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Polymorphisms in Autophagy-Related Gene IRGM Are Associated with Susceptibility to Autoimmune Thyroid Diseases.

ABSTRACT: Background:To date, studies have shown that polymorphisms in an autophagy-related gene, IRGM, are linked with different diseases, especially autoimmune diseases. The present study aimed to examine the roles of IRGM polymorphisms in autoimmune thyroid diseases (AITD). Methods:Three polymorphisms in IRGM gene (rs10065172, rs4958847, and rs13361189) were genotyped in 1569 participants (488 with Graves' disease, 292 with Hashimoto's thyroiditis, and 789 healthy controls) using PCR-based ligase detection reaction method. Gene-disease associations were evaluated for the three SNPs. Results:T allele of rs10065172, A allele of rs4958847, and C allele of rs13361189 were all higher in Graves' disease patients than controls, and the ORs were OR = 1.207 (P = 0.022), OR = 1.207 (P = 0.027), and OR = 1.200 (P = 0.027), respectively. After adjusting for sex and age, rs10065172 and rs13361189 were still associated with GD under both the allele model and dominant model, and the adjusted ORs for rs10065172 were 1.20 (P = 0.033) and 1.33 (P = 0.024), while the adjusted ORs for rs13361189 were 1.19 (P = 0.042) and 1.33 (P = 0.026), respectively. No significant difference was found between Hashimoto's thyroiditis patients and controls. Haplotype analysis found that CTA frequency was distinguishingly higher in Graves' disease patients (OR = 1.195, P = 0.030). The frequency of TCG haplotype was distinguishingly lower in AITD and Graves' disease patients (OR = 0.861, P = 0.044; OR = 0.816, P = 0.017). Conclusions:Our study reveals IRGM as a susceptibility gene of AITD and Graves' disease for the first time.

SUBMITTER: Yao QM

PROVIDER: S-EPMC6016217 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Polymorphisms in Autophagy-Related Gene <i>IRGM</i> Are Associated with Susceptibility to Autoimmune Thyroid Diseases.

Yao Qiu-Ming QM Zhu Yuan-Feng YF Wang Wen W Song Zhen-Yu ZY Shao Xiao-Qing XQ Li Ling L Song Rong-Hua RH An Xiao-Fei XF Qin Qiu Q Li Qian Q Zhang Jin-An JA

BioMed research international 20180611

<h4>Background</h4>To date, studies have shown that polymorphisms in an autophagy-related gene, <i>IRGM</i>, are linked with different diseases, especially autoimmune diseases. The present study aimed to examine the roles of <i>IRGM</i> polymorphisms in autoimmune thyroid diseases (AITD).<h4>Methods</h4>Three polymorphisms in <i>IRGM</i> gene (rs10065172, rs4958847, and rs13361189) were genotyped in 1569 participants (488 with Graves' disease, 292 with Hashimoto's thyroiditis, and 789 healthy co ...[more]

PMID: 29992164

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Project description:ObjectiveAutophagy is the regulated catabolic process for recycling damaged or unnecessary organelles, which plays crucial roles in cell survival during nutrient deficiency, and innate immune defense against pathogenic microorganisms. Autophagy has been also reported to be involved in various conditions including inflammatory diseases. IRGM (human immunity-related GTPase) has an important function in eliminating Mycobacterium tuberculosis from host cells via autophagy. We examined the association between genetic polymorphism and clinical course/outcome in severely septic patients.MethodsThe study included 125 patients with severe sepsis/septic shock (SS) and 104 non-sepsis patients who were admitted to the intensive care unit (ICU) of Chiba University Hospital between October 2001 and September 2008 (discovery cohort) and 268 SS patients and 454 non-sepsis patients who were admitted to ICUs of five Japanese institutions including Chiba University Hospital between October 2008 and September 2012 (multi-center validation cohort). Three hundred forty seven healthy volunteers who consented to this study were also included. Genotyping was performed for a single-nucleotide polymorphism (SNP) within the coding region of IRGM, IRGM(+313) (rs10065172). Lipopolysaccharide challenge of whole blood from randomly selected healthy volunteers (n = 70) was performed for comparison of IRGM mRNA expression among different genotypes.ResultsNo significant difference in genotypic distributions (CC/CT/TT) at the IRGM(+313) locus was observed among the three subject groups (SS, non-sepsis, and healthy volunteers) in either cohort. When mortality were compared, no significant difference was observed in the non-sepsis group, while TT homozygotes exhibited a significantly higher mortality than the CC+CT genotype category in the SS group for both cohorts (P = 0.043, 0.037). Lipopolysaccharide challenge to whole blood showed a significant suppression of IRGM mRNA expression in TT compared with the CC+CT genotype category (P = 0.019).ConclusionsThe data suggest that the IRGM(+313), an autophagy-related polymorphic locus, influences outcome in severely septic patients, with the possible involvement of autophagy in sepsis exacerbation.

Dataset Information

Polymorphisms in Autophagy-Related Gene IRGM Are Associated with Susceptibility to Autoimmune Thyroid Diseases.

Publications

Polymorphisms in Autophagy-Related Gene <i>IRGM</i> Are Associated with Susceptibility to Autoimmune Thyroid Diseases.

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