Assessment of Association between NINJ2 Polymorphisms and Suicide Attempts in an Iranian Population

Safa, Amin; Omrani, Mir Davood; Nicknafs, Fwad; Oskooei, Vahid Kholghi; Ghafouri‐Fard, Soudeh

doi:10.1007/s12031-020-01584-x

Cited by 7 publications

(3 citation statements)

References 21 publications

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“…Variants in NINJ2 have also been associated with obsessive‐compulsive disorder [33], endometrial cancer [34], suicide attempts [35], and multiple sclerosis [36]. Results of GWAS indicated that variants in the linkage disequilibrium (LD) block, including NINJ2 (chr12:61107–1,080,331, hg19), were significantly associated with metabolic‐related phenotypes, including body mass index (BMI), waist circumference, body weight, waist‐hip ratio, body fat percentage, and basal metabolic rate, according to the CAUSALdb data base (Supporting Information Figure S11A) [37].…”

Section: Discussionmentioning

confidence: 99%

NINJ2 deficiency inhibits preadipocyte differentiation and promotes insulin resistance through regulating insulin signaling

Peng

Wang

et al. 2022

Obesity

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Objective Genetic variants in ninjurin‐2 (NINJ2; nerve injury‐induced protein 2) confer risk of ischemic strokes and coronary artery disease as well as endothelial activation and inflammation. However, little is known about NINJ2's in vivo functions and underlying mechanisms. Methods The phenotypes of NINJ2 knockout mice were analyzed, and mechanisms of NINJ2 that regulate body weight, insulin resistance, and glucose homeostasis and lipogenesis were investigated in vivo and in vitro. Results This study found that mice lacking NINJ2 showed impaired adipogenesis, increased insulin resistance, and abnormal glucose homeostasis, all of which are risk factors for strokes and coronary artery disease. Mechanistically, NINJ2 directly interacts with insulin receptor/insulin‐like growth factor 1 receptor (INSR/IGF1R), and NINJ2 knockdown can block insulin‐induced mitotic clonal expansion during preadipocyte differentiation by inhibiting protein kinase B/extracellular signal‐regulated kinase (AKT/ERK) signaling and by decreasing the expression of key adipocyte transcriptional regulators CCAAT/enhancer‐binding protein β (C/EBP‐β), C/EBP‐α, and peroxisome proliferator‐activated receptor γ (PPAR‐γ). Furthermore, the interaction between NINJ2 and INSR/IGF1R is needed for maintaining insulin sensitivity in adipocytes and muscle via AKT and glucose transporter type 4. Notably, adenovirus‐mediated NINJ2 overexpression can ameliorate diet‐induced insulin resistance in mice. Conclusions In conclusion, these findings reveal NINJ2 as an important new facilitator of insulin receptors, and the authors propose a unique regulatory mechanism between insulin signaling, adipogenesis, and insulin resistance.

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Section: Discussionmentioning

confidence: 99%

NINJ2 deficiency inhibits preadipocyte differentiation and promotes insulin resistance through regulating insulin signaling

Peng

Wang

et al. 2022

Obesity

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“…We found it interesting to study the polymorphisms associated with suicide in a dementia cohort. In our study, we selected some SNPs that have been associated with suicidal behavior in earlier studies— rs9475195 , rs7982251 , rs3781878 , rs165774 [ 28 ], rs2834789 , rs10898553 [ 29 ], rs358592 [ 30 ], rs4918918 , rs2462021 [ 31 ], rs10903034 [ 32 ], rs16841143 [ 26 ], rs11833579 [ 33 ], rs7296262 [ 34 ], and rs3806263 [ 35 ]—and assessed the frequency of these genotypes in older adults diagnosed with dementia compared with their healthy peers. We selected polymorphisms that showed significant associations with suicide according to the GWAS as well as some other selected studies and that had a minor allele frequency in the European population of at least 10%.…”

Section: Introductionmentioning

confidence: 99%

Suicide-Related Single Nucleotide Polymorphisms, rs4918918 and rs10903034: Association with Dementia in Older Adults

Abramova

Solovevа²,

Zorkina

et al. 2022

Genes

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Dementia has enormous implications for patients and the health care system. Genetic markers are promising for detecting the risk of cognitive impairment. We hypothesized that genetic variants associated with suicide risk might significantly increase the risk of cognitive decline because suicide in older adults is often a consequence of cognitive impairment. We investigated several single-nucleotide polymorphisms that were initially associated with suicide risk in dementia older adults and identified the APOE gene alleles. The study was performed with subjects over the age of 65: 112 patients with dementia and 146 healthy volunteers. The MMSE score was used to assess cognitive functions. Study participants were genotyped using real-time PCR (APOE: rs429358, rs7412; genes associated with suicide: rs9475195, rs7982251, rs2834789, rs358592, rs4918918, rs3781878, rs10903034, rs165774, rs16841143, rs11833579 rs10898553, rs7296262, rs3806263, and rs2462021). Genotype analysis revealed the significance of APOEε4, APOEε2, and rs4918918 (SORBS1) when comparing dementia and healthy control groups. The association of APOEε4, APOEε2, and rs10903034 (IFNLR1) with the overall MMSE score was indicated. The study found an association with dementia of rs4918918 (SORBS1) and rs10903034 (IFNLR1) previously associated with suicide and confirmed the association of APOEε4 and APOEε2 with dementia.

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“…Single nucleotide polymorphisms studies points out that mutations of Ninj2 could be risk factors of ischemic stroke and multiple sclerosis, [ 11 ] and even associated with suicide attempts. [ 12 ] Recent studies indicate that the expression of Ninj2 is downregulated in mice with stress‐induced depression. [ 13 ] However, whether and how Ninj2 plays a role in the development of depression is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Dysmyelination by Oligodendrocyte‐Specific Ablation of Ninj2 Contributes to Depressive‐Like Behaviors

Sun

Chen

et al. 2021

Advanced Science

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Depression is a mental disorder affecting more than 300 million people in the world. Abnormalities in white matter are associated with the development of depression. Here, the authors show that mice with oligodendrocyte-specific deletion of Nerve injury-induced protein 2 (Ninj2) exhibit depressive-like behaviors. Loss of Ninj2 in oligodendrocytes inhibits oligodendrocyte development and myelination, and impairs neuronal structure and activities. Ninj2 competitively inhibits TNF𝜶/TNFR1 signaling pathway by directly binding to TNFR1 in oligodendrocytes. Loss of Ninj2 activates TNF𝜶-induced necroptosis, and increases C-C Motif Chemokine Ligand 2 (Ccl2) production, which might mediate the signal transduction from oligodendrocyte to neurons. Inhibition of necroptosis by Nec-1s administration synchronously restores oligodendrocyte development, improves neuronal excitability, and alleviates depressive-like behaviors. This study thus illustrates the role of Ninj2 in the development of depression and myelination, reveals the relationship between oligodendrocytes and neurons, and provides a potential therapeutic target for depression.

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Assessment of Association between NINJ2 Polymorphisms and Suicide Attempts in an Iranian Population

Cited by 7 publications

References 21 publications

NINJ2 deficiency inhibits preadipocyte differentiation and promotes insulin resistance through regulating insulin signaling

NINJ2 deficiency inhibits preadipocyte differentiation and promotes insulin resistance through regulating insulin signaling

Suicide-Related Single Nucleotide Polymorphisms, rs4918918 and rs10903034: Association with Dementia in Older Adults

Dysmyelination by Oligodendrocyte‐Specific Ablation of Ninj2 Contributes to Depressive‐Like Behaviors

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