Ochiai H, Hoshino H, Takashima Y: Combined effect of mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on estimated glomerular filtration rate in male Japanese health check-up examinees: a cross-sectional study. BMC Nephrol. 2013, 14: 35-10.1186/1471-2369-14-35.
 
 
CITATIONS (2):
1.
Fine Particle Pollution, Alanine Transaminase, and Liver Cancer: A Taiwanese Prospective Cohort Study (REVEAL-HBV)
Wen-Chi Pan, Chih-Da Wu, Mu-Jean Chen, Yen-Tsung Huang, Chien-Jen Chen, Huey-Jen Su, Hwai-I Yang
JNCI: Journal of the National Cancer Institute
 
2.
Mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on elevated levels of serum liver enzymes in male Japanese health check-up examinees: an exploratory cross-sectional study
Akatsuki Kokaze, Masao Yoshida, Mamoru Ishikawa, Naomi Matsunaga, Kanae Karita, Hirotaka Ochiai, Takako Shirasawa, Hinako Nanri, Kiyomi Mitsui, Hiromi Hoshimo, Yutaka Takashima
Journal of Physiological Anthropology
 
eISSN:1617-9625