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全基因组关联研究支持的非主要组织相容性复合体基因与1型糖尿病患者自身免疫性甲状腺炎的关联

Associations of GWAS-Supported Non-MHC Genes with Autoimmune Thyroiditis in Patients with Type 1 Diabetes.

作者信息

Liang Jialin, Liang Ganxiong, Liu Zhonghua, Cai Huan

机构信息

Department of Endocrinology and Metabolism, Zhongshan People's Hospital, Zhongshan, 528403, Guangdong, People's Republic of China.

Department of Rehabilitation, Zhongshan People's Hospital, Zhongshan, 528403, Guangdong, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2021 Jul 1;14:3017-3026. doi: 10.2147/DMSO.S319630. eCollection 2021.

Abstract

PURPOSE

A genome-wide association study (GWAS) in Caucasian population identified five non-MHC genes (, and ) associated with risk of the co-occurrence of autoimmune thyroid diseases (AITD) and type 1 diabetes (T1D). The aim of this study is to replicate these associations with AITD in patients with T1D in Chinese Han population.

PATIENTS AND METHODS

A case-control study was designed. Five single-nucleotide polymorphisms (SNPs) rs1111695, rs1217407, rs2153977, rs2358994, and rs7679475 were genotyped in 489 patients with T1D. Associations between genotypes and AITD risk were analyzed with logistic regression model.

RESULTS

AITD occurred in 159 (32.5%) patients. When adjusting multiple factors by logistic regression, rs7679475 was significantly associated with an increased risk of AITD in T1D patients in codominant model (G/G vs A/A, OR 2.93; 95% CI 1.44-5.96; = 0.003), dominant model (G/A-G/G vs A/A, OR 1.81; 95% CI 1.17-2.79; = 0.007) and recessive model (G/G vs A/A-G/A, OR 2.28; 95% CI 1.17-4.43; = 0.015). Furthermore, we found a significant interaction between rs7679475 and female ( = 0.005). In silico analysis indicated that rs7679475 is located in histone modification marked region and can change the binding of regulatory motifs.

CONCLUSION

Our results suggested that rs7679475 may influence the risk of AITD in patients with T1D in Chinese Han population, and this effect may be modulated by sex.

摘要

目的

一项针对白种人群的全基因组关联研究(GWAS)确定了五个与自身免疫性甲状腺疾病(AITD)和1型糖尿病(T1D)共病风险相关的非MHC基因(、和)。本研究的目的是在中国汉族T1D患者中重复这些基因与AITD的关联。

患者与方法

设计了一项病例对照研究。对489例T1D患者的五个单核苷酸多态性(SNP)rs1111695、rs1217407、rs2153977、rs2358994和rs7679475进行基因分型。采用逻辑回归模型分析基因型与AITD风险之间的关联。

结果

159例(32.5%)患者发生AITD。通过逻辑回归调整多个因素后,rs7679475在共显性模型(G/G vs A/A,OR 2.93;95%CI 1.44 - 5.96; = 0.003)、显性模型(G/A - G/G vs A/A,OR 1.81;95%CI 1.17 - 2.79; = 0.007)和隐性模型(G/G vs A/A - G/A,OR 2.28;95%CI 1.17 - 4.43; = 0.015)中与T1D患者AITD风险增加显著相关。此外,我们发现rs7679475与女性之间存在显著交互作用( = 0.005)。计算机模拟分析表明,rs7679475位于组蛋白修饰标记区域,可改变调控基序的结合。

结论

我们的结果表明,rs7679475可能影响中国汉族T1D患者患AITD的风险,且这种效应可能受性别调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f8/8257024/65d64e53eb23/DMSO-14-3017-g0001.jpg

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