Thameem F, Wolford J K, Bogardus C, Prochazka M
Clinical Diabetes and Nutrition Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 4212, North 16th Street, 85016, Phoenix, AZ, USA.
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.
人类原癌基因PBX1编码一种含同源结构域的蛋白质，该蛋白质可调节多个基因的表达，包括那些参与胰岛素作用和葡萄糖代谢调节的基因。PBX1位于1q22染色体上，在皮马印第安人、白种人和一个旧秩序阿米什人群体中，该区域与2型糖尿病相关。我们研究了PBX1基因组序列，以确定可能导致皮马人易患糖尿病的多态性。PBX1由9个外显子组成，跨度约为117 kb，位于微卫星D1S1677的300 kb范围内，该微卫星标志着皮马印第安人与糖尿病易感性连锁的峰值。我们在PBX1中检测到16个单核苷酸多态性，其中一个导致第21位残基处的甘氨酸被丝氨酸取代。比较患糖尿病和未患糖尿病的皮马印第安人之间多态性的频率，未发现任何显著差异，这表明PBX1中的突变并不能解释该人群中1q与2型糖尿病的连锁关系。PBX1的基因组结构为在其他人群中针对2型糖尿病和其他代谢紊乱对该候选基因座进行类似的系统研究提供了基础。
