Polymorphisms in human NRF2 is associated with susceptibility to tuberculosis

Introduction: Tuberculosis (TB) associated with oxidative stress remains to be a major global public health. Nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2, encoded by NRF2 ), a mastertranscriptional activator of antioxidant and detoxifying genes, plays a critical role in the regulation of cellular redox status. There has been no report on the relativity of NRF2 polymorphisms and tuberculosis susceptibility. Objective: This study aimed to investigate association of NRF2 single nucleotide polymorphisms (SNPs), rs10497511, rs13005431, rs1962142, rs2364723 and rs6726395 with susceptibility to tuberculosis. Methods: Blood samples were obtained from 636 tuberculosis patients (324 males and 312 females) with mean age of 36.77±15.712 years, and 608 healthy controls (302 males and 306 females) with mean age of 37.14±15.678 years. Genotyping was performed using polymerase chain reaction with MassArray Analyzer 4 system Results: The rs13005431 C allele demonstrated an increased risk of developing tuberculosis (p = 0.01, OR (95%CI) = 1.34(1.07–1.68)), and the rs2364723 C allele was protective against tuberculosis compared to healthy controls (p = 0.028, OR (95%CI) =0.84(0.72–0.98)). The rs6726395 G allele was an other protective factor only in females subgroup (p = 0.002, OR (95%CI) =0.70(0.55-0.88)). The haplotype analysis showed one potential risk haplotype, AGACG in NRF2 (p = 0.015, OR (95%CI) = 1.34(1.06-1.69)). The GGATC haplotype was significantly protective for tuberculosis only in females subgroup (p = 0.004, OR (95%CI) = 0.72 (0.57-0.90)). Conclusion: Our results suggest that NRF2 polymorphisms are associated with susceptibility to tuberculosis.