Journal of Nutrition and Health

  • 제41권8호
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  • Pages.767-775
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  • 2008
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  • 2288-3886(pISSN)
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  • 2288-3959(eISSN)
한국영양학회 (The Korean Nutrition Society)
권호 표지

소아에서의 UCP-1 다형성과 비만도 및 혈액 지질수치와의 관련성에 관한 연구

The Relationships between UCP-1 Polymorphism and the Degree of Obesity or Plasma Lipid Profile in Prepubertal Children

  • 오현희 (가천의과학대학교 이길여암당뇨연구원 분자세포생리 및 대사실험실) ;
  • 신은정 (성신여자대학교 식품영양학과 영양생화학실) ;
  • 이명숙 (성신여자대학교 식품영양학과 영양생화학실)
  • Oh, Hyun-Hee (Department of Cellular & Molecular Physiology and Metabolism, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science) ;
  • Shin, Eun-Jung (Lab. in Nutritional Biochemistry, Department of Food and Nutrition, Sungshin Women's University) ;
  • Lee, Myoung-Sook (Lab. in Nutritional Biochemistry, Department of Food and Nutrition, Sungshin Women's University)
  • 발행 : 2008.12.31
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초록

1) 연구대상자 중 비만아동 빈도수 분석 결과, BIA법에서는 70.0%, BMI에 의한 비만도에서는 32.7%, 신장별 체중에 의한 비만도에서는 23.6%로 BAI법에 의해 비만아동의 빈도수가 가장 많았다. 혈청 생화화적 분석 결과는 NCEP의 이상지혈증 기준 이하로 나타났다. 2) UCP-1 유전자 다형성에 의한 신체계측의 결과의 분포는 정상형과 변이형에서 차이를 나타내지 않았고 혈중 생 화학 결과에서는 LDL (p = 0.039)과 TC (p = 0.063)이 정상형에 비해 변이형에서 유의적으로 증가하였다. 3) LDL을 130 mg/dL 기준으로 고LDL 콜레스테롤혈증과 정상으로 나누었을 때 각각에서 UCP-1 유전자 다형성의 분포는 고LDL 콜레스테롤혈증에서 A allele는 5.4%, G allele는 13.0%로 G allele의 빈도가 높게 분포하였고, 정상에서는 각각 94.6%, 87%의 분포를 나타내었다 (p = 0.062, ORs 2.640). LDL의 농도를 백분위수에 따라 4집단으로 나누고 UCP-1 유전자의 A allele와 G allele에서 LDL 농도의 빈도수를 나타내었을 때 G allele에서는 빈도수가 25th, 50th, 75th, 100th에 따라 유의적으로 증가하였다 ($r^2$ = 0.7995, p-trend = 0.032). 따라서 UCP-1 유전자 변이형은 정상형에 비해 고LDL-콜레스테롤혈증의 발병을 증가시키는 것으로 나타났다. UCP-1 유전자의 다형성은 이상지혈증의 위험인자인 LDL 농도를 증가시키는 위험요인으로써 나타났고, 체중을 감안할 때는 이상지혈증의 위험도가 더욱 증가할 것으로 생각되어진다. 따라서 UCP-1 유전자 변이형을 가지는 비만아동은 고LDL-콜레스테롤혈증의 발병과 관련된 식이 및 환경적 인자를 적절히 통제하는 예방 대책을 마련하여야겠다.

Uncoupling protein-1 (UCP-1) plays a major role in thermogenesis at brown adipose tissues and has been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of A-3826G polymorphism in 117 Korean prepubertal children aged 8-11 years olds. Anthropometry by bioelectrical impedance analysis method, plasma lipid profiles by auto-biochemical analyzer and UCP-1 genotyping by PCR-RFLP were done. The frequencies of UCP-1 genotypes were AA; 17.7%, AG; 57.8%, GG; 26.6%. The frequencies of each G allele (55.5%) was similar to Japanese's (49%) and higher than Caucacian's (25%). No correlation UCP-1 polymorphism and BMI (kg/$m^2$) or the degree of obesity described by the relative percentiles of the standard weight according to height in prepubertal children. However, plasma total- and LDL-cholesterol were significantly increased in G allele when sex, age and weight were adjusted. Our results suggested that G allele of UCP-1 gene was stronger risk factors in hyperLDLcholesterolemia than A allele. This impact might be progressed as the precaution against the revalence of obesity based-metabolic disease.

키워드

참고문헌

  1. Korea Institute for Health and Social Affairs. 2005 The Korean National Health and Nutrition Survey; 2006
  2. Ministry of Education & Human Resources Development. evaluation of adolescent health; 2003
  3. Koeppen-Schomerus G, Wardle J, Plomin R. A genetic analysis of weight and overweight in 4-year-old twin pairs. Int J Obes Relat Metab Disord 2001; 25(6): 838-844
  4. Romao I, Roth J. Genetic and environmental interactions in obesity and type 2 diabetes. J Am Diet Assoc 2008; 108: 24-28
  5. Echtay KS. Mitochondrial uncoupling proteins--what is their physiological role? Free Radic Biol Med 2007; 43(10): 1351-1371 https://doi.org/10.1016/j.freeradbiomed.2007.08.011
  6. Saito M, Ohashi A. Mitochondrial uncoupling protein as a target of pharmacotherapy for obesity. Nippon Yakurigaku Zasshi 2001; 118(5): 327 -333 https://doi.org/10.1254/fpj.118.327
  7. Bouillaud F, Couplan E, Pecqueur C, Ricquier D. Homologues of the uncoupling protein from brown adipose tissue (UCP-1): UCP2, UCP3, BMCP1 and UCP4. Biochim Biophys Acta 2001; 1504(1): 107-119 https://doi.org/10.1016/S0005-2728(00)00241-3
  8. Nakano T, Shinka T, Sei M, Sato Y, Umeno M, Sakamoto K, Nomura I, Nakahori Y. A/G heterozygote of the A-3826G polymorphism in the UCP-1 gene has higher BMI than A/A and G/G homozygote in young Japanese males. J Med Invest 2006; 53(3- 4): 218-222 https://doi.org/10.2152/jmi.53.218
  9. Hioki C, Yoshida T, Kogure A, Takakura Y, Umekawa T, Yoshioka K, Shimatsu A, Yoshikawa T. Effects of growth hormone (GH) on mRNA levels of uncoupling proteins 1, 2, and 3 in brown and white adipose tissues and skeletal muscle in obese mice. Horm Metab Res 2004; 36(9): 607-613 https://doi.org/10.1055/s-2004-825905
  10. Kahara T, Takamura T. Prediction of execise-mediated changes in metabolic markers by gene polymorphism. Diabetes Res Clin Pract 2002; 57(2): 105-110 https://doi.org/10.1016/S0168-8227(02)00023-2
  11. Garruti G, Ricquier D. Analysis of uncoupling protein and its mRNA in adipose tissue deposits of adult humans. Int J Obes Relat Metab Disord 1992; 16(5): 383-390
  12. Arner P. Hunting for human obesity genes? Look in the adipose tissue! Int J Obes Telat Metab Disord 2000; 4: 57-62
  13. Fumeron F, Durack-Bown I, Betoulle D, Cassard-Doulcier AM, Tuzet S, Bouillaud F, Melchior JC, Ricquier D, Apfelbaum M. Polymorphisms of uncoupling protein (UCP) and beta 3-adrenoreceptor genes in obese people submitted to a low calorie diet. Int J Obes Relat Metab Disord 1996: 20(12): 1051-1054
  14. Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 2007; 293(2): 444-452 https://doi.org/10.1152/ajpendo.00691.2006
  15. Tiraby C, Langin D. Conversion from white to brown adipocytes: a strategy for the control of fat mass? Trends Endocrinol Metab 2003;14(10): 439-441 https://doi.org/10.1016/j.tem.2003.10.001
  16. Nieman DC. Fitness and Sport Medicine: A Health-Related Approach. Bull Publishing Co, Palo Alto.; 1995
  17. Friedewald VE Jr, Gotto AM Jr. Case 1: a patient with elevated low-density lipoprotein cholesterol. Am J Cardiol 2000; 85(1): 131 https://doi.org/10.1016/S0002-9149(99)00801-2
  18. Yamazaki K, Murata M. Frequency of atherogenic risk factors in Japanese obese children. Diabetes Res Clin Pract 1990; 10(1): 211-219 https://doi.org/10.1016/0168-8227(90)90063-Y
  19. Zietz B, Watzlawek E, Palitzsch KD, Scholmerich J, Schaffler A. GG-genotype in the promotor region of uncoupling-protein-1 gene is associated with lower level of dehydroepiandrosterone in type 2 diabetes. Exp Clin Endocrinol Diabetes 2001; 109(2): 102-106 https://doi.org/10.1055/s-2001-14829
  20. Oh HH, Kim KS, Choi SM, Yang HS, Yoon Y. The effects of uncoupling protein-1 genotype on lipoprotein cholesterol level in Korean obese subjects. Metabolism 2004; 53(8): 1054-1059 https://doi.org/10.1016/j.metabol.2004.02.014
  21. Schaffler A, Palitzsch KD, Watzlawek E, Drobnik W, Schwer H, Scholmerich J, Schmitz G: Frequency and significance of the A →G (-3826) polymorphism in the promoter of the gene for uncoupling protein-1 with regard to metabolic parameters and adipocyte transcription factor binding in a large population-based Caucasian cohort. Eur J Clin Invest 1999; 29(9): 770-779 https://doi.org/10.1046/j.1365-2362.1999.00529.x
  22. Won HS, Han SS, Oh SY, Kim HY, Kim WK, Lee HS, Jang YA, Cho SS, Kim SH. Guidelines of body mass index in Korean childhood and adolescent obesity and relationship with physical strength. Korean J Nutr 2000; 33(3): 279-288
  23. Song YJ, Joung HJ, Kim YN, Paik HY. The physical development and dietary intake for Korean children and adolescents: body composition and obesity prevalence (1). Korean J Nutr 2006; 39(1): 44-49
  24. Lee SE, Kim HI, Yoon WS. Obesity evaluation by body mass index in elementary school children. Korea Sport Research 2004; 15(3): 1627- 1640
  25. Clement K, Ruiz J, Cassard-Doulcier AM, Bouillaud F, Ricquier D, Basdevant A, GuyGrand B, Froguel P. Additive effect of A→ G (-3826) variant of the uncoupling protein gene and the Trp- 64Arg mutation of the beta 3-adrenergic receptor gene on weight gain in morbid obesity. Int J Obes Relat Metab Disord 1996; 20(12): 1062-1066
  26. Herrmann SM, Wang JG, Staessen JA, Kertmen E, Schmidt- Petersen K, Zidek W, Paul M, Brand E. Uncoupling protein 1 and 3 polymorphisms are associated with waist-to-hip ratio. J Mol Med 2003; 81(5): 327-332 https://doi.org/10.1007/s00109-003-0431-1
  27. Heilbronn LK, Kind KL, Pancewicz E, Morris AM, Noakes M, Clifton PM. Association of -3826 G variant in uncoupling protein- 1 with increased BMI in overweight Australian women. Diabetologia 2000; 43(2): 242-244 https://doi.org/10.1007/s001250050036
  28. Gagnon J, Lago F, Chagnon YC, Perusse L, Naslund I, Lissner L, Sjostrom L, Bouchard C. DNA polymorphism in the uncoupling protein 1 (UCP-1) gene has no effect on obesity related phenotypes in the Swedish Obese Subjects cohorts. Int J Obes Relat Metab Disord 1998; 22(6): 500-505 https://doi.org/10.1038/sj.ijo.0800613
  29. Kim SG, Kim CH, Yun SK, Yun YI, Kim YH, Nam IS, Lee JY, Mok JO, Park HK, Kim YS, Byun DW, Suh KI, Yoo MH. Polymorphism of the uncoupling protein 1 gene and fatty acid binding protein 2 gene in Korean type 2 diabetic patients. J Korean Diabetes Assoc 2001; 25(4): 262-272
  30. Kim JH, Yun SK, Kim CH, Byun DW, Kim YS, Suh KI, Yoo MH. Association between uncoupling protein-1 and 3-adrenergic receptor gene polymorphisms and energy metabolism in normal Korean adults. J Korean Diabetes Assoc 1999; 23(6): 803-813
  31. Lee KY, Ju J, Rhee BO. A Study of the Relation between Food Habits, Anthropometric and Clinical Data in a Health Promoting Elementry School in Changwon. J Korean Dietetic Assoc 2001; 7(4): 331-348
  32. Lee JS, Lee JY, Im HJ, Jo ML, Cha SH, Jo YW. Comparisons of Anthropometric Measurements, Body Fat, Blood Parameters and Nutrients Intakes in Over- and Desirable-body Weight School Children. J Korean Dietetic Assoc 2000; 9(4): 316-325
  33. Kim KA, Kwun IS, Kwon CS. Potential Relationship between Children Obesity and Risk for Coronary Heart Disease in Kyungbuk Area. Korean J Nutr 2001; 34(6): 664-670
  34. Proenza AM, Poissonnet CM, Ozata M, Ozen S, Guran S, Palou A, Strosberg AD. Association of sets of alleles of genes encoding beta3-adrenoreceptor, uncoupling protein 1 and lipoprotein lipase with increased risk of metabolic complications in obesity. Int J Obes Relat Metab Disord 2000; 24(1): 93-100 https://doi.org/10.1038/sj.ijo.0801091
  35. The Asia-Pacific perspective: Redefining Obesity and its Treatment, WHO Western Pacific Region, International Association for the Study of Obesity, International Obesity Task Force; 2000
  36. Nagai N, Sakane N, Ueno LM, Hamada T, Moritani T. The -3826 A→G variant of the uncoupling protein-1 gene diminishes postprandial thermogenesis after a high fat meal in healthy boys. J Clin Endocrinol Metab 2003; 88(12): 5661-5667 https://doi.org/10.1210/jc.2003-030672
  37. Park MJ. Recent advances in regulating energy homeostasis and obesity. Korean J Pediatr 2005; 48(2): 126-137
  38. Lean ME, James WP, Jennings G, Trayhurn P. Brown adipose tissue uncoupling protein content in human infants, children and adults. Clin Sci (Lond) 1986; 71(3): 291-297 https://doi.org/10.1042/cs0710291
  39. Ricquier D. Respiration uncoupling and metabolism in the control of energy expenditure. Proc Nutr Soc 2005; 64(1): 47-52 https://doi.org/10.1079/PNS2004408
  40. Kotani K, Sakane N, Saiga K, Adachi S, Shimohiro H, Mu H, Kurozawa Y. Relationship between A-3826G polymorphism in the promoter of the uncoupling protein-1 gene and high-density lipoprotein cholesterol in Japanese individuals: a cross-sectional study. Arch Med Res 2008; 39(1): 142-146 https://doi.org/10.1016/j.arcmed.2007.07.002