Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, New Delhi 110007, India.
Hum Immunol. 2011 Jul;72(7):576-80. doi: 10.1016/j.humimm.2011.03.014. Epub 2011 Apr 20.
Ethnic specificity is a key determinant in understanding the association of genetic variants with outcome of disease susceptibility. SP110, a component of the nuclear body, has been subjected to association studies with conflicting results. In this study we probed SP110 variants in pulmonary (PTB) and lymph node tuberculosis (LNTB) cases to explore their role in controlling susceptibility to Mycobacterium tuberculosis infection in north Indians. We genotyped 24 SP110 variants in over 140 north Indian tuberculosis cases and 78 ethnicity-matched controls. The SP110 gene variants were available from public databases. The cases and controls were free of any population stratification when subjected to Eigenstrat principal component analysis. Genotyping was carried out using the Sequenom MassARRAY platform. Applying exclusion criteria, 11 single nucleotide polymorphisms (SNPs) of the LNTB panel and 13 SNPs of the PTB panel passed all filters and were analyzed further. No significant association was observed between SP110 variants and PTB. Surprisingly, we discovered evidence of an association of SP110 variants with LNTB, a form of extrapulmonary tuberculosis, at 3 loci, namely, rs6436915, rs1427294, and rs1346311. When permutations analysis (n = 10,000) of allelic p values was undertaken, only rs1427294 passed the test with its p value remaining statistically significant. The C allele of rs1427294 exhibited a 5-fold risk of developing LNTB. No significant haplotypes were observed. In the pilot study presented here, our results provide evidence for the first time that SP110 may be a risk determinant locus in LNTB while confirming a doubtful role of SP110 in PTB in north Indians. In general, the results might indicate a role of SP110 variants in extrapulmonary tuberculosis rather than PTB.
种族特异性是理解遗传变异与疾病易感性之间关联的关键决定因素。核体的组成部分 SP110 已进行了关联研究，但结果相互矛盾。在这项研究中，我们研究了印度北部人群的 SP110 变体，以探讨其在控制结核分枝杆菌感染易感性中的作用。我们对超过 140 例印度北部肺结核病例和 78 例种族匹配的对照进行了 24 种 SP110 变体的基因分型。SP110 基因变体可从公共数据库中获得。在进行 Eigenstrat 主成分分析时，病例和对照均无任何群体分层。基因分型使用 Sequenom MassARRAY 平台进行。应用排除标准，LNTB 面板的 11 个单核苷酸多态性（SNP）和 PTB 面板的 13 个 SNP 通过了所有筛选，并进一步进行了分析。未观察到 SP110 变体与 PTB 之间存在显著关联。令人惊讶的是，我们发现 SP110 变体与 LNTB（一种肺外结核病）之间存在关联的证据，在 3 个位点，即 rs6436915、rs1427294 和 rs1346311，均有发现。当进行等位基因 p 值的置换分析（n = 10,000）时，只有 rs1427294 通过了测试，其 p 值仍具有统计学意义。rs1427294 的 C 等位基因使发生 LNTB 的风险增加了 5 倍。未观察到显著的单倍型。在本研究中，我们的结果首次提供了证据，表明 SP110 可能是 LNTB 的风险决定因素，同时证实了 SP110 在印度北部人群中对 PTB 的作用存在疑问。总的来说，这些结果可能表明 SP110 变体在肺外结核病而非 PTB 中起作用。
