Objective: Interleukin (IL)-32, encoded by the IL-32 gene, is a crucial constituent of the autophagy pathway and is involved in the regulation of Mycobacterium tuberculosis (M.tb) infection, a major global health challenge. This study aimed to examine the potential association between IL-32 polymorphisms and susceptibility to Tuberculosis(TB), highlighting the significance of genetic factors in TB risk.
Design: Sequence analysis of IL-32 was conducted in 570 individuals diagnosed with pulmonary tuberculosis (PTB), 363 individuals diagnosed with extrapulmonary tuberculosis (EPTB), and 604 healthy controls from the Chinese Han population, representing a broad spectrum of TB manifestations. Five single nucleotide polymorphisms(SNPs) were selected for analysis based on their potential impact on IL-32 function and TB susceptibility.
Results: The study revealed that the polymorphism rs12934561 C allele exhibits a positive correlation with elevated susceptibility to PTB (P=0.003, OR (95%CI) = 1.28 (1.09-1.51)), highlighting its potential role as a biomarker for PTB risk. A noteworthy relationship was observed between the rs12934561 TT genotype and the decreased likelihood of PTB, further underscoring the complexity of IL-32's role in PTB susceptibility. Moreover, it was found that protective haplotypes for PTB are TCAAC (P=0.001, OR (95%CI) = 0.75 (0.62-0.90)) and TCGTT (P=0.002, OR (95%CI) = 0.47 (0.29-0.77)) may be present in IL-32; Conversely, the potential risk haplotypes for PTB are CCGAA (P=0.007, OR (95%CI) = 1.29 (1.07-1.55)) and TCATT (P=0.033, OR (95%CI) = 1.30 (1.02-1.66)), indicating genetic variations that increase PTB susceptibility. In contrast, neither allelic nor genotypic associations were statistically significant among EPTB cases, highlighting the distinct genetic influences on the different forms of TB.
Conclusion: In this study, we discovered that polymorphisms in IL-32 are significantly associated with increased susceptibility to pulmonary TB. This finding underscores the crucial role of genetic variation in the development of TB and provides a potential avenue for targeted interventions.
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