Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Genetic Association Study of $THR{\beta}$Polymorphisms with Obesity in Korean Population

  • Jung, Kyung-Hee (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Ban, Ju-Yeon (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Kim, Hak-Jae (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Park, Hae-Jung (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Uhm, Yoon-Kyung (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Kim, Su-Kang (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Kim, Bum-Shik (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Kim, Youn-Jung (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Koh, In-Song (Department of Physiology, College of Medicine, Han Yang University) ;
  • Chung, Joo-Ho (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University)
  • Published : 2008.06.30
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Abstract

The growing problem of obesity is associated with numerous medical conditions. Several studies have reported that activation of thyroid hormone receptor beta $(THR{\beta})$ is involved in lipid metabolism and thermogenesis. To identify the relationship between the $THR{\beta}$ gene and obesity, we genotyped eighty two single nucleotide polymorphisms (SNPs) in the gene using the Affymetrix array chip in 209 overweight/obese and 155 normal subjects in Korean population. Of the eighty two polymorphisms, the seven SNPs exhibited a significant association with overweight/obesity in three alternative models (codominant, dominant, and recessive models; P<0.05 after adjusting for age and sex) were rs826221 (+267878 T>C), rs4858604 (+186399 A>G), rs1158265 (+200152 T>C), rs1868575 (+206031 G>A), rs1700939 (+238467 T>A), rs1505301 (+241933 T>C), and rs1924768 (+126491 T>C). During haplotype analysis using HapAnalyzer software, 2 haplotypes (block 13: TTAT; block 15: CTGC) containing significant polymorphisms (rs1700939 +238467 T>A and rs4858604 +186399 A>G) were detected to be significantly different. The results suggest that the $THR{\beta}$ gene may be associated with overweight/obesity in Korean population.

Keywords

References

  1. Aronne, L. J. Epidemiology, morbidity, and treatment of overweight and obesity. J Clin Psychiatry 62:13-22 (2001)
  2. Bloomgarden, Z. T. Obesity and diabetes. Diabetes Care 23:1584-1590 (2000) https://doi.org/10.2337/diacare.23.10.1584
  3. Sachdev, H. S. et al. Anthropometric indicators of body composition in young adults: Relation to size at birth and serial measurements of body mass index in childhood in the new delhi birth cohort. Am J Clin Nutr 82:456-466 (2005) https://doi.org/10.1093/ajcn/82.2.456
  4. Faith, M. S. et al. Evidence for independent genetic influences on fat mass and body mass index in a pediatric twin sample. Pediatrics 104:61-67 (1999) https://doi.org/10.1542/peds.104.1.61
  5. Duarte, S. F. et al. P.Q223r leptin receptor polymorphism associated with obesity in brazilian multiethnic subjects. Am J Hum Biol 18:448-453 (2006) https://doi.org/10.1002/ajhb.20519
  6. Rankinen, T. et al. The human obesity gene map: The 2005 update. Obesity 14:529-644 (2006) https://doi.org/10.1038/oby.2006.71
  7. Roti, E., Minelli, R. & Salvi, M. Thyroid hormone metabolism in obesity. Int J Obes Relat Metab Disord 24:S113-115 (2000) https://doi.org/10.1038/sj/ijo/0801293
  8. Forrest, D. & Vennstrom, B. Functions of thyroid hormone receptors in mice. Thyroid 10:41-52 (2000) https://doi.org/10.1089/thy.2000.10.41
  9. Trost, S. U. et al. The thyroid hormone receptor-betaselective agonist gc-1 differentially affects plasma lipids and cardiac activity. Endocrinology 141:3057-3064 (2000) https://doi.org/10.1210/en.141.9.3057
  10. Glass, C. K. & Rosenfeld, M. G. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 14:121-141 (2000)
  11. Gauthier, K., Aubert, D., Chassande, O., Flamant, F. & Samarut, J. Null mutant mice for thyroid hormone receptors. Methods Mol Biol 202:13-29 (2002)
  12. Wondisford, F. E. Thyroid hormone action: Insight from transgenic mouse models. J Investig Med 51:215-220 (2003) https://doi.org/10.2310/6650.2003.39191
  13. Wikstrom, L. et al. Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1. EMBO J 17:455-461 (1998) https://doi.org/10.1093/emboj/17.2.455
  14. Gloss, B. et al. Cardiac ion channel expression and contractile function in mice with deletion of thyroid hormone receptor alpha or beta. Endocrinology 142: 544-550 (2001) https://doi.org/10.1210/en.142.2.544
  15. Storey, N. M. et al. Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone. Proc Natl Acad Sci U S A 103:5197-5201 (2006)
  16. Cao, X., Kambe, F., Moeller, L. C., Refetoff, S. & Seo, H. Thyroid hormone induces rapid activation of Akt/protein kinase B-mammalian target of rapamycinp70S6K cascade through phosphatidylinositol 3-kinase in human fibroblasts. Mol Endocrinol 19:102-112 (2005) https://doi.org/10.1210/me.2004-0093
  17. Kim, S. K., Zhang, K. & Sun, F. A comparison of different strategies for computing confidence intervals of the linkage disequilibrium measure D'. Pac Symp Biocomput 2004:128-139
  18. Lazar, M. A. & Berrodin, T. J. Thyroid hormone receptors form distinct nuclear protein-dependent and independent complexes with a thyroid hormone response element. Mol Endocrinol 4:1627-1635 (1990) https://doi.org/10.1210/mend-4-11-1627
  19. Yen, P. M., Wilcox, E. C. & Chin, W. W. Steroid hormone receptors selectively affect transcriptional activation but not basal repression by thyroid hormone receptors. Endocrinology 136:440-445 (1995) https://doi.org/10.1210/en.136.2.440
  20. Lee, J. W., Choi, H. S., Gyuris, J., Brent, R. & Moore, D. D. Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor. Mol Endocrinol 9:243-254 (1995) https://doi.org/10.1210/me.9.2.243
  21. Queiroz, M. S., Shao, Y. & Ismail-Beigi, F. Effect of thyroid hormone on uncoupling protein-3 mrna expression in rat heart and skeletal muscle. Thyroid 14: 177-185 (2004) https://doi.org/10.1089/105072504773297849
  22. de Lange, P. et al. Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone. Endocrinology 142:3414-3420 (2001) https://doi.org/10.1210/en.142.8.3414
  23. Knudsen, N. et al. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab 90:4019-4024 (2005) https://doi.org/10.1210/jc.2004-2225
  24. de Jesus, L. A. et al. The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. J Clin Invest 108:1379-1385 (2001) https://doi.org/10.1172/JCI200113803
  25. Baxter, J. D. et al. Selective modulation of thyroid hormone receptor action. J Steroid Biochem Mol Biol 76:31-42 (2001) https://doi.org/10.1016/S0960-0760(01)00052-8
  26. Scanlan, T. S., Yoshihara, H. A., Nguyen, N. H. & Chiellini, G. Selective thyromimetics: Tissue-selective thyroid hormone analogs. Curr Opin Drug Discov Devel 4:614-622 (2001)
  27. Zhu, X., Zhang, S., Kan, D. & Cooper, R. Haplotype block definition and its application. Pac Symp Biocomput 2004:152-163
  28. O'Shea, P. J. & Williams, G. R. Insight into the physiological actions of thyroid hormone receptors from genetically modified mice. J Endocrinol 175:553-570 (2002) https://doi.org/10.1677/joe.0.1750553
  29. Jung, M. Y., Kim B. S., Kim, Y. J., Koh, I. S. & Chung, J. H. Assessment of relationship between Fyn-related kinase gene polymorphisms and overweight/ obesity in Korean population. Korean J Physiol Pharmacol 12:83-87 (2008) https://doi.org/10.4196/kjpp.2008.12.2.83
  30. Jung, H. Y. et al. Hapanalyzer: Minimum haplotype analysis system for association studies. Genomics & Informatics 2:107-109 (2004)