National Centre of Applied Human Genetics, School of life Sciences, Jawaharlal Nehru University, New Delhi 110067, India; Department of Anthropology (C.A.S), Utkal University, Vani Vihar, Bhubaneswar 751004, Odisha, India.
National Centre of Applied Human Genetics, School of life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Tuberculosis (Edinb). 2014 Jan;94(1):81-6. doi: 10.1016/j.tube.2013.10.004. Epub 2013 Oct 29.
A penta-nucleotide microsatellite marker (CCTTT)n, in NOS2A promoter region has been associated with a variety of infectious diseases, including Tuberculosis. Most of these studies, however, are limited in justifying the association to tuberculosis through independent functional assays. The present study on 915 individuals from three geographically distinct populations of India focused on the association and function simultaneously. PCR-Polyacrylamide Gel Electrophoresis and direct sequencing revealed the association of (CCTTT)10 allele with protection against Tuberculosis in all the three populations (i) independently: Odisha [p = 0.0025, pc = 0.025, OR (95%CI) = 0.5 (0.39-0.82)], Chhattisgarh-tribe [p = 0.0001, pc = 0.001, OR (95%CI) = 0.3 (0.19-0.60)] and Sahariya tribe [p = 0.02, pc = 0.2, OR (95%CI) = 0.27 (0.08-0.84)]; and (ii) together: [p < 0.0001, pc < 0.001, OR (95%CI) = 0.47 (0.35-0.63)]. In-vitro dual luciferase reporter assay revealed that (CCTTT)n microsatellite affected the expression of the reporter gene without enhancing the promoter strength in repeat-size specific manner. Thus the genetic association observed did not correlate exactly with the expression pattern and probably depended on flanking promoter SNPs (rs2779249 & rs140293907) not in strong LD with the microsatellite, and this effect needs future confirmation.
一个五核苷酸微卫星标记（CCTTT）n，位于 NOS2A 启动子区域，与多种传染病有关，包括结核病。然而，这些研究大多仅限于通过独立的功能测定来证明与结核病的相关性。本研究在印度三个地理位置不同的人群中对 915 人进行了研究，同时关注关联和功能。PCR-聚丙烯酰胺凝胶电泳和直接测序显示，（CCTTT）10 等位基因与三种人群中的结核病保护作用相关：（i）独立相关：奥里萨邦[p=0.0025，pc=0.025，OR（95%CI）=0.5（0.39-0.82）]、恰蒂斯加尔邦部落[p=0.0001，pc=0.001，OR（95%CI）=0.3（0.19-0.60）]和萨哈里亚部落[p=0.02，pc=0.2，OR（95%CI）=0.27（0.08-0.84）]；（ii）共同相关：[p<0.0001，pc<0.001，OR（95%CI）=0.47（0.35-0.63）]。体外双荧光素酶报告基因检测显示，（CCTTT）n 微卫星以重复大小特异性的方式影响报告基因的表达，而不增强启动子强度。因此，观察到的遗传关联并不完全与表达模式相关，可能取决于侧翼启动子 SNPs（rs2779249 和 rs140293907），这些 SNP 与微卫星不处于强连锁不平衡状态，这种效应需要进一步确认。
