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Mycobacterium avium complex lung disease (MAC-LD) preferentially occurs in postmenopausal women and may have immune exhaustion involving the programmed cell death 1 (PD-1) pathway. It is still unknown whether sex-specific associations between susceptibility to MAC-LD and programmed cell death 1 gene (PDCD1) polymorphisms exist. Adult patients with MAC-LD (n = 152) and controls (n = 167) were included at 2 medical centers in Taiwan. Five single-nucleotide polymorphisms in PDCD1 genes were genotyped, and their associations with MAC-LD and soluble PD-1 protein were analyzed, especially in sex subgroups. PDCD1 rs2227982 polymorphism was associated with increased risk of MAC-LD in women (adjusted odds ratio for AA vs AG vs GG, 2.205 [95% confidence interval, 1.108-4.389]; P = .02), and the rs10204525 TT genotype was associated with low risk in men (TT vs TC and CC, 0.396 [.176-.890]; P = .02). Compared with men with rs10204525 TT, women with rs2227982 AG and with AA had 2.7- and 5.0-fold increased risks, respectively. Soluble PD-1 levels were lower in the female subgroup with rs2227982 AG and AA than in the remainder (median level [interquartile range], 46.7 [33.7-71.5] pg/mL vs 66.2 [48.6-101.5] pg/mL; P < .001). PDCD1 genetic polymorphisms were associated with the risk of MAC-LD in a sex-specific pattern, possibly through regulation of PD-1 expression. © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail:


Sheng-Wei Pan, Jia-Yih Feng, Lawrence Shih-Hsin Wu, Chin-Chung Shu, Ping-Huai Wang, Jann-Yuan Wang, Hao-Chien Wang, Wei-Juin Su, Yuh-Min Chen, Chong-Jen Yu. Sex-Specific Associations Between Susceptibility to Mycobacterium avium Complex Lung Disease and Programmed Cell Death 1 Gene Polymorphisms. The Journal of infectious diseases. 2023 Jun 28;228(1):18-27

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PMID: 36161323

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