The association of PBX1 polymorphisms with overweight/obesity and metabolic alterations in the Korean population

  • Ban, Ju-Yeon (Brain Korea 21 Project Center, Kyung Hee University) ;
  • Kang, Soon-Ah (Department of Fermented Food Science, Seoul University of Venture & Information) ;
  • Jung, Kyung-Hee (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Kim, Hak-Jae (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) ;
  • Yim, Sung-Vin (Brain Korea 21 Project Center, Kyung Hee University) ;
  • Choe, Bong-Keun (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Hong, Seung-Jae (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Seong, Yeon-Hee (College of Veterinary Medicine, Chungbuk National 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 : 2008.12.31


Pre-B-cell leukemia transcription factor 1 (PBX1), which is located on chromosome 1q23, was recently reported to be associated with type 2 diabetes mellitus. We examined whether single nucleotide polymorphisms (SNPs) of the PBX1 gene are associated with overweight/obesity in a Korean population. We genotyped 66 SNPs in the PBX1 gene and investigated their association with clinical phenotypes found in 214 overweight/obese subjects and 160 control subjects using the Affymetrix Targeted Genotyping chip array. Seven SNPs (g.+75l86C>T, g.+78350C>A, g.+80646C>T, g.+138004C>T, g.+185219G>A, g.+191272A>C, and g.+265317T>A) were associated with the risk of obesity in three models (codominant, dominant, and recessive) (P=0.007-0.05). Haplotype 1 (CAC) and 3 (TAC) of block 3 and haplotype 2 (GGAAT) of block 10 were also strongly associated with the risk of obesity. In the control group, subjects that had homozygote for the major allele for both g.+185219G>A and g.+191272A>C showed lower high density lipoprotein-cholesterol (HDL-C) level compared to those possessing the minor allele, suggesting that the association between the homozygote for the major allele for both g.+185219G>A and g.+191272A>C and HDL-C is attributable to the increased risk of obesity. This study suggests that the PBX1 gene is a possible risk factor in overweight/obese patients.


High-density lipoprotein-cholesterol;overweight/obesity;Pre-B-cell leukemia transcription factor 1 (PBX1);single nucleotide polymorphism (SNP)


  1. Barrett JC, Fry B, Maller J & Daly MJ (2005). Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263-265
  2. Dutta S, Gannon M, Peers B, Wright C, Bonner-Weir S & Montminy M (2001). PDX:PBX complexes are required for normal proliferation of pancreatic cells during development. Proc Natl Acad Sci USA 98:1065-1070
  3. Elbein SC, HoVman MD, Teng K, Leppert MF & Hasstedt SJ (1999). A genome-wide search for type 2 diabetes susceptibility genes in Utah Caucasians. Diabetes 48:1175-1182
  4. Hirschhorn JN & Daly MJ (2005). Genome-wide association studies for common disease and complex traits. Nat Rev Genet 6:95-108
  5. Thameem F, Wolford JK, Bogardus C & Prochazka M (2001). Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in Pima Indians. Biochim Biophys Acta 1518:215-220
  6. Kitjaroentham A, Hananantachai H, Tungtrongchitr A, Pooudong S & Tungtrongchitr R (2007). R219K polymorphism of ATP binding cassette transporter A1 related with low HDL in overweight/obese Thai males. Arch Med Res 388:34-38
  7. World Health Organization Expert Consultation (2004). Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363:157-163
  8. Xiang K, Wang Y, Zheng T, Jia W, Li J, Chen L, Shen K, Wu S, Lin X, Zhang G, Wang C, Wang S, Lu H, Fang Q, Shi Y, Zhang R, Xu J & Weng Q (2004). Genome-wide search for type 2 diabetes/ impaired glucose homeostasis susceptibility genes in the Chinese: significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24. Diabetes 53:228-234
  9. Gregoire FM, Smas CM & Sul HS (1998). Understanding adipocyte differentiation. Physiol Rev 78:783-809
  10. Loos RJ & Rankinen T (2005). Gene-diet interactions on body weight changes. J Am Diet Assoc 105:S29-S30
  11. Ng MC, So WY, Cox NJ, Lam VK, Cockram CS, Critchley JA, Bell GI & Chan JC (2004). Genome-wide scan for type 2 diabetes loci in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25. Diabetes 53:1609-1613
  12. Sagerstrom CG (2004). PbX marks the spot. Dev Cell 6:737-738
  13. Sole X, Guino E, Valls J, Iniesta R & Moreno V (2006). SNPStats: a web tool for the analysis of association studies. Bioinformatics 22:1928-1929
  14. Chien KL, Chen MF, Hsu HC, Su TC, Chang WT, Lee CM & Lee YT (2008). Genetic association study of APOA1/C3/A4/A5 gene cluster and haplotypes on triglyceride and HDL cholesterol in a community-based population. Clin Chim Acta 388:78-83
  15. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ & Altshuler D (2002). The structure of haplotype blocks in the human genome. Science 296:2225-2229
  16. McCarthy MI (2003). Growing evidence for diabetes susceptibility genes from genome scan data. Curr Diab Rep 3:159-167
  17. Kim SK, Selleri L, Lee JS, Zhang AY, Gu X, Jacobs Y & Cleary ML (2002). Pbx1 inactivation disrupts pancreas development and in Ipf1-deWcient mice promotes diabetes mellitus. Nat Genet 30:430-435
  18. Kamps MP, Murre C, Sun X & Baltimore D (1990). A new homeobox gene contributes the DNA binding domain of the t (1;19) translocation protein in pre-B ALL. Cell 60:547-555
  19. Bland JM & Altman DG (1995). Multiple significance tests: the Bonferroni method. BMJ 310:170
  20. Nourse J, Mellentin JD, Galili N, Wilkinson J, Stanbridge E, Smith SD & Cleary ML (1990). Chromosomal translocation t (1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell 60:535-545
  21. Wang H, Chu W, Wang X, Zhang Z & Elbein SC (2005). Evaluation of sequence variants in the pre-B cell leukemia transcription factor 1 gene: a positional and functional candidate for type 2 diabetes and impaired insulin secretion. Mol Genet Metab 86:384-391
  22. Loos RJ & Bouchard C (2003). Obesity-is it a genetic disorder? J Intern Med 254:401-425
  23. Kadowaki T, Hara K, Yamauchi T, Terauchi Y, Tobe K & Nagai R (2003). Molecular mechanism of insulin resistance and obesity. Exp Biol Med (Maywood) 228:1111-1117
  24. Park JM, Lee EJ, Ramakrishna S, Cha DH & Baek KH (2008). Association study for single nucleotide polymorphisms in the CYP17A1 gene and polycystic ovary syndrome. Int J Mol Med 22:249-254
  25. Purcell S, Cherny SS & Sham PC (2003). Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19:149-150
  26. Ast G (2004). How did alternative splicing evolve? Nat Rev Genet 5:773-782