Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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TT Mutant Homozygote of Kruppel-like Factor 5 Is a Key Factor for Increasing Basal Metabolic Rate and Resting Metabolic Rate in Korean Elementary School Children

  • Choi, Jung Ran (Research Institute of Obesity Science, Sungshin Women's University) ;
  • Kwon, In-Su (Laboratory Exercise Biochemistry, Korea National Sport University) ;
  • Kwon, Dae Young (Nutrition and Metabolism Research Group, Korea Food Research Institute) ;
  • Kim, Myung-Sunny (Nutrition and Metabolism Research Group, Korea Food Research Institute) ;
  • Lee, Myoungsook (Research Institute of Obesity Science, Sungshin Women's University)
  • Received : 2013.07.17
  • Accepted : 2013.10.29
  • Published : 2013.12.31
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Abstract

We investigated the contribution of genetic variations of KLF5 to basal metabolic rate (BMR) and resting metabolic rate (RMR) and the inhibition of obesity in Korean children. A variation of KLF5 (rs3782933) was genotyped in 62 Korean children. Using multiple linear regression analysis, we developed a model to predict BMR in children. We divided them into several groups; normal versus overweight by body mass index (BMI) and low BMR versus high BMR by BMR. There were no differences in the distributions of alleles and genotypes between each group. The genetic variation of KLF5 gene showed a significant correlation with several clinical factors, such as BMR, muscle, low-density lipoprotein cholesterol, and insulin. Children with the TT had significantly higher BMR than those with CC (p=0.030). The highest muscle was observed in the children with TT compared with CC (p=0.032). The insulin and C-peptide values were higher in children with TT than those with CC (p=0.029 vs. p=0.004, respectively). In linear regression analysis, BMI and muscle mass were correlated with BMR, whereas insulin and C-peptide were not associated with BMR. In the high-BMR group, we observed that higher muscle, fat mass, and C-peptide affect the increase of BMR in children with TT (p < 0.001, p < 0.001, and p=0.018, respectively), while Rohrer's index could explain the usual decrease in BMR (adjust $r^2$=1.000, p < 0.001, respectively). We identified a novel association between TT of KLF5 rs3782933 and BMR in Korean children. We could make better use of the variation within KLF5 in a future clinical intervention study of obesity.

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References

  1. Oishi Y, Manabe I, Imai Y, Hara K, Horikoshi M, Fujiu K, et al. Regulatory polymorphism in transcription factor KLF5 at the MEF2 element alters the response to angiotensin II and is associated with human hypertension. FASEB J 2010;24:1780- 1788. https://doi.org/10.1096/fj.09-146589
  2. Gutierrez-Aguilar R, Benmezroua Y, Vaillant E, Balkau B, Marre M, Charpentier G, et al. Analysis of KLF transcription factor family gene variants in type 2 diabetes. BMC Med Genet 2007;8:53.
  3. Haldar SM, Ibrahim OA, Jain MK. Kruppel-like factors (KLFs) in muscle biology. J Mol Cell Cardiol 2007;43:1-10. https://doi.org/10.1016/j.yjmcc.2007.04.005
  4. Wu Z, Wang S. Role of kruppel-like transcription factors in adipogenesis. Dev Biol 2013;373:235-243. https://doi.org/10.1016/j.ydbio.2012.10.031
  5. Oishi Y, Manabe I, Tobe K, Tsushima K, Shindo T, Fujiu K, et al. Kruppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation. Cell Metab 2005;1:27-39. https://doi.org/10.1016/j.cmet.2004.11.005
  6. Banerjee SS, Feinberg MW, Watanabe M, Gray S, Haspel RL, Denkinger DJ, et al. The Kruppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-gamma expression and adipogenesis. J Biol Chem 2003;278:2581-2584. https://doi.org/10.1074/jbc.M210859200
  7. Watanabe N, Kurabayashi M, Shimomura Y, Kawai-Kowase K, Hoshino Y, Manabe I, et al. BTEB2, a Kruppel-like transcription factor, regulates expression of the SMemb/ Nonmuscle myosin heavy chain B (SMemb/NMHC-B) gene. Circ Res 1999;85:182-191. https://doi.org/10.1161/01.RES.85.2.182
  8. Hoshino Y, Kurabayashi M, Kanda T, Hasegawa A, Sakamoto H, Okamoto E, et al. Regulated expression of the BTEB2 transcription factor in vascular smooth muscle cells: analysis of developmental and pathological expression profiles shows implications as a predictive factor for restenosis. Circulation 2000;102:2528-2534. https://doi.org/10.1161/01.CIR.102.20.2528
  9. Gray S, Feinberg MW, Hull S, Kuo CT, Watanabe M, Sen-Banerjee S, et al. The Kruppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. J Biol Chem 2002;277:34322-34328. https://doi.org/10.1074/jbc.M201304200
  10. Zobel DP, Andreasen CH, Burgdorf KS, Andersson EA, Sandbaek A, Lauritzen T, et al. Variation in the gene encoding Kruppel-like factor 7 influences body fat: studies of 14 818 Danes. Eur J Endocrinol 2009;160:603-609. https://doi.org/10.1530/EJE-08-0688
  11. Sabounchi NS, Rahmandad H, Ammerman A. Best-fitting prediction equations for basal metabolic rate: informing obesity interventions in diverse populations. Int J Obes (Lond) 2013; 37:1364-1370. https://doi.org/10.1038/ijo.2012.218
  12. Wong JE, Poh BK, Nik Shanita S, Izham MM, Chan KQ, Tai MD, et al. Predicting basal metabolic rates in Malaysian adult elite athletes. Singapore Med J 2012;53:744-749.
  13. Hasson RE, Howe CA, Jones BL, Freedson PS. Accuracy of four resting metabolic rate prediction equations: effects of sex, body mass index, age, and race/ethnicity. J Sci Med Sport 2011;14:344-351. https://doi.org/10.1016/j.jsams.2011.02.010
  14. Pedersen SB, Nyholm B, Kristensen K, Nielsen MF, Schmitz O, Richelsen B. Increased adiposity and reduced adipose tissue mRNA expression of uncoupling protein-2 in first-degree relatives of type 2 diabetic patients: evidence for insulin stimulation of UCP-2 and UCP-3 gene expression in adipose tissue. Diabetes Obes Metab 2005;7:98-105. https://doi.org/10.1111/j.1463-1326.2005.00365.x
  15. Valve R, Heikkinen S, Rissanen A, Laakso M, Uusitupa M. Synergistic effect of polymorphisms in uncoupling protein 1 and beta3-adrenergic receptor genes on basal metabolic rate in obese Finns. Diabetologia 1998;41:357-361. https://doi.org/10.1007/s001250050915
  16. Compher C, Hise M, Sternberg A, Kinosian BP. Comparison between Medgem and Deltatrac resting metabolic rate measurements. Eur J Clin Nutr 2005;59:1136-1141. https://doi.org/10.1038/sj.ejcn.1602223
  17. Weir JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 1949;109:1-9.
  18. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
  19. Lauer RM, Lee J, Clarke WR. Factors affecting the relationship between childhood and adult cholesterol levels: the Muscatine Study. Pediatrics 1988;82:309-318.
  20. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-419. https://doi.org/10.1007/BF00280883
  21. Henry CJ. Basal metabolic rate studies in humans: measurement and development of new equations. Public Health Nutr 2005;8:1133-1152.
  22. Proenza AM, Poissonnet CM, Ozata M, Ozen S, Guran S, Palou A, et al. 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;24:93-100. https://doi.org/10.1038/sj.ijo.0801091
  23. Sipiläinen R, Uusitupa M, Heikkinen S, Rissanen A, Laakso M. Polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns. Diabetes 1997;46: 77-80.
  24. Suchanek P, Kralova-Lesna I, Poledne R, Lanska V, Hubacek JA. An AHSG gene variant modulates basal metabolic rate and body composition development after a short-time lifestyle intervention. Neuro Endocrinol Lett 2011;32 Suppl 2:32-36.
  25. Prokunina L, Alarcón-Riquelme ME. Regulatory SNPs in complex diseases: their identification and functional validation. Expert Rev Mol Med 2004;6:1-15.
  26. Miyake R, Ohkawara K, Ishikawa-Takata K, Morita A, Watanabe S, Tanaka S. Obese Japanese adults with type 2 diabetes have higher basal metabolic rates than non-diabetic adults. J Nutr Sci Vitaminol (Tokyo) 2011;57:348-354. https://doi.org/10.3177/jnsv.57.348
  27. Tverskaya R, Rising R, Brown D, Lifshitz F. Comparison of several equations and derivation of a new equation for calculating basal metabolic rate in obese children. J Am Coll Nutr 1998;17:333-336. https://doi.org/10.1080/07315724.1998.10718771
  28. Ramirez-Zea M. Validation of three predictive equations for basal metabolic rate in adults. Public Health Nutr 2005;8:1213- 1228.
  29. Miyake R, Tanaka S, Ohkawara K, Ishikawa-Takata K, Hikihara Y, Taguri E, et al. Validity of predictive equations for basal metabolic rate in Japanese adults. J Nutr Sci Vitaminol (Tokyo) 2011;57:224-232. https://doi.org/10.3177/jnsv.57.224
  30. Olive JL, Ballard KD, Miller JJ, Milliner BA. Metabolic rate and vascular function are reduced in women with a family history of type 2 diabetes mellitus. Metabolism 2008;57:831-837. https://doi.org/10.1016/j.metabol.2008.01.028
  31. Johnson AM, Olefsky JM. The origins and drivers of insulin resistance. Cell 2013;152:673-684. https://doi.org/10.1016/j.cell.2013.01.041
  32. Mehairi AE, Khouri AA, Naqbi MM, Muhairi SJ, Maskari FA, Nagelkerke N, et al. Metabolic syndrome among Emirati adolescents: a school-based study. PLoS One 2013;8:e56159. https://doi.org/10.1371/journal.pone.0056159

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