Analyses of the NRAMP1 and IFN-gammaR1 genes in women with Mycobacterium avium-intracellulare pulmonary disease.
Analyses of the NRAMP1 and IFN-gammaR1 genes in women with Mycobacterium avium-intracellulare pulmonary disease.
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患有鸟分枝杆菌细胞内肺病的女性的 NRAMP1 和 IFN-gammaR1 基因分析。
DOI：
10.1164/ajrccm.157.2.9706012
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Kao,PN
中科院分区：
文献类型：
--
作者：
Huang,JH;Oefner,PJ;Adi,V;Ratnam,K;Ruoss,SJ;Trako,E;Kao,PN
鸟细胞内分枝杆菌（MAI）肺病在无肺部疾病的HIV阴性老年女性人群中引起大量发病。这些患者的疾病易感性的原因尚不清楚，尽管他们的相对表型同质性表明存在一种常见的、微妙的免疫缺陷。进行了一项调查，以确定这些患者的天然耐药相关巨噬细胞蛋白（NRAMP 1）或干扰素γ受体1（IFN- γ R1）基因是否存在缺陷。一个常染色体隐性基因murinenramp的点突变控制对细胞内微生物的抗性，与小鼠中的牛分枝杆菌感染相关。分析人类NRAMP 1相应区域、两个编码多态性和一个启动子NRAMP 1多态性，以及两个IFN- γ R1多态性，以确定是否存在与疾病相关的等位基因。从8名患有MAI肺病的妇女和4名对照中纯化基因组DNA。通过PCR扩增感兴趣的区域;通过限制性片段长度多态性分析三个位点，并且使用变性高效液相色谱法分析三个位点。另外18个随机对照的NRAMP 1启动子多态性通过微卫星大小分析。在NRAMP 1中未发现与小鼠突变相对应的等位基因，也未发现两个编码区的等位基因。在NRAMP 1启动子微卫星中，8例患者中有3例为二核苷酸序列插入杂合子，22例对照中有10例为杂合子。所有患者均未出现两种已知的IFN- γ R1突变。总之，在患有MAI肺病的女性中，没有证据表明NRAMP 1或IFN- γ R1的遗传缺陷与疾病相关。
Mycobacterium avium-intracellulare(MAI) pulmonary disease causes substantial morbidity in a population of older, HIV-negative women without preexisting lung disease. The cause for disease susceptibility in these patients is unknown, although their relative phenotypic homogeneity suggests the existence of a common, subtle immune deficiency. An investigation was undertaken to determine if these patients have a defect in their natural resistance-associated macrophage protein (NRAMP1) or interferon γ receptor 1 (IFN- γ R1) genes. A point mutation in murinenramp, an autosomal recessive gene controlling resistance to intracellular organisms, correlates with overwhelmingMycobacterium bovisinfection in mice. The corresponding region in humanNRAMP1, two coding polymorphisms and one promoterNRAMP1polymorphism, as well as twoIFN- γ R1polymorphisms, were analyzed to determine if an allele was present to correlate with disease. Genomic DNA was purified from eight women with MAI pulmonary disease and four controls. Regions of interest were amplified by PCR; three sites were analyzed by restriction fragment length polymorphisms, and three were analyzed using denaturing high-performance liquid chromatography. TheNRAMP1promoter polymorphism of 18 additional random controls was analyzed by microsatellite sizing. No allelism was found inNRAMP1corresponding to the murine mutation, or in the two coding regions. In theNRAMP1promoter microsatellite, 3 of 8 patients were heterozygous for a dinucleotide sequence insertion, as were 10 of 22 controls. None of the patients had either of the two knownIFN- γ R1mutations. In conclusion, in women with MAI pulmonary disease, there is no evidence for a genetic defect inNRAMP1orIFN- γ R1to correlate with disease.