ABC TRANSPORTERS IN HUMAN DISEASE AND DRUG RESISTANCE

ATP结合盒（ABC）基因家族编码一组不同的 这些转运蛋白将多种化合物泵入细胞， 细胞和组织的膜。人类ABC基因参与了许多 疾病，包括囊性纤维化，肾上腺脑白质营养不良， 家族性持续性高胰岛素血症性低血糖。肿瘤耐药性 多药耐药（multidrug resistance，MDR）是目前 癌症化疗在某些肿瘤中，MDR与 P-糖蛋白/（PGP）MDR和多药耐药的过度表达- MRP相关蛋白基因。PGP和MRP是ABC家族转运蛋白。 我们以前已经确定了超过21个新的人类ABC基因。遗传 这些基因的位置以及它们的表达模式 确定了这些基因之一，ABCR，只表达于 视网膜将该基因定位于染色体1 p13 - 21， Stargardt黄斑营养不良（STGD 1）基因，一种隐性疾病 导致儿童视力下降。我们一共发现了19个不同的 STGD 1患者中ABCR基因的突变，包括几个框- 移位和无义等位基因。STGD 1与年龄表型相似- 相关性黄斑变性（AMD），一种常见的视网膜病变形式， 发生在65岁以上的人身上的退化。我们研究了一组 167例AMD患者，发现其中16%的人在ABCR中有突变， 基因了解该基因突变在STGD 1和AMD中的作用， 识别ABCR的正常功能应该有助于阐明 黄斑变性的发展。对其他人的进一步定性 ABC基因可能提供其他人类疾病和肿瘤的信息。

The ATP-binding cassette (ABC) gene family encodes a diverse group of transporter proteins that pump a wide variety of compounds across the membranes of cells and tissues. Human ABC genes are involved in a number of diseases, including cystic fibrosis, adrenoleuko-dystrophy, and familial persistent hyperinsulinemic hypoglycemia. Resistance of tumors to multiple drugs (multidrug resistance, MDR) is a major limitation of cancer chemotherapy. MDR is associated in certain tumors with the overexpression of the P-glycoprotein/(PGP)MDR and multidrug resistance- related protein (MRP) genes. PGP and MRP are ABC family transporters. We have previously identified over 21 new human ABC genes. The genetic location of each of these genes as well as their expression pattern has been determined. One of these genes, ABCR, is expressed exclusively in the retina. The gene was mapped to chromosome 1p13- 21, the location of the Stargardt macular dystrophy (STGD1) gene, a recessive disorder causing vision loss in children. We identified a total of 19 different mutations in the ABCR gene in STGD1 patients, including several frame- shift and non-sense alleles. STGD1 is phenotypically similar to age- related macular degeneration (AMD), a common form of retinal degeneration that occurs in people over age 65. We examined a cohort of 167 AMD patients and found that 16% of them had mutations in the ABCR gene. Understanding the role of mutations in this gene in STGD1 and AMD, and identifying the normal function of ABCR should shed light on the development of macular degeneration. Further characterization of other ABC genes may provide information on other human diseases and neoplasms.