Dubey Amit, Biswas Sanjay Kumar, Sinha Ekata, Chakma Joy Kumar, Kamal Raj, Arora Mamta, Sagar Harish, Natarajan Mohan, Bhagyawant Sameer S, Mohanty Keshar Kunja
Immunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India.
Clinical Division National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra 282004, India.
Infect Genet Evol. 2017 Jul;51:67-73. doi: 10.1016/j.meegid.2017.03.015. Epub 2017 Mar 16.
The pathogen Mycobacterium leprae causes leprosy that affects mainly skin and nerves. Polymorphisms of certain genes are substantiated to be associated with the susceptibility/resistance to leprosy. The present investigation addressed the association of Nitric Oxide Synthase2 gene polymorphisms and leprosy in a population from northern part of India. A total of 323 leprosy cases and 288 healthy controls were genotyped for four NOS2 promoter variants (rs1800482, rs2779249, rs8078340 and rs2301369) using FRET technology in Real Time PCR. None of these SNPs in promoter sites was associated with susceptibility/resistance to leprosy. NOS2 rs1800482 was found to be monomorphic with GG genotype. However, NOS2-1026T allele was observed to be in higher frequency with leprosy cases (BL and LL) who were not suffering from any reactional episodes compared to cases with ENL reaction {OR=0.30, 95% CI (0.10-0.86), p=0.024}. NOS2-1026GT genotype was more prevalent in cases without reaction (BT, BB and BL) compared to RR reactional patients {OR=0.38, 95% CI (0.17-0.86), p=0.02}. Although haplotype analysis revealed that no haplotype was associated with leprosy susceptibility/resistance with statistical significance, GTG haplotype was noted to be more frequent in healthy controls. These SNPs are observed to be in linkage disequilibrium. Although, these SNPs are not likely to influence leprosy vulnerability, -1026G>T SNP was indicated to have noteworthy role in leprosy reactions.
病原体麻风分枝杆菌会引发主要影响皮肤和神经的麻风病。某些基因的多态性已被证实与麻风病的易感性/抗性相关。本研究探讨了一氧化氮合酶2基因多态性与印度北部人群中麻风病的关联。使用实时荧光定量PCR中的荧光共振能量转移技术，对323例麻风病患者和288名健康对照者进行了4种NOS2启动子变体（rs1800482、rs2779249、rs8078340和rs2301369）的基因分型。启动子位点的这些单核苷酸多态性均与麻风病的易感性/抗性无关。发现NOS2 rs1800482呈GG基因型单态性。然而，与有结节性红斑反应的患者相比，在未发生任何反应性发作的麻风病患者（瘤型和界线类偏瘤型）中，观察到NOS2 -1026T等位基因频率更高{比值比=0.30，95%可信区间（0.10 - 0.86），p = 0.024}。与有逆行性反应的患者相比，NOS2 -1026GT基因型在无反应的患者（未定类、偏结核样型和瘤型）中更为普遍{比值比=0.38，95%可信区间（0.17 - 0.86），p = 0.02}。尽管单倍型分析显示没有单倍型与麻风病易感性/抗性具有统计学意义的关联，但注意到GTG单倍型在健康对照者中更为常见。观察到这些单核苷酸多态性处于连锁不平衡状态。虽然这些单核苷酸多态性不太可能影响麻风病易感性，但 -1026G>T单核苷酸多态性在麻风病反应中显示出重要作用。
