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Comorbidity of CRHR2 gene variants in type 2 diabetes and depression

INTRODUCTION: The corticotropin-releasing hormone receptor 2 (CRHR2) gene encodes CRHR2, which is an important element in the hypothalamic-pituitary-adrenal physiologic response towards stress culminating in hyperglycemia, insulin resistance, mood disorders and depression (MDD). CRHR2-/- mice are hy...

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Autores principales: Amin, M., Ott, J., Wu, R., Postolache, T., Vergare, M., Gragnoli, C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9565289/
http://dx.doi.org/10.1192/j.eurpsy.2022.1050
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author Amin, M.
Ott, J.
Wu, R.
Postolache, T.
Vergare, M.
Gragnoli, C.
author_facet Amin, M.
Ott, J.
Wu, R.
Postolache, T.
Vergare, M.
Gragnoli, C.
author_sort Amin, M.
collection PubMed
description INTRODUCTION: The corticotropin-releasing hormone receptor 2 (CRHR2) gene encodes CRHR2, which is an important element in the hypothalamic-pituitary-adrenal physiologic response towards stress culminating in hyperglycemia, insulin resistance, mood disorders and depression (MDD). CRHR2-/- mice are hypersensitive to stress, and the CRHR2 locus in humans has been linked to type 2 diabetes (T2D) and MDD. OBJECTIVES: Several variants in the CRHR2 gene have been reported in patients with bipolar disorder, post-traumatic stress disorder, and T2D, but variants in the gene have not been investigated in families with T2D and MDD. METHODS: We genotyped 212 Italian families with T2D and MDD. We tested 17 SNPs in the CRHR2 gene using two-point parametric-linkage and linkage-disequilibrium (LD) analysis with the following models: dominant with complete-penetrance (D1), dominant with incomplete-penetrance (D2), recessive with complete-penetrance (R1) and recessive with incomplete-penetrance (R2). RESULTS: We detected linkage to and/or LD with: MDD for 3 SNPs/D1, 2 SNPs/D2, 3 SNPs/R1, and 3 SNPs/R2; and, T2D for 3 SNPs/D1, 2 SNPs/D2, 2 SNPs/R1 and 1 SNP/R2. Two independent SNPs were comorbid. Interestingly, the variants linked to or in LD with MDD had in general higher statistical significance level than the variants linked to T2D, despite that the families were primarily ascertained for T2D. CONCLUSIONS: Our study shows for the first time that the CRHR2 gene which encodes CRHR2 is in linkage to and linkage disequilibrium with MDD and T2D, thereby contributing, in families with T2D, to both disorders and underlying the shared genetic pathogenesis of their comorbidity DISCLOSURE: No significant relationships.
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spelling pubmed-95652892022-10-17 Comorbidity of CRHR2 gene variants in type 2 diabetes and depression Amin, M. Ott, J. Wu, R. Postolache, T. Vergare, M. Gragnoli, C. Eur Psychiatry Abstract INTRODUCTION: The corticotropin-releasing hormone receptor 2 (CRHR2) gene encodes CRHR2, which is an important element in the hypothalamic-pituitary-adrenal physiologic response towards stress culminating in hyperglycemia, insulin resistance, mood disorders and depression (MDD). CRHR2-/- mice are hypersensitive to stress, and the CRHR2 locus in humans has been linked to type 2 diabetes (T2D) and MDD. OBJECTIVES: Several variants in the CRHR2 gene have been reported in patients with bipolar disorder, post-traumatic stress disorder, and T2D, but variants in the gene have not been investigated in families with T2D and MDD. METHODS: We genotyped 212 Italian families with T2D and MDD. We tested 17 SNPs in the CRHR2 gene using two-point parametric-linkage and linkage-disequilibrium (LD) analysis with the following models: dominant with complete-penetrance (D1), dominant with incomplete-penetrance (D2), recessive with complete-penetrance (R1) and recessive with incomplete-penetrance (R2). RESULTS: We detected linkage to and/or LD with: MDD for 3 SNPs/D1, 2 SNPs/D2, 3 SNPs/R1, and 3 SNPs/R2; and, T2D for 3 SNPs/D1, 2 SNPs/D2, 2 SNPs/R1 and 1 SNP/R2. Two independent SNPs were comorbid. Interestingly, the variants linked to or in LD with MDD had in general higher statistical significance level than the variants linked to T2D, despite that the families were primarily ascertained for T2D. CONCLUSIONS: Our study shows for the first time that the CRHR2 gene which encodes CRHR2 is in linkage to and linkage disequilibrium with MDD and T2D, thereby contributing, in families with T2D, to both disorders and underlying the shared genetic pathogenesis of their comorbidity DISCLOSURE: No significant relationships. Cambridge University Press 2022-09-01 /pmc/articles/PMC9565289/ http://dx.doi.org/10.1192/j.eurpsy.2022.1050 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstract
Amin, M.
Ott, J.
Wu, R.
Postolache, T.
Vergare, M.
Gragnoli, C.
Comorbidity of CRHR2 gene variants in type 2 diabetes and depression
title Comorbidity of CRHR2 gene variants in type 2 diabetes and depression
title_full Comorbidity of CRHR2 gene variants in type 2 diabetes and depression
title_fullStr Comorbidity of CRHR2 gene variants in type 2 diabetes and depression
title_full_unstemmed Comorbidity of CRHR2 gene variants in type 2 diabetes and depression
title_short Comorbidity of CRHR2 gene variants in type 2 diabetes and depression
title_sort comorbidity of crhr2 gene variants in type 2 diabetes and depression
topic Abstract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9565289/
http://dx.doi.org/10.1192/j.eurpsy.2022.1050
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