Diabetes, Metabolic Syndrome and Obesity (Jul 2021)

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

  • Liang J,
  • Liang G,
  • Liu Z,
  • Cai H

Journal volume & issue
Vol. Volume 14
pp. 3017 – 3026

Abstract

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Jialin Liang,1 Ganxiong Liang,1 Zhonghua Liu,2 Huan Cai2 1Department of Endocrinology and Metabolism, Zhongshan People’s Hospital, Zhongshan, 528403, Guangdong, People’s Republic of China; 2Department of Rehabilitation, Zhongshan People’s Hospital, Zhongshan, 528403, Guangdong, People’s Republic of ChinaCorrespondence: Ganxiong LiangDepartment of Endocrinology and Metabolism, Zhongshan People’s Hospital, 2 East Sunwen Road, Zhongshan, 528403, Guangdong, People’s Republic of ChinaTel +86-13392926029Email [email protected] CaiDepartment of Rehabilitation, Zhongshan People’s Hospital, 2 East Sunwen Road, Zhongshan, 528403, Guangdong, People’s Republic of ChinaTel +86-18718750210Email [email protected]: A genome-wide association study (GWAS) in Caucasian population identified five non-MHC genes (PHTF1, PTPN22, MAGI3, BCL2L15, and QRFPR) 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) PHTF1 rs1111695, PTPN22 rs1217407, MAGI3 rs2153977, BCL2L15 rs2358994, and QRFPR 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, QRFPR 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; P = 0.003), dominant model (G/A-G/G vs A/A, OR 1.81; 95% CI 1.17– 2.79; P = 0.007) and recessive model (G/G vs A/A-G/A, OR 2.28; 95% CI 1.17– 4.43; P = 0.015). Furthermore, we found a significant interaction between rs7679475 and female (P interaction = 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 QRFPR rs7679475 may influence the risk of AITD in patients with T1D in Chinese Han population, and this effect may be modulated by sex.Keywords: autoimmune thyroid diseases, type 1 diabetes, single-nucleotide polymorphism, QRFPR gene

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