遗传血统对麻风病患者NFKβ1、CASP8、PAR1、IL4和CYP19A1基因插入缺失标记的影响
Influence of Genetic Ancestry on INDEL Markers of NFKβ1, CASP8, PAR1, IL4 and CYP19A1 Genes in Leprosy Patients.
作者信息
Pinto Pablo, Salgado Claudio, Santos Ney Pereira Carneiro, Santos Sidney, Ribeiro-dos-Santos Ândrea
机构信息
Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brasil; Núcleo de Pesquisas em Oncologia - NPO, Universidade Federal do Pará, Belém, Pará, Brasil.
Laboratório de Dermatoimunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brasil.
出版信息
PLoS Negl Trop Dis. 2015 Sep 14;9(9):e0004050. doi: 10.1371/journal.pntd.0004050. eCollection 2015.
BACKGROUND
Leprosy is an insidious infectious disease caused by the obligate intracellular bacteria Mycobacterium leprae, and host genetic factors can modulate the immune response and generate distinct categories of leprosy susceptibility that are also influenced by genetic ancestry.
METHODOLOGY/PRINCIPAL FINDINGS: We investigated the possible effects of CYP19A1 [rs11575899], NFKβ1 [rs28362491], IL1α [rs3783553], CASP8 [rs3834129], UGT1A1 [rs8175347], PAR1 [rs11267092], CYP2E1 [INDEL 96pb] and IL4 [rs79071878] genes in a group of 141 leprosy patients and 180 healthy individuals. The INDELs were typed by PCR Multiplex in ABI PRISM 3130 and analyzed with GeneMapper ID v3.2. The NFKβ1, CASP8, PAR1 and IL4 INDELs were associated with leprosy susceptibility, while NFKβ1, CASP8, PAR1 and CYP19A1 were associated with the MB (Multibacilary) clinical form of leprosy.
CONCLUSIONS/SIGNIFICANCE: NFKβ1 [rs28362491], CASP8 [rs3834129], PAR1 [rs11267092] and IL4 [rs79071878] genes are potential markers for susceptibility to leprosy development, while the INDELs in NFKβ1, CASP8, PAR1 and CYP19A1 (rs11575899) are potential markers for the severe clinical form MB. Moreover, all of these markers are influenced by genetic ancestry, and European contribution increases the risk to leprosy development, in other hand an increase in African contribution generates protection against leprosy.
背景
麻风病是一种由专性细胞内细菌麻风分枝杆菌引起的隐匿性传染病，宿主遗传因素可调节免疫反应，并产生不同类别的麻风易感性，这也受遗传血统的影响。
方法/主要发现：我们在一组141例麻风病患者和180名健康个体中研究了CYP19A1 [rs11575899]、NFKβ1 [rs28362491]、IL1α [rs3783553]、CASP8 [rs3834129]、UGT1A1 [rs8175347]、PAR1 [rs11267092]、CYP2E1 [INDEL 96pb]和IL4 [rs79071878]基因的可能影响。通过在ABI PRISM 3130中进行PCR多重分析对插入缺失进行分型，并用GeneMapper ID v3.2进行分析。NFKβ1、CASP8、PAR1和IL4的插入缺失与麻风易感性相关，而NFKβ1、CASP8、PAR1和CYP19A1与麻风的MB（多菌型）临床类型相关。
结论/意义：NFKβ1 [rs28362491]、CASP8 [rs3834129]、PAR1 [rs11267092]和IL4 [rs79071878]基因是麻风病发生易感性的潜在标志物，而NFKβ1、CASP8、PAR1和CYP19A1（rs11575899）中的插入缺失是严重临床类型MB的潜在标志物。此外，所有这些标志物都受遗传血统的影响，欧洲血统的贡献增加了患麻风病的风险，另一方面，非洲血统贡献的增加则产生对麻风病的保护作用。
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