DOI QR코드

DOI QR Code

건강한 성인의 glutathione S-transferase M1과 T1 유전자 다형성에 따른 한식에서의 식물성 식품군과 한식의 DNA 손상 감소 효과

Effects of lymphocyte DNA damage levels in Korean plant food groups and Korean diet regarding to glutathione S-transferase M1 and T1 polymorphisms

  • 김현아 (한남대학교 대덕밸리캠퍼스 생명나노과학대학 식품영양학과) ;
  • 이민영 (한남대학교 대덕밸리캠퍼스 생명나노과학대학 식품영양학과) ;
  • 강명희 (한남대학교 대덕밸리캠퍼스 생명나노과학대학 식품영양학과)
  • Kim, Hyun-A (Department of Food & Nutrition, Daedeok Valley Campus, Hannam University) ;
  • Lee, Min-Young (Department of Food & Nutrition, Daedeok Valley Campus, Hannam University) ;
  • Kang, Myung-Hee (Department of Food & Nutrition, Daedeok Valley Campus, Hannam University)
  • 투고 : 2017.01.13
  • 심사 : 2017.02.10
  • 발행 : 2017.02.28

초록

본 연구는 건강한 성인 남녀를 대상으로 glutathione S-transferase (GST)M1 및 T1 유전자 다형성에 따라 한식에서 주로 섭취하는 식물성 식품군과 한식 식단의 DNA 손상 감소효과를 측정하여 유전적 민감도가 어떻게 나타나는지를 알아보기 위해 수행되었다. 이를 위하여 건강한 성인 남녀 59명을 대상으로 혈액을 채취하여 GST genotype을 분류하였으며 그 중 17명을 선발하여 DNA 손상 감소효과를 Comet assay를 이용하여 측정하였고 DNA damage relative score로 나타냈다. 제 5기 2차년도 국민건강영양조사를 활용하여 한국인이 많이 섭취하는 식물성 식품을 10가지 식품군 (감자류, 견과류, 곡류, 과일류, 김치류, 두류, 버섯류, 오일류 채소류 해조류)으로 분류 후, 각 식품군별 총 섭취량의 1% 이상을 섭취한 84종의 식품을 한식 식물성 식품으로 최종 선정하였으며 한식 식단 (Korean diet)은 한국영양학회에서 발행한 [2010 한국인 영양섭취 기준]에 제시되어 있는 1주일 표준식단 (2,000 kcal/day)을 사용하였다. GSTM1 유전자 다형성에 따른 한식 식물성 식품군의 Tail moment로 본 DNA 손상 감소효과는 곡류와 오일류에서만 GSTM1 wild type보다 mutant type에서 유의하게 높았다. 이에 비해 DNA 손상 감소 효과를 % DNA in tail과 Tail moment로 본 결과, 견과류 과일류 채소류 버섯류 김치류 해조류에서 GSTT1 mutant type에 비해 wild type에서 유의하게 더 높게 나타났다. GSTM1과 GSTT1의 combined genotype에 따라 한식 식물성 식품의 DNA 손상 감소효과를 본 결과, 과일류, 김치류, 버섯류, 채소류, 해조류는 1군 (GSTM1+/GSTT1+) 및 3군 (GSTM1-/GSTT1+)에서, 오일류는 3군 (GSTM1-/GSTT1+)에서 DNA 손상 감소 효과가 유의하게 높았으며. 감자류, 견과류, 곡류, 두류, Total은 DNA 손상 감소 효과가 2군 (GSTM1+/GSTT1-) 및 3군 (GSTM1-/GSTT1+)에서 유의하게 높아 식품군에 따라 GST 유전자 다형성에 따른 DNA 손상 감소효과가 다르게 나타나는 것을 확인할 수 있었다. 한식 식단은 DNA 손상의 세 가지 지표인 % DNA in tail, Tail moment, Tail length로 측정해본 결과 GSTM1의 경우 wild type에서 mutant type보다 더 크게 나타났으며, GSTT1의 경우는 genotype에 따라 DNA 손상이 달라지는 경향은 있었지만 유의한 차이를 나타내지 않았다. 결론적으로 한식에서 주로 섭취하는 식물성 식품군에서는 식품에 따라 부분적으로 GSTM1은 mutant type에서, GSTT1은 wild type에서 DNA 손상 보호효과가 더 크게 나타났으며, GSTM1과 GSTT1의 combined genotype에 따른 DNA 손상 보호효과는 식품군에 따라 다르게 나타났다. 반면, 한식 식단에서는 DNA 손상 보호효과가 GSTM1 wild type에서 mutant type보다 더 크게 나타났으며, GSTT1 genotype에는 영향을 받지 않는 것으로 나타났다. 이와 같은 결과는 한식 식물성 식품군 및 식사패턴의 항산화 기능 우수성을 증명하는 기초자료가 될 것이며, 나아가 개인별 유전자에 따른 항산화 맞춤영양연구를 시작하는 시발점이 될 수 있을 것이다. 앞으로 GST 유전자 다형성에 따른 한식과 한식 식물성 식품군의 유전적 민감도를 더 명확하게 규명하기 위해서는 대상 인원을 늘려 수행하는 광범위한 연구가 필요할 것으로 보인다.

Purpose: GST (glutathione S-transferase) M1 and T1 gene polymorphisms are known to affect antioxidant levels. This study was carried out to evaluate genetic susceptibility by measuring the effect of DNA damage reduction in the Korean diet by vegetable food according to GST gene polymorphisms using the ex vivo method with human lymphocytes. Methods: Vegetable foods in the Korean diet based the results of the KNHANES V-2 (2011) were classified into 10 food groups. A total of 84 foods, which constituted more than 1% of the total intake in each food group, were finally designated as a vegetable food in the Korean diet. The Korean diet applied in this study is the standard one-week meals for Koreans (2,000 Kcal/day) suggested by the 2010 Dietary Reference Intakes for Koreans. Ex vivo DNA damage in human lymphocytes was assessed using comet assay. Results: In the Korean food group, the DNA damage protective effect of GSTM1 and GSTT1 was found to be greater in mutant type and wild-type, respectively. and the DNA damage protective effect according to the combined genotype of GSTM1 and GSTT1 was different depending on the food group. On the other hand, in Korean Diet, the DNA damage protective effect appeared to be larger in GSTM1 wild-type than in mutant type and was found to not be affected by GSTT1 genotype. Conclusion: These results can be used as basic data to demonstrate the superiority of the antioxidant function of Korean dietary patterns and food groups. Furthermore, it may be a starting point to begin research on customized antioxidant nutrition according to individual genes.

키워드

참고문헌

  1. Ministry of Health and Welfare, Korea Centers for Disease Control and Prevention. Korea Health Statistics 2015: Korea National Health and Nutrition Examination Survey (KNHANES VI-3). Sejong: Korea Centers for Disease Control and Prevention; 2016.
  2. Lee HS, Cho YH, Park J, Shin HR, Sung MK. Dietary intake of phytonutrients in relation to fruit and vegetable consumption in Korea. J Acad Nutr Diet 2013; 113(9): 1194-1199. https://doi.org/10.1016/j.jand.2013.04.022
  3. Lee JY. A study on planning the policy for the globalization of Korean food [dissertation]. Seoul: Chung-Ang University; 2009.
  4. Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP, Meyskens FL Jr, Valanis B, Williams JH Jr, Barnhart S, Cherniack MG, Brodkin CA, Hammar S. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst 1996; 88(21): 1550-1559. https://doi.org/10.1093/jnci/88.21.1550
  5. Park CH, Kim KH, Yook HS. Comparison of antioxidant and antimicrobial activities of bracken (Pteridium aquilinum Kuhn) according to cooking methods. Korean J Food Nutr 2014; 27(3): 348-357. https://doi.org/10.9799/ksfan.2014.27.3.348
  6. Lee MY, Han JH, Kang MH. Protective effect of Korean diet food groups on lymphocyte DNA damage and contribution of each food group to total dietary antioxidant capacity (TDAC). J Nutr Health 2016; 49(5): 277-287. https://doi.org/10.4163/jnh.2016.49.5.277
  7. Lee MY, Kim HA, Kang MH. Comparison of lymphocyte DNA damage levels and total antioxidant capacity in Korean and American diet. Nutr Res Pract 2017; 11(1): 33. https://doi.org/10.4162/nrp.2017.11.1.33
  8. Park YK, Park E, Kim JS, Kang MH. Daily grape juice consumption reduces oxidative DNA damage and plasma free radical levels in healthy Koreans. Mutat Res 2003; 529(1-2): 77-86. https://doi.org/10.1016/S0027-5107(03)00109-X
  9. Pool-Zobel BL, Bub A, Muller H, Wollowski I, Rechkemmer G. Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods. Carcinogenesis 1997; 18(9): 1847-1850. https://doi.org/10.1093/carcin/18.9.1847
  10. Sinha R, Caporaso N. Diet, genetic susceptibility and human cancer etiology. J Nutr 1999; 129(2S Suppl): 556S-559S. https://doi.org/10.1093/jn/129.2.556S
  11. Cho MR, Han JH, Lee HJ, Park YK, Kang MH. Purple grape juice supplementation in smokers and antioxidant status according to different types of GST polymorphisms. J Clin Biochem Nutr 2015; 56(1): 49-56. https://doi.org/10.3164/jcbn.14-1
  12. Cho HJ, Lee SY, Ki CS, Kim JW. GSTM1, GSTT1 and GSTP1 polymorphisms in the Korean population. J Korean Med Sci 2005; 20(6): 1089-1092. https://doi.org/10.3346/jkms.2005.20.6.1089
  13. Rebbeck TR. Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 1997; 6(9): 733-743.
  14. Saura-Calixto F, Goñi I. Antioxidant capacity of the Spanish Mediterranean diet. Food Chem 2006; 94(3): 442-447. https://doi.org/10.1016/j.foodchem.2004.11.033
  15. Han JH, Lee HJ, Cho MR, Chang N, Kim Y, Oh SY, Kang MH. Total antioxidant capacity of the Korean diet. Nutr Res Pract 2014; 8(2): 183-191. https://doi.org/10.4162/nrp.2014.8.2.183
  16. Hofmann T, Kuhnert A, Schubert A, Gill C, Rowland IR, Pool-Zobel BL, Glei M. Modulation of detoxification enzymes by watercress: in vitro and in vivo investigations in human peripheral blood cells. Eur J Nutr 2009; 48(8): 483-491. https://doi.org/10.1007/s00394-009-0039-5
  17. Lampe JW, Chen C, Li S, Prunty J, Grate MT, Meehan DE, Barale KV, Dightman DA, Feng Z, Potter JD. Modulation of human glutathione S-transferases by botanically defined vegetable diets. Cancer Epidemiol Biomarkers Prev 2000; 9(8): 787-793.
  18. Kim SJ, Kim MG, Kim KS, Song JS, Yim SV, Chung JH. Impact of glutathione S-transferase M1 and T1 gene polymorphisms on the smoking-related coronary artery disease. J Korean Med Sci 2008; 23(3): 365-372. https://doi.org/10.3346/jkms.2008.23.3.365
  19. Yu Y, Song Y. Three clustering patterns among metabolic syndrome risk factors and their associations with dietary factors in Korean adolescents: based on the Korea National Health and Nutrition Examination Survey of 2007-2010. Nutr Res Pract 2015; 9(2): 199-206. https://doi.org/10.4162/nrp.2015.9.2.199
  20. Woo HD, Shin A, Kim J. Dietary patterns of Korean adults and the prevalence of metabolic syndrome: a cross-sectional study. PLoS One 2014; 9(11): e111593. https://doi.org/10.1371/journal.pone.0111593
  21. The Korean Nutrition Society. Dietary referece intakes for Koreans. 1st rev. ed. Seoul: The Korean Nutrition Society; 2010.
  22. Lee SG, Oh SC, Jang JS. Antioxidant activities of citrus unshiu extracts obtained from different solvents. Korean J Food Nutr 2015; 28(3): 458-464. https://doi.org/10.9799/ksfan.2015.28.3.458
  23. Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor JB. Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 1994; 300(Pt 1): 271-276. https://doi.org/10.1042/bj3000271
  24. Bell DA, Taylor JA, Paulson DF, Robertson CN, Mohler JL, Lucier GW. Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst 1993; 85(14): 1159-1164. https://doi.org/10.1093/jnci/85.14.1159
  25. Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988; 175(1): 184-191. https://doi.org/10.1016/0014-4827(88)90265-0
  26. Riso P, Martini D, Moller P, Loft S, Bonacina G, Moro M, Porrini M. DNA damage and repair activity after broccoli intake in young healthy smokers. Mutagenesis 2010; 25(6): 595-602. https://doi.org/10.1093/mutage/geq045
  27. Marotta F, Weksler M, Naito Y, Yoshida C, Yoshioka M, Marandola P. Nutraceutical supplementation: effect of a fermented papaya preparation on redox status and DNA damage in healthy elderly individuals and relationship with GSTM1 genotype: a randomized, placebo-controlled, cross-over study. Ann N Y Acad Sci 2006; 1067(1): 400-407. https://doi.org/10.1196/annals.1354.057
  28. Gasper AV, Al-Janobi A, Smith JA, Bacon JR, Fortun P, Atherton C, Taylor MA, Hawkey CJ, Barrett DA, Mithen RF. Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli. Am J Clin Nutr 2005; 82(6): 1283-1291. https://doi.org/10.1093/ajcn/82.6.1283
  29. Lampe JW. Interindividual differences in response to plant-based diets: implications for cancer risk. Am J Clin Nutr 2009; 89(5): 1553S-1557S. https://doi.org/10.3945/ajcn.2009.26736D
  30. Yuan L, Ma W, Liu J, Meng L, Liu J, Li S, Han J, Liu Q, Feng L, Wang C, Xiao R. Effects of GSTM1/GSTT1 gene polymorphism and fruit & vegetable consumption on antioxidant biomarkers and cognitive function in the elderly: a community based cross-sectional study. PLoS One 2014; 9(11): e113588. https://doi.org/10.1371/journal.pone.0113588
  31. Hakim IA, Harris RB, Chow HH, Dean M, Brown S, Ali IU. Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers: role of glutathione S-transferase genotypes. Cancer Epidemiol Biomarkers Prev 2004; 13(2): 242-249. https://doi.org/10.1158/1055-9965.EPI-03-0193
  32. Tang JJ, Wang MW, Jia EZ, Yan JJ, Wang QM, Zhu J, Yang ZJ, Lu X, Wang LS. The common variant in the GSTM1 and GSTT1 genes is related to markers of oxidative stress and inflammation in patients with coronary artery disease: a case-only study. Mol Biol Rep 2010; 37(1): 405-410. https://doi.org/10.1007/s11033-009-9877-8
  33. Wilms LC, Boots AW, de Boer VC, Maas LM, Pachen DM, Gottschalk RW, Ketelslegers HB, Godschalk RW, Haenen GR, van Schooten FJ, Kleinjans JC. Impact of multiple genetic polymorphisms on effects of a 4-week blueberry juice intervention on ex vivo induced lymphocytic DNA damage in human volunteers. Carcinogenesis 2007; 28(8): 1800-1806. https://doi.org/10.1093/carcin/bgm145
  34. Wilms LC, Claughton TA, de Kok TM, Kleinjans JC. GSTM1 and GSTT1 polymorphism influences protection against induced oxidative DNA damage by quercetin and ascorbic acid in human lymphocytes in vitro. Food Chem Toxicol 2007; 45(12): 2592-2596. https://doi.org/10.1016/j.fct.2007.06.031
  35. Valerio LG Jr, Kepa JK, Pickwell GV, Quattrochi LC. Induction of human NAD(P)H:quinone oxidoreductase (NQO1) gene expression by the flavonol quercetin. Toxicol Lett 2001; 119(1): 49-57. https://doi.org/10.1016/S0378-4274(00)00302-7
  36. Seow A, Shi CY, Chung FL, Jiao D, Hankin JH, Lee HP, Coetzee GA, Yu MC. Urinary total isothiocyanate (ITC) in a population-based sample of middle-aged and older Chinese in Singapore: relationship with dietary total ITC and glutathione S-transferase M1/T1/P1 genotypes. Cancer Epidemiol Biomarkers Prev 1998; 7(9): 775-781.
  37. Visanji JM, Duthie SJ, Pirie L, Thompson DG, Padfield PJ. Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G2/M phase cell cycle arrest, DNA damage, and G2/M checkpoint activation. J Nutr 2004; 134(11): 3121-3126. https://doi.org/10.1093/jn/134.11.3121
  38. Pool-Zobel B, Veeriah S, Bohmer FD. Modulation of xenobiotic metabolising enzymes by anticarcinogens -- focus on glutathione S-transferases and their role as targets of dietary chemoprevention in colorectal carcinogenesis. Mutat Res 2005; 591(1-2): 74-92. https://doi.org/10.1016/j.mrfmmm.2005.04.020
  39. Yuan L, Zhang L, Ma W, Zhou X, Ji J, Li N, Xiao R. Glutathione S-transferase M1 and T1 gene polymorphisms with consumption of high fruit-juice and vegetable diet affect antioxidant capacity in healthy adults. Nutrition 2013; 29(7-8): 965-971. https://doi.org/10.1016/j.nut.2012.12.025
  40. Zhao B, Seow A, Lee EJ, Poh WT, Teh M, Eng P, Wang YT, Tan WC, Yu MC, Lee HP. Dietary isothiocyanates, glutathione S-transferase -M1, -T1 polymorphisms and lung cancer risk among Chinese women in Singapore. Cancer Epidemiol Biomarkers Prev 2001; 10(10): 1063-1067.
  41. Schroeder N, Park YH, Kang MS, Kim Y, Ha GK, Kim HR, Yates AA, Caballero B. A randomized trial on the effects of 2010 Dietary Guidelines for Americans and Korean diet patterns on cardiovascular risk factors in overweight and obese adults. J Acad Nutr Diet 2015; 115(7): 1083-1092. https://doi.org/10.1016/j.jand.2015.03.023
  42. Zamora-Ros R, Serafini M, Estruch R, Lamuela-Raventos RM, Martinez-Gonzalez MA, Salas-Salvado J, Fiol M, Lapetra J, Aros F, Covas MI, Andres-Lacueva C; PREDIMED Study Investigators. Mediterranean diet and non enzymatic antioxidant capacity in the PREDIMED study: evidence for a mechanism of antioxidant tuning. Nutr Metab Cardiovasc Dis 2013; 23(12): 1167-1174. https://doi.org/10.1016/j.numecd.2012.12.008
  43. Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, Gomez-Gracia E, Ruiz-Gutierrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pinto X, Basora J, Munoz MA, Sorli JV, Martinez JA, Martinez-Gonzalez MA; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013; 368(14): 1279-1290. https://doi.org/10.1056/NEJMoa1200303
  44. Chung J, Kwon SO, Ahn H, Hwang H, Hong SJ, Oh SY. Association between dietary patterns and atopic dermatitis in relation to GSTM1 and GSTT1 polymorphisms in young children. Nutrients 2015; 7(11): 9440-9452. https://doi.org/10.3390/nu7115473