Abstract Context: Variation in the transcription of host genes of inflammatory cytokines may underscore variation in their production. Thus, the host-immune status plays a vital role in determining the fate of the invading bacilli. Materials and Methods: Two hundred consenting volunteers and drug-resistant tuberculosis (DR-TB) patients had their blood samples amplified for the A964G (rs153109) gene. The amplicons were digested using the Xhol enzyme for genotyping purpose. Results: Among the cases: AA (homozygous wild type; n = 33), AG (heterozygous wild type; n = 36), GG (homozygous mutant, n = 10), A (wild allele, n = 102), and T (mutant allele; n = 66); while among the healthy volunteers: AA (homozygous wild type; n = 20), AG (heterozygous wild type; n = 40), GG (homozygous mutant, n = 4) A (wild allele, n = 80), and T (mutant allele; n = 48). The Hardy Weinberg Equilibrium (HWE) assessment of the samples from the control participants was statistically significant (P = 0.015). Nevertheless, the assessment of the association between the genotypes and the phenotypes assessed revealed that the healthy volunteers had more (twice) heterozygous genotype (AG) (crude statistics: P =0.045, OR = 1.99 (1.02–3.90)) when compared to the DR-TB patients. Conclusion: Although the AG genotype of A964G (rs153109)—Interleukin 27 gene may have a protective role against the development of MTB/XPERT positive DR-TB disease, the significant HWE finding among the genotype from the samples of the healthy volunteers suggests that this current result may be a false positive finding.