Genetic and functional analysis of common MRC1 exon 7 polymorphisms in leprosy susceptibility.
Genetic and functional analysis of common MRC1 exon 7 polymorphisms in leprosy susceptibility.
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DOI：
10.1007/s00439-009-0775-x
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发表时间：
2010-03
期刊：
影响因子：
5.3
通讯作者：
Schurr E
中科院分区：
文献类型：
--
作者：
Alter A;de Léséleuc L;Van Thuc N;Thai VH;Huong NT;Ba NN;Cardoso CC;Grant AV;Abel L;Moraes MO;Alcaïs A;Schurr E
在两项独立研究中，染色体区域10p13与少杆菌性麻风病有关。编码人类甘露糖受体（MR）的MRC1基因位于10p13区，该基因外显子7的非同义snp被认为是麻风病的易感性因素。我们确定G396S是396名无关的越南受试者中唯一的非同义外显子7编码多态性。该SNP在490个单纯性和90个多重性麻风家庭（704例患者）中进行了基因分型（47%为少杆菌性，53%为多杆菌性）。我们观察到G396S多态性丝氨酸等位基因在麻风本身（P = 0.036）和多菌性麻风（P = 0.034）中显著的低传播。在384例巴西麻风病例（51%为少菌性麻风，49%为多菌性麻风）和399名健康对照中，我们观察到G396S多态性的甘氨酸等位基因与麻风本身（P = 0.016）和多菌性麻风（P = 0.023）存在显著相关性。此外，我们观察到外显子7编码的氨基酸单倍型与麻风病本身（P = 0.012）和多菌性麻风病（P = 0.004）显著相关。接下来，我们测试了带有MRC1的三个外显子7单倍型的过表达MR构建物（293-MR）的HEK293细胞结合和内化卵白蛋白和zymosan这两种经典MR配体的能力。在不同的变体之间没有测量摄取的差异。此外，293-MR不能结合和内化活的麻风分枝杆菌和卡介苗。我们建议MR-M。麻风相互作用是由一种身份未知的辅助宿主分子调节的。
The chromosomal region 10p13 has been linked to paucibacillary leprosy in two independent studies. The MRC1 gene, encoding the human mannose receptor (MR), is located in the 10p13 region and non-synonymous SNPs in exon 7 of the gene have been suggested as leprosy susceptibility factors. We determined that G396S is the only non-synonymous exon 7-encoded polymorphism in 396 unrelated Vietnamese subjects. This SNP was genotyped in 490 simplex and 90 multiplex leprosy families comprising 704 patients (47% paucibacillary; 53% multibacillary). We observed significant under-transmission of the serine allele of the G396S polymorphism with leprosy per se (P = 0.036) and multibacillary leprosy (P = 0.034). In a sample of 384 Brazilian leprosy cases (51% paucibacillary; 49% multibacillary) and 399 healthy controls, we observed significant association of the glycine allele of the G396S polymorphism with leprosy per se (P = 0.016) and multibacillary leprosy (P = 0.023). In addition, we observed a significant association of exon 7 encoded amino acid haplotypes with leprosy per se (P = 0.012) and multibacillary leprosy (P = 0.004). Next, we tested HEK293 cells over-expressing MR constructs (293-MR) with three exon 7 haplotypes of MRC1 for their ability to bind and internalize ovalbumin and zymosan, two classical MR ligands. No difference in uptake was measured between the variants. In addition, 293-MR failed to bind and internalize viable Mycobacterium leprae and BCG. We propose that the MR–M. leprae interaction is modulated by an accessory host molecule of unknown identity.
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影响因子：
5.2
作者：
Horvath, S;Xu, X;Laird, NM
通讯作者：
Laird, NM
影响因子：
64.8
作者：
Mira, MT;Alcaïs, A;Schurr, E
通讯作者：
Schurr, E
DOI：
10.1101/sqb.2003.68.69
发表时间：
2003-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Fan, JB;Oliphant, A;Chee, MS
通讯作者：
Chee, MS
影响因子：
30.8
作者：
Siddiqui, MR;Meisner, S;Hill, AVS
通讯作者：
Hill, AVS
影响因子：
4.4
作者：
Nigou, J;Zelle-Rieser, C;Puzo, G
通讯作者：
Puzo, G