The association of PBX1 polymorphisms with overweight/obesity and metabolic alterations in the Korean population
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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.+75186C>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.
Abstract
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.+75186C>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.
참고문헌 (26)
- Ast G, "How did alternative splicing evolve?", Nat Rev Genet, 5, pp.773~782 (2004)
- Barrett JC, "Haploview: analysis and visualization of LD and haplotype maps", Bioinformatics, 21, pp.263~265 (2005)
- Bland JM, "Multiple significance tests: the Bonferroni method", BMJ, 310, pp.170~ (1995)
- Chien KL, "Genetic association study of APOA1", C3, A5 gene cluster and haplotypes on triglyceride and HDL cholesterol in a community-based population, pp.Clin Chim Acta, 2008[DOI]
- Dutta S, "PDX:PBX complexes are required for normal proliferation of pancreatic cells during development", Proc Natl Acad Sci USA, 98, pp.1065~1070 (2001)
- Elbein SC, "A genome-wide search for type 2 diabetes susceptibility genes in Utah Caucasians", Diabetes, 48, pp.1175~1182 (1999)
- Gabriel SB, "The structure of haplotype blocks in the human genome", Science, 296, pp.2225~2229 (2002)
- Gregoire FM, "Understanding adipocyte differentiation", Physiol Rev, 78, pp.783~809 (1998)
- Hirschhorn JN, "Genome-wide association studies for common disease and complex traits", Nat Rev Genet, 6, pp.95~108 (2005)
- Kadowaki T, "Molecular mechanism of insulin resistance and obesity", Exp Biol Med (Maywood), 228, pp.1111~1117 (2003)
- Kamps MP, "A new homeobox gene contributes the DNA binding domain of the t (1;19) translocation protein in pre-B ALL", Cell, 60, pp.547~555 (1990)
- Kitjaroentham A, "R219K polymorphism of ATP binding cassette transporter A1 related with low HDL in overweight", obese Thai males, 2007, pp.388, 34~38
- Kim SK, "Pbx1 inactivation disrupts pancreas development and in Ipf1-deWcient mice promotes diabetes mellitus", Nat Genet, 30, pp.430~435 (2002)
- Loos RJ, "Obesity-is it a genetic disorder?", J Intern Med, 254, pp.401~425 (2005)
- Loos RJ, "Gene-diet interactions on body weight changes", J Am Diet Assoc, 105, pp.S29~S30 (2005)
- McCarthy MI, "Growing evidence for diabetes susceptibility genes from genome scan data", Curr Diab Rep, 3, pp.159~167 (2003)
- Ng MC, "Genome-wide scan for type 2 diabetes loci in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25", Diabetes, 53, pp.1609~1613 (2004)
- Nourse J, "Chromosomal translocation t (1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor", Cell, 60, pp.535~545 (1990)
- Park J, "Association study for single nucleotide polymorphisms in the CYP17A1 gene and polycystic ovary syndrome", Int J Mol Med, 22, pp.249~254 (2008)
- Purcell S, "Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits", Bioinformatics, 19, pp.149~150 (2003)
- Sagerstrom CG, "PbX marks the spot", Dev Cell, 6, pp.737~738 (2004)
- Sole X, "SNPStats: a web tool for the analysis of association studies", Bioinformatics, 22, pp.1928~1929 (2006)
- Thameem F, "Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in Pima Indians", Biochim Biophys Acta, 1518, pp.215~220 (2001)
- Wang H, "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, pp.384~391 (2005)
- World Health Organization Expert Consultation, "Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies", Lancet, 363, pp.157~163 (2004)
- Xiang K, "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, 2004, pp.53, 228~234