Gene-environment interaction in the pathophysiology of type 1 diabetes
Type 1 diabetes (T1D) is a complex metabolic autoimmune disorder that affects millions of individuals worldwide and often leads to significant comorbidities. However, the precise trigger of autoimmunity and disease onset remain incompletely elucidated. This integrative perspective article synthesize...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2024.1335435/full |
| _version_ | 1797346175417843712 |
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| author | Rahul Mittal Nathanael Camick Nathanael Camick Joana R. N. Lemos Khemraj Hirani |
| author_facet | Rahul Mittal Nathanael Camick Nathanael Camick Joana R. N. Lemos Khemraj Hirani |
| author_sort | Rahul Mittal |
| collection | DOAJ |
| description | Type 1 diabetes (T1D) is a complex metabolic autoimmune disorder that affects millions of individuals worldwide and often leads to significant comorbidities. However, the precise trigger of autoimmunity and disease onset remain incompletely elucidated. This integrative perspective article synthesizes the cumulative role of gene-environment interaction in the pathophysiology of T1D. Genetics plays a significant role in T1D susceptibility, particularly at the major histocompatibility complex (MHC) locus and cathepsin H (CTSH) locus. In addition to genetics, environmental factors such as viral infections, pesticide exposure, and changes in the gut microbiome have been associated with the development of T1D. Alterations in the gut microbiome impact mucosal integrity and immune tolerance, increasing gut permeability through molecular mimicry and modulation of the gut immune system, thereby increasing the risk of T1D potentially through the induction of autoimmunity. HLA class II haplotypes with known effects on T1D incidence may directly correlate to changes in the gut microbiome, but precisely how the genes influence changes in the gut microbiome, and how these changes provoke T1D, requires further investigations. These gene-environment interactions are hypothesized to increase susceptibility to T1D through epigenetic changes such as DNA methylation and histone modification, which in turn modify gene expression. There is a need to determine the efficacy of new interventions that target these epigenetic modifications such as “epidrugs”, which will provide novel avenues for the effective management of T1D leading to improved quality of life of affected individuals and their families/caregivers. |
| first_indexed | 2024-03-08T11:29:09Z |
| format | Article |
| id | doaj.art-8bea2463270b4df7b2cb524dcd4dcb67 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-08T11:29:09Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-8bea2463270b4df7b2cb524dcd4dcb672024-01-26T04:30:27ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-01-011510.3389/fendo.2024.13354351335435Gene-environment interaction in the pathophysiology of type 1 diabetesRahul Mittal0Nathanael Camick1Nathanael Camick2Joana R. N. Lemos3Khemraj Hirani4Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, United StatesDiabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, United StatesHerbert Wertheim College of Medicine, Florida International University, Miami, FL, United StatesDiabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, United StatesDiabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, United StatesType 1 diabetes (T1D) is a complex metabolic autoimmune disorder that affects millions of individuals worldwide and often leads to significant comorbidities. However, the precise trigger of autoimmunity and disease onset remain incompletely elucidated. This integrative perspective article synthesizes the cumulative role of gene-environment interaction in the pathophysiology of T1D. Genetics plays a significant role in T1D susceptibility, particularly at the major histocompatibility complex (MHC) locus and cathepsin H (CTSH) locus. In addition to genetics, environmental factors such as viral infections, pesticide exposure, and changes in the gut microbiome have been associated with the development of T1D. Alterations in the gut microbiome impact mucosal integrity and immune tolerance, increasing gut permeability through molecular mimicry and modulation of the gut immune system, thereby increasing the risk of T1D potentially through the induction of autoimmunity. HLA class II haplotypes with known effects on T1D incidence may directly correlate to changes in the gut microbiome, but precisely how the genes influence changes in the gut microbiome, and how these changes provoke T1D, requires further investigations. These gene-environment interactions are hypothesized to increase susceptibility to T1D through epigenetic changes such as DNA methylation and histone modification, which in turn modify gene expression. There is a need to determine the efficacy of new interventions that target these epigenetic modifications such as “epidrugs”, which will provide novel avenues for the effective management of T1D leading to improved quality of life of affected individuals and their families/caregivers.https://www.frontiersin.org/articles/10.3389/fendo.2024.1335435/fulltype 1 diabetesgeneticsgene-environment interactionepigeneticsviral infectionspesticide exposure |
| spellingShingle | Rahul Mittal Nathanael Camick Nathanael Camick Joana R. N. Lemos Khemraj Hirani Gene-environment interaction in the pathophysiology of type 1 diabetes Frontiers in Endocrinology type 1 diabetes genetics gene-environment interaction epigenetics viral infections pesticide exposure |
| title | Gene-environment interaction in the pathophysiology of type 1 diabetes |
| title_full | Gene-environment interaction in the pathophysiology of type 1 diabetes |
| title_fullStr | Gene-environment interaction in the pathophysiology of type 1 diabetes |
| title_full_unstemmed | Gene-environment interaction in the pathophysiology of type 1 diabetes |
| title_short | Gene-environment interaction in the pathophysiology of type 1 diabetes |
| title_sort | gene environment interaction in the pathophysiology of type 1 diabetes |
| topic | type 1 diabetes genetics gene-environment interaction epigenetics viral infections pesticide exposure |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1335435/full |
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