Susceptibility to leprosy is associated with PARK2 and PACRG
Susceptibility to leprosy is associated with PARK2 and PACRG
复制标题
DOI：
10.1038/nature02326
复制
发表时间：
2004-02-12
期刊：
影响因子：
64.8
通讯作者：
Schurr, E
中科院分区：
文献类型：
--
作者：
Mira, MT;Alcaïs, A;Schurr, E
麻风病是由麻风分枝杆菌引起的，每年影响约70万人（1）。长期以来，人们一直认为麻风病具有很强的遗传成分（2），最近我们将麻风病易感基因定位于6号染色体区域q25-q26（参考文献3）。在这里，我们调查这一地区进一步使用系统的关联扫描的染色体间隔最有可能窝藏这个麻风病易感基因座。在197个越南家庭中，我们发现麻风病与位于一个大约100平方米的街区的17个标记物之间存在显著关联。与帕金森病基因PARK 2和共调节基因PACRG共享的5'调控区重叠的80个酶。在17个危险等位基因中，只有两个等位基因对麻风病具有高度预测性。这在来自巴西的975例无关麻风病例和对照样本中得到证实，其中相同的等位基因与麻风密切相关。因此，PARK 2和PACRG共有的调控区变异是麻风病的共同危险因素。
Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year(1). It has long been thought that leprosy has a strong genetic component(2), and recently we mapped a leprosy susceptibility locus to chromosome 6 region q25-q26 (ref. 3). Here we investigate this region further by using a systematic association scan of the chromosomal interval most likely to harbour this leprosy susceptibility locus. In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80 kilobases overlapping the 5' regulatory region shared by the Parkinson's disease gene PARK2 and the co-regulated gene PACRG. Possession of as few as two of the 17 risk alleles was highly predictive of leprosy. This was confirmed in a sample of 975 unrelated leprosy cases and controls from Brazil in whom the same alleles were strongly associated with leprosy. Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy.