The CRHR1 Gene Contributes to Genetic Susceptibility of Aggressive Behavior Towards Others in Chinese Southwest Han Population

Chen, Bifeng; Gu, Tao; Ma, Bo; Zheng, Guoan; Ke, Bingxiong; Zhang, Xiufeng; Zhang, Lirui; Wang, Yuanyuan; Hu, Liping; Chen, Yang; Qiu, Jianbo; Nie, Shengjie

doi:10.1007/s12031-013-0160-z

Cited by 34 publications

(10 citation statements)

References 23 publications

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“…Therefore, CRHR1 deficiency leads to impaired stress response [40,41]. CRHR1 polymorphisms have been previously associated with depressive disorders [26,42,43] and with suicidal and aggressive behaviours, symptoms frequently observed in subjects with BPD [44,45]. Our results may support the hypothesis of the involvement of CRHR1 on BPD.…”

Section: Discussionsupporting

confidence: 85%

The role of hypothalamus–pituitary–adrenal genes and childhood trauma in borderline personality disorder

Martín-Blanco

Ferrer

Soler

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus-pituitary-adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis. The aim of this study was to investigate the contribution of genetic variants in the HPA axis and to explore the modulating effect of childhood trauma in a large sample of BPD patients and controls. DNA was obtained from a sample of 481 subjects with BPD and 442 controls. Case-control differences in allelic frequencies of 47 polymorphisms in 10 HPA axis genes were analysed. Modulation of genetic associations by the presence of childhood trauma was also investigated by dividing the sample into three groups: BPD with trauma, BPD without trauma and controls. Two FKBP5 polymorphisms (rs4713902-C and rs9470079-A) showed significant associations with BPD. There were also associations between BPD and haplotype combinations of the genes FKBP5 and CRHR1. Two FKBP5 alleles (rs3798347-T and rs10947563-A) were more frequent in BPD subjects with history of physical abuse and emotional neglect and two CRHR2 variants (rs4722999-C and rs12701020-C) in BPD subjects with sexual and physical abuse. Our findings suggest a contribution of HPA axis genetic variants to BPD pathogenesis and reinforce the hypothesis of the modulating effect of childhood trauma in the development of this disorder.

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Section: Discussionsupporting

confidence: 85%

The role of hypothalamus–pituitary–adrenal genes and childhood trauma in borderline personality disorder

Martín-Blanco

Ferrer

Soler

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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“…Although animal models show a strong relation between the HPA axis and aggression only few genetic association studies in human individuals have been performed. In a Chinese southwest Han population, a single marker and haplotype analysis of three variants (rs4458044G>C, rs242924T>G, and rs17689966G>A) of the CRH receptor gene CRHR1 on Chr 17q21.31 showed significant association of the G‐G‐A haplotype with an increased susceptibility of AB toward others [Chen et al, ]. This receptor is located on the cells of the pituitary gland and activates a protein kinase A (PKA) signaling cascade triggering pro‐opiomelanocortin (POMC) transcription.…”

Section: Methodsmentioning

confidence: 99%

The neurobiological basis of human aggression: A review on genetic and epigenetic mechanisms

Waltes

Chiocchetti

Freitag

2015

American J of Med Genetics Pt B

146

105

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Aggression is an evolutionary conserved behavior present in most species including humans. Inadequate aggression can lead to long-term detrimental personal and societal effects. Here, we differentiate between proactive and reactive forms of aggression and review the genetic determinants of it. Heritability estimates of aggression in general vary between studies due to differing assessment instruments for aggressive behavior (AB) as well as age and gender of study participants. In addition, especially non-shared environmental factors shape AB. Current hypotheses suggest that environmental effects such as early life stress or chronic psychosocial risk factors (e.g., maltreatment) and variation in genes related to neuroendocrine, dopaminergic as well as serotonergic systems increase the risk to develop AB. In this review, we summarize the current knowledge of the genetics of human aggression based on twin studies, genetic association studies, animal models, and epigenetic analyses with the aim to differentiate between mechanisms associated with proactive or reactive aggression. We hypothesize that from a genetic perspective, the aminergic systems are likely to regulate both reactive and proactive aggression, whereas the endocrine pathways seem to be more involved in regulation of reactive aggression through modulation of impulsivity. Epigenetic studies on aggression have associated non-genetic risk factors with modifications of the stress response and the immune system. Finally, we point to the urgent need for further genome-wide analyses and the integration of genetic and epigenetic information to understand individual differences in reactive and proactive AB.

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“…MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), MTHFR G1793A (rs2274976), and SLC19A1 G80A (rs1051266) polymorphisms were genotyped by a patented multiplex LDR method (iMLDR, Genesky Bio-Tech Cod., Ltd., Shanghai, China) [24], with technical support from the Shanghai Genesky Biotechnology Company (Shanghai, China). Finally, the samples were analyzed by the ABI3130XL sequencer (Applied Biosystems, Foster City, CA, USA) and the raw data were analyzed by GeneMapper4.1 (Applied Biosystems, Foster City, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Association of MTHFR, SLC19A1 Genetic Polymorphism, Serum Folate, Vitamin B12 and Hcy Status with Cognitive Functions in Chinese Adults

et al. 2016

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Background/Aim: Studies have indicated a relationship between either gene polymorphism or in vivo B vitamins’ nutritional status with cognition in the elderly. However, the combined effects of MTHFR and SLC19A1gene polymorphism with serum folate and vitamin B12 levels on cognition in Chinese adult population remain unclear. Methods: Demographic information of 426 Chinese adults aged from 55 to 90 were collected by a well designed self-administered questionnaire. The Montreal Cognitive Assessment test was utilized to evaluate the cognition status of the participants. MTHFR and SLC19A1 genotyping was analyzed using polymerase chain reaction-ligase detection reaction (PCR- LDR) method. Serum folate, vitamin B12 and homocysteine (Hcy) levels were detected by commercial assay kits. Pearson’s correlation was used for data analyses and statistical significance was set at p < 0.05. Results: Serum Hcylevels demonstrated a negative correlation with serum folate (r = −0.301) and vitamin B12 (r = −0.292) levels. The negative correlation found between serum Hcy levels and attention ability was observed in all 426 studied subjects (r = −0.122). Subjects with MTHFR 677 T/T and 1298 A/A genotypes demonstrated a higher serum Hcy levels (p < 0.05). Carriers of MTHFR (1298 A/C + C/C and 1793 G/A) and SLC19A1 80 G/G genotypes showed lower abstraction and delayed memory ability, respectively (p < 0.05). Subjects with MTHFR 1793 G/A genotype along with low serum folate concentration demonstrated the lowest name and orientation abilities. The effects of MTHFR 1793 G/A genotype on cognitive performance were dependent on the status of serum vitamin B12. Conclusion: Cognition of adults was associated with MTHFR, SLC19A1 gene polymorphism and serum Hcy levels. This study clearly establishes a combined effect of MTHFR gene polymorphism and serum B vitamins levels on cognition in Chinese adults.

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The CRHR1 Gene Contributes to Genetic Susceptibility of Aggressive Behavior Towards Others in Chinese Southwest Han Population

Cited by 34 publications

References 23 publications

The role of hypothalamus–pituitary–adrenal genes and childhood trauma in borderline personality disorder

The role of hypothalamus–pituitary–adrenal genes and childhood trauma in borderline personality disorder

The neurobiological basis of human aggression: A review on genetic and epigenetic mechanisms

Association of MTHFR, SLC19A1 Genetic Polymorphism, Serum Folate, Vitamin B12 and Hcy Status with Cognitive Functions in Chinese Adults

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