Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in Pima Indians

Biochim Biophys Acta. 2001 Mar 19;1518(1-2):215-20. doi: 10.1016/s0167-4781(01)00189-0.


The human proto-oncogene PBX1 codes for a homeodomain containing protein that modulates expression of several genes, including those contributing to regulation of insulin action and glucose metabolism. PBX1 is located on chromosome 1q22, a region linked with type 2 diabetes in Pima Indians, Caucasians, and an Old Order Amish population. We have investigated the PBX1 genomic sequence to identify polymorphisms that may contribute to diabetes susceptibility in the Pimas. PBX1 is composed of nine exons spanning approx. 117 kb and is located within 300 kb of microsatellite D1S1677, which marks the peak of linkage to diabetes susceptibility in the Pima Indians. We detected 16 single nucleotide polymorphisms in PBX1 including one causing a glycine to serine substitution at residue 21. Comparison of the frequencies of the polymorphisms between affected and unaffected Pima Indians did not detect any significant differences, indicating that mutations in PBX1 do not explain the linkage of 1q with type 2 diabetes in this population. The genomic structure of PBX1 provides a basis for similar systematic examinations of this candidate locus in other populations in relation to both type 2 diabetes and other metabolic disorders.

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • DNA, Complementary
  • DNA-Binding Proteins / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Exons
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation
  • Humans
  • Indians, North American / genetics*
  • Introns
  • Molecular Sequence Data
  • Polymorphism, Genetic*
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics*
  • Tissue Distribution
  • United States


  • 3' Untranslated Regions
  • DNA, Complementary
  • DNA-Binding Proteins
  • MAS1 protein, human
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • pbx1 protein, human

Associated data

  • GENBANK/AB313396
  • GENBANK/AB313397
  • GENBANK/AB313398
  • GENBANK/AB313399
  • GENBANK/AB313400
  • GENBANK/AB313401
  • GENBANK/AB313402
  • GENBANK/AB313403
  • GENBANK/AB313404