The relationship between IRGM polymorphism and pneumoconiosis susceptibility_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

WANG Yun ¹ , YUAN Leyong ² , WANG Meifang ¹ , MENG Zhongji ³ , DUAN Jingzhu ¹ ,  DU Shiming ⁴ ,  TANG Yijun ¹

1. Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P. R. China;
2. Department of Immunology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P. R. China;
3. Institute of Biomedical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P. R. China;
4. Department of Scientific Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P. R. China;

Corresponding?author：

DU Shiming, Email: dsmch@sina.com; TANG Yijun, Email: tangyijun_799@163.com

Keywords：

Pneumoconiosis; Susceptibility; Immunity related GTPase M; Polymorphism

DOI：

10.7507/1671-6205.201907029

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Objective To investigate the relationship between immunity related GTPase M gene (IRGM) polymorphism and pneumoconiosis susceptibility.Methods Two hundred and forty-eight pneumoconiosis patients were selected as a case group, 275 non-pneumoconiosis workers with similar age, sex, nationality, type of work and working age were selected as a control group. The genotypes and alleles of three single nucleotide polymorphisms (SNP) of IRGM were detected by Sanger sequencing in case group and control group. SNPstats software was used to analyze the correlation between single SNP and pneumoconiosis, and SHEsis software was used to analyze the linkage imbalance and haplotype of each locus.Results The distribution frequency of IRGM rs4958846 TT genotype in the case group was higher than that of the control group. The distribution frequency of TC and CC genotype in control group was higher than that of the case group. The distribution frequency of T allele in the case group was higher than that of the control group. The distribution frequency of C allele in the control group was higher than that of the case group. All of the differences were statistical significant (P<0.05). There was no statistical significance for the distribution difference between the two groups in terms of genotype and allele at IRGM rs4958842 and rs4958843 (P>0.05). After linkage disequilibrium analysis to three gene loci at rs4958842, rs4958843 and rs4958846 of IRGM, there was linkage disequilibrium between each other gene loci (D'>0.7, r²>0.3). Haplotype analysis was conducted on three genetic loci and established four kinds of haplotypes, the frequency distribution of ACT and ACC haplotypes had statistical significances between the two groups (P<0.05), and the other haplotype had no significant correlation with the susceptibility of pneumoconiosis (P>0.05).Conclusion T allele and ACT haplotype of IRGM rs4958846 may be associated with pneumoconiosis susceptibility.

Citation： WANG Yun, YUAN Leyong, WANG Meifang, MENG Zhongji, DUAN Jingzhu, DU Shiming, TANG Yijun. The relationship between IRGM polymorphism and pneumoconiosis susceptibility. Chinese Journal of Respiratory and Critical Care Medicine, 2020, 19(4): 366-370. doi: 10.7507/1671-6205.201907029 Copy

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14.	Rufini S, Ciccacci C, Di Fusco D, et al. Autophagy and inflammatory bowel disease: association between variants of the autophagy-related IRGM gene and susceptibility to Crohn's disease. Dig Liver Dis, 2015, 47(9): 744-750.
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1. 王慧, 胡建安. 表觀遺傳修飾在塵肺病發病中的作用研究. 中華勞動衛生職業病雜志, 2019, 37(4): 310-317.
2. 張春民. TRAIL/TRAILR 介導煤工塵肺患者肺泡巨噬細胞凋亡的機制[D]. 河北聯合大學, 2011.
3. Wang Y, Liu N, Su X, et al. Epigallocatechin-3-gallate attenuates transforming growth factor-β1 induced epithelial-mesenchymal transition via Nrf2 regulation in renal tubular epithelial cells. Biomed Pharmacother, 2015, 70: 260-267.
4. 吳芬, 夏昭林. 基因多態性與塵肺病遺傳易感性關系研究進展. 中國工業醫學雜志, 2008, 21(5): 309-311.
5. Chu M, Ji X, Chen W, et al. A genome-wide association study identifies susceptibility loci of silica-related pneumoconiosis in Han Chinese. Hum Mol Genet, 2014, 23(23): 6385-6394.
6. Sandoval H, Kodali S, Wang J. Regulation of B cell fate, survival, and function by mitochondria and autophagy. Mitochondrion, 2017, 7249(17): 30191-30195.
7. 王海杰, 譚玉珍, 何韜, 等. 塵粒對巨噬細胞自噬的影響. 中國病理生理雜志, 2008, 24(8): 1524-1528.
8. Yuan J, Han R, Esther A, et al. Polymorphisms in autophagy related genes and the coal workers' pneumoconiosis in a Chinese population. Gene, 2017, 632: 36-42.
9. Chen S, Yuan J, Yao S, et al. Lipopolysaccharides may aggravate apoptosis through accumulation of autophagosomes in alveolar macrophages of human silicosis. Autophagy, 2015, 11(12): 2346-2357.
10. Di Pietrantonio T, Schurr E. Host-pathogen specificity in tuberculosis. Adv Exp Med Biol, 2013, 783: 33-44.
11. Songane M, Kleinnijenhuis J, Netea MG, et al. The role of autophagy in host defence against Mycobacterium tuberculosis infection. Tuberculosis (Edinb), 2012, 92(5): 388-396.
12. Bahari G, Hashemi M, Taheri M, et al. Association of IRGM polymorphisms and susceptibility to pulmonary tuberculosis in Zahedan, Southeast Iran. ScientificWorldJournal, 2012, 2012: 950801.
13. Chauhan S, Mandell MA, Deretic V. Mechanism of action of the tuberculosis and Crohn disease risk factor IRGM in autophagy. Autophagy, 2016, 12(2): 429-431.
14. Rufini S, Ciccacci C, Di Fusco D, et al. Autophagy and inflammatory bowel disease: association between variants of the autophagy-related IRGM gene and susceptibility to Crohn's disease. Dig Liver Dis, 2015, 47(9): 744-750.
15. Che N, Li S, Gao T, et al. Identification of a novel IRGM promoter single nucleotide polymorphism associated with tuberculosis. Clin Chim Acta, 2010, 411(21-22): 1645-1649.

Chinese Journal of Respiratory and Critical Care Medicine

The relationship between IRGM polymorphism and pneumoconiosis susceptibility

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