TY - JOUR
T1 - Familial Linkage and Association of the NR3C1 Gene with Type 2 Diabetes and Depression Comorbidity
AU - Amin, Mutaz
AU - Syed, Shumail
AU - Wu, Rongling
AU - Postolache, Teodor Tudorel
AU - Gragnoli, Claudia
N1 - Funding Information:
This publication was supported in part with the funds received under Nebraska Laws 2021, LB 380, Section 109 awarded to C.G. (PI), Creighton University School of Medicine, through the Nebraska Department of Health & Human Services (DHHS). T.T.P. was supported, in part, by the Rocky Mountain MIRECC for suicide prevention, Aurora, CO. The content of the article expresses the views of the authors and does not necessarily represent the official positions of the State of Nebraska DHHS, or of the Veterans Health Administration.
Funding Information:
We thank the families who participated in the study, and we thank Bios Biotech Multi-Diagnostic Health Center, Rome, Italy, for data access and for financial, medical, and laboratory staff support. This publication was supported in part with the funds received under Nebraska Laws 2021, LB 380, Section 109 awarded to C.G. (PI), Creighton University School of Medicine, through the Nebraska Department of Health & Human Services (DHHS). T.T.P. was supported, in part, by the Rocky Mountain MIRECC for suicide prevention, Aurora, CO. The content of the article expresses the views of the authors and does not necessarily represent the official positions of the State of Nebraska DHHS, or of the Veterans Health Administration.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/10
Y1 - 2022/10
N2 - Impairment in the hypothalamic-pituitary-adrenal (HPA) axis and cortisol pathway may be major contributing factors to the common pathogenesis of major depressive disorders (MDD) and type 2 diabetes (T2D). A significant player in the neuroendocrine HPA axis and cortisol response is the glucocorticoid receptor (GR), which is encoded by the nuclear receptor subfamily 3 group C member (NR3C1) gene. Variants in the NR3C1 gene have been reported in patients with MDD and obesity and found to confer reduced risk for quantitative metabolic traits and T2D in Cushing syndrome; variants have not been reported in T2D and MDD-T2D comorbid patients. We studied 212 original Italian families with a rich family history for T2D and tested 24 single nucleotide polymorphisms (SNPs) in the NR3C1 gene for linkage to and linkage disequilibrium (LD) with T2D and MDD across different inheritance models. We identified a total of 6 novel SNPs significantly linked/in LD to/with T2D (rs6196, rs10482633, rs13186836, rs13184611, rs10482681 and rs258751) and 1 SNP (rs10482668) significantly linked to/in LD with both T2D and MDD. These findings expand understanding of the role that NR3C1 variants play in modulating the risk of T2D-MDD comorbidity. Replication and functional studies are needed to confirm these findings.
AB - Impairment in the hypothalamic-pituitary-adrenal (HPA) axis and cortisol pathway may be major contributing factors to the common pathogenesis of major depressive disorders (MDD) and type 2 diabetes (T2D). A significant player in the neuroendocrine HPA axis and cortisol response is the glucocorticoid receptor (GR), which is encoded by the nuclear receptor subfamily 3 group C member (NR3C1) gene. Variants in the NR3C1 gene have been reported in patients with MDD and obesity and found to confer reduced risk for quantitative metabolic traits and T2D in Cushing syndrome; variants have not been reported in T2D and MDD-T2D comorbid patients. We studied 212 original Italian families with a rich family history for T2D and tested 24 single nucleotide polymorphisms (SNPs) in the NR3C1 gene for linkage to and linkage disequilibrium (LD) with T2D and MDD across different inheritance models. We identified a total of 6 novel SNPs significantly linked/in LD to/with T2D (rs6196, rs10482633, rs13186836, rs13184611, rs10482681 and rs258751) and 1 SNP (rs10482668) significantly linked to/in LD with both T2D and MDD. These findings expand understanding of the role that NR3C1 variants play in modulating the risk of T2D-MDD comorbidity. Replication and functional studies are needed to confirm these findings.
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U2 - 10.3390/ijms231911951
DO - 10.3390/ijms231911951
M3 - Article
C2 - 36233250
AN - SCOPUS:85139965104
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 19
M1 - 11951
ER -