性别特异性与对鸟分枝杆菌复合体肺病易感性和细胞程序性死亡 1 基因多态性相关。

Sex-Specific Associations Between Susceptibility to Mycobacterium avium Complex Lung Disease and Programmed Cell Death 1 Gene Polymorphisms.

机构信息

Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

出版信息

J Infect Dis. 2023 Jun 28;228(1):18-27. doi: 10.1093/infdis/jiac396.

DOI:10.1093/infdis/jiac396

PMID:36161323

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

PDCD1 genetic polymorphisms were associated with the risk of MAC-LD in a sex-specific pattern, possibly through regulation of PD-1 expression.

摘要

背景

鸟分枝杆菌复合群肺病（MAC-LD）优先发生在绝经后妇女中，并且可能涉及程序性细胞死亡 1（PD-1）途径的免疫衰竭。目前尚不清楚 MAC-LD 的易感性与程序性死亡 1 基因（PDCD1）多态性之间是否存在特定于性别的关联。

方法

在台湾的 2 家医疗中心纳入了 152 例 MAC-LD 患者和 167 例对照者。对 PDCD1 基因中的 5 个单核苷酸多态性进行了基因分型，并分析了它们与 MAC-LD 和可溶性 PD-1 蛋白的关系，特别是在性别亚组中。

结果

PDCD1 rs2227982 多态性与女性 MAC-LD 风险增加相关（AA 对 AG 对 GG 的调整后的优势比，2.205 [95%置信区间，1.108-4.389]；P =.02），而 rs10204525 TT 基因型与男性的低风险相关（TT 对 TC 和 CC，0.396 [.176-.890]；P =.02）。与 rs10204525 TT 的男性相比，rs2227982 AG 和 AA 的女性风险分别增加了 2.7 倍和 5.0 倍。rs2227982 AG 和 AA 的女性亚组的可溶性 PD-1 水平低于其余女性（中位数水平[四分位间距]，46.7 [33.7-71.5] pg/mL 比 66.2 [48.6-101.5] pg/mL；P <.001）。