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Evaluation of the Host Genetic Effects of Tuberculosis-Associated Variants Among Patients With Type 1 and Type 2 Diabetes Mellitus

BACKGROUND: Understanding the link between tuberculosis (TB) and diabetes is increasingly important as public health responds to the growing global burden of noncommunicable diseases. Genetic association studies have identified numerous host genetic variants linked to TB; however, potential host gen...

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Autores principales: Zhong, Huimin, Magee, Matthew J, Huang, Yunfeng, Hui, Qin, Gwinn, Marta, Gandhi, Neel R, Sun, Yan V
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166116/
https://www.ncbi.nlm.nih.gov/pubmed/32328508
http://dx.doi.org/10.1093/ofid/ofaa106
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author Zhong, Huimin
Magee, Matthew J
Huang, Yunfeng
Hui, Qin
Gwinn, Marta
Gandhi, Neel R
Sun, Yan V
author_facet Zhong, Huimin
Magee, Matthew J
Huang, Yunfeng
Hui, Qin
Gwinn, Marta
Gandhi, Neel R
Sun, Yan V
author_sort Zhong, Huimin
collection PubMed
description BACKGROUND: Understanding the link between tuberculosis (TB) and diabetes is increasingly important as public health responds to the growing global burden of noncommunicable diseases. Genetic association studies have identified numerous host genetic variants linked to TB; however, potential host genetic mechanisms linking TB and diabetes remain unexplored. METHODS: We used genetic and phenotypic data from the UK Biobank to evaluate the association of 6 previously reported TB-related host genetic variants (genome-wide significant associations from published studies) with diabetes. The study included 409( )692 adults of European ancestry including 2177 with type 1 diabetes mellitus (T1DM) and 13( )976 with type 2 diabetes mellitus (T2DM), defined by ICD-10 diagnosis codes. RESULTS: Of the 6 TB-associated single nucleotide polymorphisms (SNPs), 2 were associated with T1DM and 3 with T2DM, after adjusting for age, sex, body mass index, smoking, alcohol use, and population structure. After correction for multiple testing, SNPs rs2894257 and rs3135359 (HLA-DRA-DQA1) were associated with T1DM (rs2894257: odds ratio [OR], 1.32; 95% confidence interval [CI], 1.21–1.45; rs3135359: OR, 1.72; 95% CI, 1.57–1.88) and T2DM (rs2894257: OR, 1.11; 95% CI, 1.08–1.15; rs3135359: OR, 1.06; 95% CI, 1.025–1.096). The associations with T2DM weakened for rs2894257 and rs3135359 after further exclusion of probable T1DM cases defined by International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes. SNP rs4733781 on chromosome 8 (ASAP1 gene) was associated with T2DM after exclusion of T1DM cases. CONCLUSIONS: Our findings suggest that common host genetic effects may play a role in the molecular mechanism linking TB and diabetes. Future large genetic studies of TB and diabetes should focus on developing countries with high burdens of infectious and chronic diseases.
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spelling pubmed-71661162020-04-23 Evaluation of the Host Genetic Effects of Tuberculosis-Associated Variants Among Patients With Type 1 and Type 2 Diabetes Mellitus Zhong, Huimin Magee, Matthew J Huang, Yunfeng Hui, Qin Gwinn, Marta Gandhi, Neel R Sun, Yan V Open Forum Infect Dis Major Article BACKGROUND: Understanding the link between tuberculosis (TB) and diabetes is increasingly important as public health responds to the growing global burden of noncommunicable diseases. Genetic association studies have identified numerous host genetic variants linked to TB; however, potential host genetic mechanisms linking TB and diabetes remain unexplored. METHODS: We used genetic and phenotypic data from the UK Biobank to evaluate the association of 6 previously reported TB-related host genetic variants (genome-wide significant associations from published studies) with diabetes. The study included 409( )692 adults of European ancestry including 2177 with type 1 diabetes mellitus (T1DM) and 13( )976 with type 2 diabetes mellitus (T2DM), defined by ICD-10 diagnosis codes. RESULTS: Of the 6 TB-associated single nucleotide polymorphisms (SNPs), 2 were associated with T1DM and 3 with T2DM, after adjusting for age, sex, body mass index, smoking, alcohol use, and population structure. After correction for multiple testing, SNPs rs2894257 and rs3135359 (HLA-DRA-DQA1) were associated with T1DM (rs2894257: odds ratio [OR], 1.32; 95% confidence interval [CI], 1.21–1.45; rs3135359: OR, 1.72; 95% CI, 1.57–1.88) and T2DM (rs2894257: OR, 1.11; 95% CI, 1.08–1.15; rs3135359: OR, 1.06; 95% CI, 1.025–1.096). The associations with T2DM weakened for rs2894257 and rs3135359 after further exclusion of probable T1DM cases defined by International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes. SNP rs4733781 on chromosome 8 (ASAP1 gene) was associated with T2DM after exclusion of T1DM cases. CONCLUSIONS: Our findings suggest that common host genetic effects may play a role in the molecular mechanism linking TB and diabetes. Future large genetic studies of TB and diabetes should focus on developing countries with high burdens of infectious and chronic diseases. Oxford University Press 2020-03-26 /pmc/articles/PMC7166116/ /pubmed/32328508 http://dx.doi.org/10.1093/ofid/ofaa106 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Article
Zhong, Huimin
Magee, Matthew J
Huang, Yunfeng
Hui, Qin
Gwinn, Marta
Gandhi, Neel R
Sun, Yan V
Evaluation of the Host Genetic Effects of Tuberculosis-Associated Variants Among Patients With Type 1 and Type 2 Diabetes Mellitus
title Evaluation of the Host Genetic Effects of Tuberculosis-Associated Variants Among Patients With Type 1 and Type 2 Diabetes Mellitus
title_full Evaluation of the Host Genetic Effects of Tuberculosis-Associated Variants Among Patients With Type 1 and Type 2 Diabetes Mellitus
title_fullStr Evaluation of the Host Genetic Effects of Tuberculosis-Associated Variants Among Patients With Type 1 and Type 2 Diabetes Mellitus
title_full_unstemmed Evaluation of the Host Genetic Effects of Tuberculosis-Associated Variants Among Patients With Type 1 and Type 2 Diabetes Mellitus
title_short Evaluation of the Host Genetic Effects of Tuberculosis-Associated Variants Among Patients With Type 1 and Type 2 Diabetes Mellitus
title_sort evaluation of the host genetic effects of tuberculosis-associated variants among patients with type 1 and type 2 diabetes mellitus
topic Major Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166116/
https://www.ncbi.nlm.nih.gov/pubmed/32328508
http://dx.doi.org/10.1093/ofid/ofaa106
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