Cargando…

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

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 po...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Yimeng, Xia, Ying, Chen, Yan, Xu, Linling, Sun, Xiaoxiao, Li, Jiaqi, Huang, Gan, Li, Xia, Xie, Zhiguo, Zhou, Zhiguang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150994/
https://www.ncbi.nlm.nih.gov/pubmed/37139337
http://dx.doi.org/10.3389/fendo.2023.1030736
_version_ 1785035451247099904
author Wang, Yimeng
Xia, Ying
Chen, Yan
Xu, Linling
Sun, Xiaoxiao
Li, Jiaqi
Huang, Gan
Li, Xia
Xie, Zhiguo
Zhou, Zhiguang
author_facet Wang, Yimeng
Xia, Ying
Chen, Yan
Xu, Linling
Sun, Xiaoxiao
Li, Jiaqi
Huang, Gan
Li, Xia
Xie, Zhiguo
Zhou, Zhiguang
author_sort Wang, Yimeng
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10150994
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-101509942023-05-02 Association analysis between the TLR9 gene polymorphism rs352140 and type 1 diabetes Wang, Yimeng Xia, Ying Chen, Yan Xu, Linling Sun, Xiaoxiao Li, Jiaqi Huang, Gan Li, Xia Xie, Zhiguo Zhou, Zhiguang Front Endocrinol (Lausanne) Endocrinology 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. Frontiers Media S.A. 2023-04-17 /pmc/articles/PMC10150994/ /pubmed/37139337 http://dx.doi.org/10.3389/fendo.2023.1030736 Text en Copyright © 2023 Wang, Xia, Chen, Xu, Sun, Li, Huang, Li, Xie and Zhou https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Wang, Yimeng
Xia, Ying
Chen, Yan
Xu, Linling
Sun, Xiaoxiao
Li, Jiaqi
Huang, Gan
Li, Xia
Xie, Zhiguo
Zhou, Zhiguang
Association analysis between the TLR9 gene polymorphism rs352140 and type 1 diabetes
title Association analysis between the TLR9 gene polymorphism rs352140 and type 1 diabetes
title_full Association analysis between the TLR9 gene polymorphism rs352140 and type 1 diabetes
title_fullStr Association analysis between the TLR9 gene polymorphism rs352140 and type 1 diabetes
title_full_unstemmed Association analysis between the TLR9 gene polymorphism rs352140 and type 1 diabetes
title_short Association analysis between the TLR9 gene polymorphism rs352140 and type 1 diabetes
title_sort association analysis between the tlr9 gene polymorphism rs352140 and type 1 diabetes
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150994/
https://www.ncbi.nlm.nih.gov/pubmed/37139337
http://dx.doi.org/10.3389/fendo.2023.1030736
work_keys_str_mv AT wangyimeng associationanalysisbetweenthetlr9genepolymorphismrs352140andtype1diabetes
AT xiaying associationanalysisbetweenthetlr9genepolymorphismrs352140andtype1diabetes
AT chenyan associationanalysisbetweenthetlr9genepolymorphismrs352140andtype1diabetes
AT xulinling associationanalysisbetweenthetlr9genepolymorphismrs352140andtype1diabetes
AT sunxiaoxiao associationanalysisbetweenthetlr9genepolymorphismrs352140andtype1diabetes
AT lijiaqi associationanalysisbetweenthetlr9genepolymorphismrs352140andtype1diabetes
AT huanggan associationanalysisbetweenthetlr9genepolymorphismrs352140andtype1diabetes
AT lixia associationanalysisbetweenthetlr9genepolymorphismrs352140andtype1diabetes
AT xiezhiguo associationanalysisbetweenthetlr9genepolymorphismrs352140andtype1diabetes
AT zhouzhiguang associationanalysisbetweenthetlr9genepolymorphismrs352140andtype1diabetes