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      Linking Y‐chromosomal short tandem repeat loci to human male impulsive aggression

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          Abstract

          Introduction

          Men are more susceptible to impulsive behavior than women. Epidemiological studies revealed that the impulsive aggressive behavior is affected by genetic factors, and the male‐specific Y chromosome plays an important role in this behavior. In this study, we investigated the association between the impulsive aggressive behavior and Y‐chromosomal short tandem repeats (Y‐ STRs) loci.

          Methods

          The collected biologic samples from 271 offenders with impulsive aggressive behavior and 492 healthy individuals without impulsive aggressive behavior were amplified by PowerPlex RY23 PCR System and the resultant products were separated by electrophoresis and further genotyped. Then, comparisons in allele and haplotype frequencies of the selected 22 Y‐ STRs were made in the two groups.

          Results

          Our results showed that there were significant differences in allele frequencies at DYS448 and DYS456 between offenders and controls ( p < .05). Univariate analysis further revealed significant frequency differences for alleles 18 and 22 at DYS448 (0.18 vs 0.27, compared to the controls, p = .003, OR=0.57,95% CI=0.39–0.82; 0.03 vs 0.01, compared to the controls, p = .003, OR=7.45, 95% CI=1.57–35.35, respectively) and for allele 17 at DYS456 (0.07 vs 0.14, compared to the controls, p = .006, OR=0.48, 95% CI =0.28–0.82) between two groups. Interestingly, the frequency of haploid haplotype 22‐15 on the DYS448‐ DYS456 ( DYS448‐ DYS456‐22‐15) was significantly higher in offenders than in controls (0.033 vs 0.004, compared to the control, p = .001, OR = 8.42, 95% CI =1.81–39.24). Moreover, there were no significant differences in allele frequencies of other Y‐ STRs loci between two groups. Furthermore, the unconditional logistic regression analysis confirmed that alleles 18 and 22 at DYS448 and allele 17 at DYS456 are associated with male impulsive aggression. However, the DYS448‐ DYS456‐22‐15 is less related to impulsive aggression.

          Conclusion

          Our results suggest a link between Y‐chromosomal allele types and male impulsive aggression.

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          Most cited references31

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          Neurobiology of aggression and violence.

          Acts of violence account for an estimated 1.43 million deaths worldwide annually. While violence can occur in many contexts, individual acts of aggression account for the majority of instances. In some individuals, repetitive acts of aggression are grounded in an underlying neurobiological susceptibility that is just beginning to be understood. The failure of "top-down" control systems in the prefrontal cortex to modulate aggressive acts that are triggered by anger provoking stimuli appears to play an important role. An imbalance between prefrontal regulatory influences and hyper-responsivity of the amygdala and other limbic regions involved in affective evaluation are implicated. Insufficient serotonergic facilitation of "top-down" control, excessive catecholaminergic stimulation, and subcortical imbalances of glutamatergic/gabaminergic systems as well as pathology in neuropeptide systems involved in the regulation of affiliative behavior may contribute to abnormalities in this circuitry. Thus, pharmacological interventions such as mood stabilizers, which dampen limbic irritability, or selective serotonin reuptake inhibitors (SSRIs), which may enhance "top-down" control, as well as psychosocial interventions to develop alternative coping skills and reinforce reflective delays may be therapeutic.
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            The human Y chromosome: an evolutionary marker comes of age.

            Until recently, the Y chromosome seemed to fulfil the role of juvenile delinquent among human chromosomes--rich in junk, poor in useful attributes, reluctant to socialize with its neighbours and with an inescapable tendency to degenerate. The availability of the near-complete chromosome sequence, plus many new polymorphisms, a highly resolved phylogeny and insights into its mutation processes, now provide new avenues for investigating human evolution. Y-chromosome research is growing up.
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              A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity.

              This study presents preliminary evidence of an association between polymorphic variation in the gene for monoamine oxidase-A (MAOA) and interindividual variability in aggressiveness, impulsivity and central nervous system (CNS) serotonergic responsivity. An apparently functional 30-bp VNTR in the promoter region of the X-chromosomal MAOA gene (MAOA-uVNTR), as well as a dinucleotide repeat in intron 2 (MAOA-CAn), was genotyped in a community sample of 110 men. All participants had completed standard interview and questionnaire measures of impulsivity, hostility and lifetime aggression history; in a majority of subjects (n=75), central serotonergic activity was also assessed by neuropsychopharmacologic challenge (prolactin response to fenfluramine hydrochloride). The four repeat variants of the MAOA-uVNTR polymorphism were grouped for analysis (alleles '1+ 4' vs. '2+3') based on prior evidence of enhanced transcriptional activity in MAOA promoter constructs with alleles 2 and 3 (repeats of intermediate length). Men in the 1/4 allele group scored significantly lower on a composite measure of dispositional aggressiveness and impulsivity (P<0.015) and showed more pronounced CNS serotonergic responsivity (P<0.02) than men in the 2/3 allele group. These associations were also significant on comparison of the more prevalent one and three alleles alone (encompassing 93% of subjects). Although in linkage disequilibrium with the MAOA-uVNTR polymorphism, MAOA-CAn repeat length variation did not vary significantly with respect to behavior or fenflluramine challenge in this sample. We conclude that the MAOA-uVNTR regulatory polymorphism may contribute, in part, to individual differences in both CNS serotonergic responsivity and personality traits germane to impulse control and antagonistic behavior.
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                Author and article information

                Contributors
                hippocampus2007@gmail.com
                Journal
                Brain Behav
                Brain Behav
                10.1002/(ISSN)2157-9032
                BRB3
                Brain and Behavior
                John Wiley and Sons Inc. (Hoboken )
                2162-3279
                16 October 2017
                November 2017
                : 7
                : 11 ( doiID: 10.1002/brb3.2017.7.issue-11 )
                : e00855
                Affiliations
                [ 1 ] Department of Psychiatry Psychiatry Center of Chinese People's Liberation Army No.102 Hospital of People's Liberation Army Changzhou China
                [ 2 ] DNA Laboratory Public Security Bureau of Changzhou Changzhou China
                [ 3 ] Department of Neurology Laboratory of Neurological Diseases Changzhou No.2 People's Hospital The Affiliated Hospital of Nanjing Medical University Changzhou China
                Author notes
                [*] [* ] Correspondence

                Xianju Zhou, Department of Neurology, Laboratory of Neurological Diseases, Changzhou NO.2 People's Hospital The affiliated Hospital of Nanjing Medical University, Changzhou, China.

                Email: hippocampus2007@ 123456gmail.com

                [†]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0003-1744-556X
                Article
                BRB3855
                10.1002/brb3.855
                5698871
                5f627b49-6ce0-4915-9b04-fbfe75b6c996
                © 2017 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 June 2016
                : 13 April 2017
                : 17 September 2017
                Page count
                Figures: 0, Tables: 6, Pages: 8, Words: 6357
                Funding
                Funded by: Nanjing Military Region, the Ministry of Health Science and Technology Innovation programs
                Award ID: 09 MB113 and 13MS016
                Funded by: Changzhou Sci &Tech Program
                Award ID: CE20145045
                Funded by: Changzhou High‐Level Medical Talents Training Project
                Award ID: No. 2016CZLJ018
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                brb3855
                November 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.6 mode:remove_FC converted:22.11.2017

                Neurosciences
                allele,behavior,genetics,haploid,haplotype,impulsive aggression,male,offender,polymorphisms,short tandem repeats,y chromosome

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