Association analysis between the TLR9 gene polymorphism rs352140 and type 1 diabetes

Yimeng Wang; Ying Xia; Yan Chen; Linling Xu; Xiaoxiao Sun; Jiaqi Li; Gan Huang; Xia Li; Zhiguo Xie; Zhiguang Zhou

doi:10.3389/fendo.2023.1030736

Association analysis between the TLR9 gene polymorphism rs352140 and type 1 diabetes

Front Endocrinol (Lausanne). 2023 Apr 17:14:1030736. doi: 10.3389/fendo.2023.1030736. eCollection 2023.

Authors

Yimeng Wang¹, Ying Xia¹, Yan Chen¹, Linling Xu¹, Xiaoxiao Sun¹, Jiaqi Li¹, Gan Huang¹, Xia Li¹, Zhiguo Xie¹, Zhiguang Zhou¹

Affiliation

¹ National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Abstract

Background: To a great extent, genetic factors contribute to the susceptibility to type 1 diabetes (T1D) development, and by triggering immune imbalance, Toll-like receptor (TLR) 9 is involved in the development of T1D. However, there is a lack of evidence supporting a genetic association between polymorphisms in the TLR9 gene and T1D.

Methods: In total, 1513 individuals, including T1D patients (n=738) and healthy control individuals (n=775), from the Han Chinese population were recruited for an association analysis of the rs352140 polymorphism of the TLR9 gene and T1D. rs352140 was genotyped by MassARRAY. The allele and genotype distributions of rs352140 in the T1D and healthy groups and those in different T1D subgroups were analyzed by the chi-squared test and binary logistic regression model. The chi-square test and Kruskal-Wallis H test were performed to explore the association between genotype and phenotype in T1D patients.

Results: The allele and genotype distributions of rs352140 were significantly different in T1D patients and healthy control individuals (p=0.019, p=0.035). Specifically, the T allele and TT genotype of rs352140 conferred a higher risk of T1D (OR=1.194, 95% CI=1.029-1.385, p=0.019, OR=1.535, 95% CI=1.108-2.126, p=0.010). The allele and genotype distributions of rs352140 were not significantly different between childhood-onset and adult-onset T1D and between T1D with a single islet autoantibody and T1D with multiple islet autoantibodies (p=0.603, p=0.743). rs352140 was associated with T1D susceptibility according to the recessive and additive models (p=0.015, p=0.019) but was not associated with T1D susceptibility in the dominant and overdominant models (p=0.117, p=0.928). Moreover, genotype-phenotype association analysis showed that the TT genotype of rs352140 was associated with higher fasting C-peptide levels (p=0.017).

Conclusion: In the Han Chinese population, the TLR9 polymorphism rs352140 is associated with T1D and is a risk factor for susceptibility to T1D.

Keywords: autoimmunity; immunotherapy; polymorphism; toll-like receptor; type 1 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 1* / epidemiology
Diabetes Mellitus, Type 1* / genetics
Genetic Predisposition to Disease
Genotype
Humans
Polymorphism, Single Nucleotide
Toll-Like Receptor 9 / genetics

Substances

Toll-Like Receptor 9
TLR9 protein, human

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81873634 and 82070813), the Hunan Province Natural Science Foundation of China (Grant Nos. 2022JJ30858, 2022JJ30851, 2018JJ2573 and 2020JJ2053), the Science and Technology Innovation Program of Hunan Province (Grant No. 2022RC1010), the Hunan Provincial Innovation Foundation for Postgraduate (Grant No. CX20220120) and the Fundamental Research Funds for the Central Universities of Central South University (Grant No. 2022ZZTS0029).