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Comorbidity of CRHR2 gene variants in type 2 diabetes and depression

Published online by Cambridge University Press:  01 September 2022

M. Amin ,
J. Ott ,
R. Wu ,
T. Postolache ,
M. Vergare  and
C. Gragnoli
M. Amin*
Affiliation:
Faculty of Medicine, University of Khartoum, Department Of Biochemistry And Molecular Biology, Khartoum, Sudan
J. Ott
Affiliation:
Rockefeller University, Laboratory Of Statistical Genetics, New York, United States of America
R. Wu
Affiliation:
Penn State College of Medicine, Department Of Public Health Sciences, Hershey, United States of America Penn State College of Medicine, Departments Of Statistics, Hershey, United States of America
T. Postolache
Affiliation:
University of Maryland School of Medicine, Mood And Anxiety Program, Department Of Psychiatry, Baltimore, United States of America Veterans Integrated Service Network (VISN) 5, VA Capitol Health Care Network, Rocky Mountain Mental Illness Research Education And Clinical Center (mirecc), Veterans Integrated Service Network (visn), Denver, United States of America Veterans Integrated Service Network (VISN) 5, VA Capitol Health Care Network, Mental Illness Research Education And Clinical Center (mirecc), Baltimore, United States of America
M. Vergare
Affiliation:
Sidney Kimmel Medical College, Thomas Jefferson University, Department Of Psychiatry And Human Behavior, Philadelphia, United States of America
C. Gragnoli
Affiliation:
Penn State College of Medicine, Department Of Public Health Sciences, Hershey, United States of America Creighton University School of Medicine, Division Of Endocrinology, Department Of Medicine, Philadelphia, United States of America Bios Biotech Multi-Diagnostic Health Center, Molecular Biology Laboratory, Rome, Italy
*
*Corresponding author.

Abstract

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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.

Keywords

Type 2 diabetesDepressionCRHR2MDD
Type
Abstract
Information
European Psychiatry , Volume 65 , Special Issue S1: Abstracts of the 30th European Congress of Psychiatry , June 2022 , pp. S414
Creative Commons
Creative Common License - CCCreative Common License - BY
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.
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of the European Psychiatric Association
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