CREB1 modulates the influence of childhood sexual abuse on adult's anger traits

Childhood maltreatment and genes underlie vulnerability to suicidal behaviours (SB), possibly by affecting the constitution of endophenotypes such as anger traits. The CREB protein has been implicated in antidepressant response, suicide and mood disorders in general. The aim of this study was to investigate if CREB1 gene is associated with SB and/or anger-related traits and if these associations are modulated by childhood maltreatment. Five hundred and thirty-four male suicide attempters and 357 male non-suicide attempters were genotyped for several polymorphisms within CREB1 gene. Four hundred and thirty-seven (156 non-suicide attempters and 281 suicide attempters) completed the State-Trait Anger Expression Inventory (STAXI) and 288 (265 suicide attempters and 23 controls) fulfilled the Childhood Trauma Questionnaire (CTQ). In total, 72 males had experienced childhood sexual abuse. Our results did not show any significant association between CREB1 and suicide behaviour. We found a significant interaction showing that CREB1 rs4675690 polymorphism modulated the effect of childhood sexual abuse on adulthood anger-out levels (P = 0.003). Sexually abused subjects carrying the CC genotype showed higher anger-out scores than T allele carriers, whereas no difference was observed in non-sexually abused subjects. CREB1 rs4675690 polymorphism modulates the association between childhood sexual abuse and adulthood anger-trait level. This is, to our knowledge, the first study to show such an interaction and to highlight the main effect of this gene on modulating the effect of child abuse on psychopathologies and warrant further investigation on this topic.     

Investigation of A218C tryptophan hydroxylase polymorphism: association with familial suicide behavior and proband's suicide attempt characteristics

According to WHO, suicide accounts for about 1 000 000 deaths worldwide every year. In view of these dramatic data, several studies have tried to identify possible biological mechanisms and markers of suicide. Genes encoding for proteins involved in the serotonergic transmission are major candidates in association studies of suicidal behavior. The gene that codes for tryptophan hydroxylase (TPH), the rate-limiting enzyme in the biosynthesis of serotonin, is one of these candidates. Two polymorphisms in intron 7 of this gene (A218C and A779C) have been described, but their role in suicidal behavior remains uncertain. TPH A218C polymorphism was analyzed in a sample of 248 psychiatric patients and 63 healthy controls. In addition, at least one close relative member was interviewed to assess family suicidal behavior history. Our research confirmed that a positive history of suicide attempts in a family member is associated with the chance of an individual to attempt suicide. Furthermore, we demonstrated that familial suicide attempts are more lethal and frequently more violent. We were not able to find significant differences of the TPH genotype frequencies between patients and controls. The TPH A218C genotypes were not associated with a history of suicide attempt and the lethality of the most lethal lifetime suicide attempt and suicide attempt method. The authors conclude that the A218C polymorphism of the TPH gene may not be a susceptibility factor for suicidal behavior in this group of psychiatric patients but confirm that a family suicidal behavior history increases the proband's suicide attempt risk.     

COMT but not serotonin‐related genes modulates the influence of childhood abuse on anger traits

Anger‐related traits are regulated by genes as well as early environmental factors. Both childhood maltreatment and genes underlie vulnerability to suicidal behaviors, possibly by affecting the constitution of intermediate phenotypes such as anger traits. The aim of this study was to test the interaction between nine candidate genes and childhood maltreatment in modulating anger‐related traits in 875 adult suicide attempters. The State‐Trait Anger Expression Inventory and the Childhood Trauma Questionnaire were used to examine anger traits and traumatic childhood experiences, respectively. The functional polymorphism of the catecholamine‐O‐methyl‐transferase (COMT) gene Val158Met significantly modulated the association between sexual abuse and anger‐trait level (P = 0.001). In the presence of sexual abuse, individuals carrying the Val high‐activity allele displayed greater disposition toward anger than individuals homozygous for the Met allele (P = 0.0003). Notably, none of the serotonin‐related genes influenced the effect of childhood abuse on anger traits. The results of the present study suggest that anger‐trait level is influenced by the interaction between childhood abuse and functional polymorphism in the COMT gene. This study was carried out in a population with a high frequency of childhood abuse and a high disposition toward anger, and replication in healthy subjects is needed.     

Polymorphism of the angiotensin II type 1 receptor in patients with essential hypertension in Ukrainian population

The distribution of polymorphism of the angiotensin II type 1 receptor in Ukrainian population was investigated. Healthy persons had genotypes AA (51%), AC (34%), CC (15%) and alleles A (68%), C (32%). We suppose the prevalence of allele C and genotypes CC in health persons in Ukrainian population. The frequencies of genotypes and alleles in patients with essential hypertension were AA (22,85%), AC (51,9%), CC (25,3%) and A (48,7%), C (51,3%). Thus the development of essential hypertension was associated with the presence of allele C and its homozygote variant. Moreover the severity and complications of hypertension depended on the presence of this allele and genotype. We concluded that Ukrainian population has specific distribution of polymorphism of the angiotensin II type 1 receptor with prevalence of allele C1166 and genotype CC. The presence of these genetic variants is a risk factor for essential hypertension.     

Personality Traits of Suicidality Are Associated with Premenstrual Syndrome and Premenstrual Dysphoric Disorder in a Suicidal Women Sample

Objective

Both Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD) might increase the risk of suicidal behavior. The aim of this study was to assess the relationship between personality dimensions specifically involved in suicidal vulnerability and PMS/PMDD.

Method

We collected data from 232 women consecutively hospitalized after a suicide attempt. We examined the relationship between impulsivity, aggressiveness/hostility, hopelessness, trait anger, affect intensity, emotional lability, and PMS/PMDD. Notably, we created an algorithm from the shortened Premenstrual Assessment form in order to assess PMDD status.

Results

The proportions of PMS and PMDD among female suicide attempters were 50% and 23% respectively. Women with PMS or PMDD were more likely to endorse most of these personality traits to than those without even after controlling for potential confounders. We found an impulsive-aggressive pattern of personality in women with PMS or PMDD, independently from the time of the menstrual cycle. Interestingly, trait anger remained associated with both PMS and PMDD independently of every other personality traits. The higher the anger level, the higher the risk was to suffer from both PMS and PMDD.

Conclusions

This study demonstrates a strong, independent association between PMS/PMDD and trait anger among a representative sample of female suicide attempters. It is of major interest for clinicians in view of addressing a substantial public health problem among women of reproductive age.     

Chronotype differences in suicidal behavior and impulsivity among suicide attempters

Morning- and evening-type individuals differ on a number of psychological and biological variables. There has been increasing interest in the relationship between chronotype and personality traits. The aim of this study was to investigate the relationship between impulsivity and chronotype in suicide attempters. Eighty-nine suicide attempters were included in the study, and systematic information on suicide attempts was recorded. The Morningness-Eveningness Questionnaire was applied to determine chronotype, and attempter impulsivity was measured by the total score of the Barratt Impulsiveness Scale. Significant differences between chronotype and impulsivity scores were found. Evening-type subjects reported significantly higher impulsivity scores than both neither- and morning-types. A significant association between chronotype and type of suicide attempt was detected. The largest proportion of violent suicide attempters were evening-type subjects. Violent suicide attempters also reported significantly higher impulsivity scores than nonviolent attempters. Previous studies have pointed out possible relations between eveningness and impulsivity. Current findings suggest that eveningness may be a risk factor for violent suicide attempts by increasing impulsivity.     

Early childhood sexual abuse increases suicidal intent

Childhood sexual abuse has been consistently associated with suicidal behavior. We studied suicide attempt features in depressed individuals sexually abused as children. On average, sexual abuse started before age 9. It frequently coexisted with physical abuse. Suicide attempters more often had personality disorders and had endured abuse for longer, but did not differ in terms of other clinical characteristics from non‐attempters. Earlier onset of sexual abuse and its duration were associated with more suicide attempts. However, when personality disorders were included in the regression model, only these disorders predicted number of attempts. The severity of sexual abuse and the coexistence of physical abuse were correlated with age at first suicide attempt. However, only severity of sexual abuse was marginally associated with age at first suicide attempt in the regression model. Finally, the earlier the age of onset of sexual abuse, the higher the intent, even after controlling for age, sex and personality disorders. This suggests that the characteristics of childhood sexual abuse, especially age of onset, should be considered when studying the risk for suicidal behavior in abused populations.     

Association between polymorphisms in the SLC27A1 gene and milk production traits in Chinese Holstein cattle

We assessed SLC27A1, a candidate gene for milk production traits in Chinese Holstein cattle. DNA was extracted from the blood of 48 top Chinese Holstein Cattle selected according to phenotypic character and mixed into DNA pool for SNP detection. We tested blood samples of these cattle for SNPs in exon 3 and the 3'-flanking region of the SLC27A1 gene by using polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) and DNA sequencing. We found 2 polymorphic sites: 112T>C, a synonymous mutation, in exon 3 (SNP(1)), and 64G>A in the 3'-UTR (SNP(2)). We also determined the genotypes of 330 Chinese Holstein cattle by using PCR-restriction fragment length polymorphism (RFLP). We found 3 genotypes each at SNP(1) (TT, TC, and CC) and SNP(2) (GG, GA, and AA). The association among the different genotypes at these 2 sites and milk production traits was analyzed using a least-squares procedure. The results showed that cows with genotype CC had higher milk yields than those with genotype TC (0.01 < p < 0.05). No significant difference was detected among the 3 SNP(2) genotypes in terms of milk production traits. Our results provide evidence that the C allele have potential effects on milk yield trait.     

Influence of Sex on Suicidal Phenotypes in Affective Disorder Patients with Traumatic Childhood Experiences

Objectives

In the current study, we aimed to investigate the impact of childhood trauma on suicidal behaviour phenotypes in a group of patients with diagnosed affective disorder (unipolar or bipolar affective disorder).

Patients and Methods

Patients with and without a history of childhood abuse, measured by Childhood Trauma Questionnaire (CTQ), were assessed to explore risks for suicidal behaviour (including suicide attempt, self-harm and non-suicidal self-injury). The tested sample consisted of 258 patients (111 males and 147 females, in-patients and out-patients at the Department of Psychiatry and Psychotherapy, Medical University of Vienna and University Hospital Tulln, Lower Austria). Psychiatric diagnoses were derived from the SCAN (Schedules for Clinical Assessment in Neuropsychiatry) interview. In addition, patients were administered the Lifetime Parasuicidal Count (LPC), Suicidal Behaviour Questionnaire (SBQ-R), and Viennese Suicide Risk Assessment Scale (VISURIAS) questionnaires.

Results

In contrast to male suicide attempters, female suicide attempters showed both significantly higher total CTQ scores (p<0.001), and higher CTQ subscores (emotional, physical and sexual abuse, as well as emotional and physical neglect) in comparison to the non-suicidal control group. Besides, females with a history of self-harming behaviour (including suicidal intention) and Non-Suicidal-Self Injury (NSSI) had significantly higher CTQ total scores (p<0.001) than the control group.

Conclusion

These findings suggest gender differences in suicidal behaviour after being exposed to childhood trauma.     

Retracted: Rs11655237 polymorphism of LINC00673 affects the prognosis of cervical cancer by interfering with the interaction between LINC00673 and microRNA-1231

Single-nucleotide polymorphism (SNP) in long noncoding RNAs (lncRNAs) is known to disrupt the binding between lncRNAs and microRNAs. In this paper, we aimed to explore the role of LINC00673 rs11655237 SNP in the survival of cervical cancer (CC). Real-time polymerase chain reaction and western-blot analysis were used to detect expressions of LINC00673 and microRNA-1231 (miR-1231) in CC patients with different rs11655237 SNP genotypes. And the expression of LINC00673, miR-1231, and IFNAR1 was measured in mice and cells treated with exosomes carrying GG, GA, and AA rs11655237 genotypes. Compared with patients carrying the rs11655237 A allele of LINC00673 rs11655237 SNP, patients carrying the G allele showed higher overall survival and higher miR-1231 expression. In addition, the expression of miR-1231 was the highest in patients carrying the GG genotype and the lowest in patients carrying the AA genotype. Furthermore, the exosomes carrying GG, GA, and AA genotypes of LINC00673 rs11655237 SNP reduced tumor growth in mice, while the inhibitory effect of rs11655237 A allele was much stronger than that of the rs11655237 G allele. Additionally, exosome treatment upregulated the expression of LINC000673 and IFNAR1 while downregulating the expression of miR-1231. Interestingly, the A allele of rs11655237 generated a binding site for miR-1231 and subsequently affected the expression of IFNAR1, a target gene of miR-1231 containing a miR-1231 binding site in its 3′-untranslated region. Cells transfected with exosomes carrying GG, GA, and AA genotypes of LINC00673 rs11655237 SNP achieved higher LINC000673 and IFNAR1 expression along with lower miR-1231 expression. Therefore, rs11655237 can be used as a prognostic biomarker for CC.     

Chronotype Differences in Suicidal Behavior and Impulsivity Among Suicide Attempters

Morning- and evening-type individuals differ on a number of psychological and biological variables. There has been increasing interest in the relationship between chronotype and personality traits. The aim of this study was to investigate the relationship between impulsivity and chronotype in suicide attempters. Eighty-nine suicide attempters were included in the study, and systematic information on suicide attempts was recorded. The Morningness-Eveningness Questionnaire was applied to determine chronotype, and attempter impulsivity was measured by the total score of the Barratt Impulsiveness Scale. Significant differences between chronotype and impulsivity scores were found. Evening-type subjects reported significantly higher impulsivity scores than both neither- and morning-types. A significant association between chronotype and type of suicide attempt was detected. The largest proportion of violent suicide attempters were evening-type subjects. Violent suicide attempters also reported significantly higher impulsivity scores than nonviolent attempters. Previous studies have pointed out possible relations between eveningness and impulsivity. Current findings suggest that eveningness may be a risk factor for violent suicide attempts by increasing impulsivity. (Author correspondence: dryavuzselvi@yahoo.com)     

The C1473G polymorphism in gene tph2 is the main factor mediating the genetically defined variability of tryptophan hydroxylase-2 activity in the mouse brain

Brain neurotransmitter serotonin is involved in the regulation of many physiological functions and types of behavior. The key enzyme of serotonin synthesis in the brain is tryptophan hydroxylase-2 (TPH-2). An association of the C1473G polymorphism in gene tph2 causing the replacement of Pro447 by Arg447 in TPH-2 molecule with enzyme activity in the mouse brain of 10 inbred strains was found. Association of the polymorphism with the TPH-2 activity in the brain of F2 hybrids between strains C57BL/6 and CC57BR was shown. The results indicate that the C1473G polymorphism in gene tph2 is the main factor determining the genetic defined variability of enzyme activity in the mouse brain.     

The association between endothelial lipase ?384A/C gene polymorphism and acute coronary syndrome in a Chinese population

Endothelial lipase (EL) is a novel member of the triglyceride (TG) lipase family. A growing body of evidence has indicated that EL gene polymorphism might contribute to the process of cardiovascular diseases. This study was aimed to reveal the potential relationship between EL -384A/C gene polymorphism and acute coronary syndrome (ACS) in a Chinese Han population. The subjects were composed of 320 ACS patients and 315 age- and gender- matched controls. We detected the EL -384A/C genotypes and allele frequencies by using polymerase chain reaction-restriction fragment length polymorphism analysis. There was significant difference in AA genotype and AC+CC genotype between ACS and control groups (P?=?0.014). The A allele frequency was significantly higher in ACS group than in control group (87.8 vs 83.8?%, P?=?0.041). The relationship between the variant and ACS remained significant after adjusting for current smoker, hypertension, diabetes mellitus, total cholesterol and TG (OR?=?0.682, 95?% CI?=?0.472-0.986). The levels of HDL and ApoA-I were significantly higher in AC+CC genotype than in AA genotype (HDL: 1.20?±?0.35 vs 1.11?±?0.29?mmol/L, P?=?0.001; ApoA-I: 1.14?±?0.25 vs 1.08?±?0.21?g/L, P?=?0.009). We found that the EL -384A/C gene polymorphism might be associated with ACS in Chinese Han population, suggesting that the variant might be involved in the pathogenesis of ACS.     

黄颡鱼MSTN基因多态性及其与生长性状的相关性分析

肌肉生长抑制素基因(Myostatin,MSTN)属于转化生长因子β家族,其主要功能是负向调控肌肉的生长发育。采用PCR-SSCP技术对黄颡鱼MSTN基因进行单核苷酸多态性检测和分型,并与其生长性状进行关联分析。结果表明,在第一内含子部分检测到1个缺失位点和2个突变位点(T1003del、G1022A和T1063G),基因型分别为:AA、AB、CC、CD和DD;在第三外显子部分检测到1个突变位点(T132C),基因型分别为:EE和EF。关联性分析表明,AA基因型个体的全长、体长、体高、体厚、头长和体重显著大于CD和DD基因型(P<0.05),AA基因型雌性个体的全长、体长、体高、体厚、头长、尾柄高、尾柄厚和体重也显著大于DD基因型(P<0.05)。由此推断,AA基因型是影响雌性黄颡鱼生长性状的有利基因型,DD基因型是影响雌性黄颡鱼生长性状的不利基因型,可以尝试利用这两个位点对雌性黄颡鱼进行标记辅助选育。     

The BCL2 -938C>A Promoter Polymorphism Is Associated with Risk for and Time to Aseptic Loosening of Total Hip Arthroplasty

Aseptic loosening is a major cause of revision surgery of total hip arthroplasty (THA). Only few host factors affecting aseptic loosening have been identified until now, although they are urgently needed to identify and possibly treat those patients at higher risk for aseptic loosening. To determine whether the functional single nucleotide polymorphism (SNP) c.-938C>A (rs2279115), located in the promoter region of the BCL2 gene has an impact on aseptic loosening of THA we genotyped and analyzed 234 patients suffering from aseptic loosening and 231 patients after primary THA. The polymorphism is associated with risk for aseptic loosening with the CC genotype at highest risk for aseptic loosening, Odds Ratio CC vs. AA 1.93, 95%CI 1.15–3.25, p = 0.013. In contrast, low risk AA genotype carriers that still developed aseptic loosening showed a significantly shorter time to aseptic loosening than patients carrying the C allele (p = 0.004). These results indicate that the BCL2 -938C>A polymorphism influences the occurrence and course of aseptic loosening and suggests this polymorphism as an interesting candidate for prospective studies and analyses in THA registers.     

Association of angiotensin II type-1 receptor A1166C gene polymorphism with the susceptibility of end-stage renal disease

Abstract

Association between angiotensin II type-1 receptor (AT1R) A1166C gene polymorphism and end-stage renal disease (ESRD) risk is still controversial. This meta-analysis was performed to evaluate the association of AT1R A1166C gene polymorphism with ESRD susceptibility. The search was performed in the databases of PubMed, Embase and Cochrane Library as of 1 May 2012, and the eligible investigations were recruited for this meta-analysis. Nineteen literatures were identified for the analysis of association between AT1R A1166C gene polymorphism and ESRD susceptibility. There was no association between AT1R A1166C gene polymorphism and ESRD susceptibility for overall populations, Caucasians, Asians and Turkish population. Interestingly, CC genotype was associated with a higher risk of ESRD in Africans (OR?=?3.36, 95% CI: 1.42–7.99, p?=?0.006). However, C allele and AA genotype were not associated with the ESRD risk in African population. In conclusion, CC genotype might be a risk factor for the ESRD susceptibility in African population. However, more case-control association investigations on larger, stratified populations are required in the future.     

Genetic variation in the hypothalamic-pituitary-adrenocortical axis regulatory factor, T-box 19, and the angry/hostility personality trait

Neurotic personality traits are important factors in several psychiatric disorders and suicidal behavior. Here, we have investigated the existence of potential relationships between neurotic personality traits and genetic variation. Non-suicidal parents derived from trios (suicide attempter and both parents) and non-suicidal volunteers, examined by the Neuroticism, Extraversion and Openness (NEO) Personality Inventory - Revised (NEO PI-R), were divided into screening and replication samples. The screening sample (n= 127) was used to select potential relationships between neurotic personality traits and genetic variation among 130 single nucleotide polymorphisms (SNPs). Screening (analysis of variance) with regard to the personality dimension neuroticism indicated potential relationships at three different loci. More detailed analysis of these three SNPs at NEO PI-R facet level indicated four potential relationships. T-test analysis in the replication sample (n= 617) was used to retest the relationships indicated during screening. One of those relationships was confirmed in the replication sample (P= 0.0052; Bonferroni correction), indicating that genetic variation at the human T-box 19 (TBX19) locus is related to the personality trait angry/hostility. Furthermore, using analysis of haplotypes among trios by transmission disequilibrium test and its extension, the family-based association test, overtransmission of a haplotype GAC at the TBX19 locus was associated with increased angry/hostility scores among suicide attempters (P= 0.009; Bonferroni correction). This is to our knowledge the first report on the association of the angry hostility personality trait with genetic variation at the TBX19 locus, an important regulator of the hypothalamic-pituitary-adrenocortical axis.     

Molecular characterization, polymorphism of the ACOX1 gene and association with ultrasound traits in Bos taurus

Acyl-coenzyme A oxidase 1 (ACOX1) is the first enzyme in peroxisomal fatty acid β-oxidation; it is rate-limiting and plays a key role in fatty acid metabolism and fat deposition. ACOX1 is an important candidate gene for meat quality selection through marker-assisted selection. Genomic structural analysis showed that bovine ACOX1 shares 86% identity with human ACOX1. Using PCR-SSCP technology, we discovered a single nucleotide polymorphism (SNP) (A1865C) in exon 13 of the ACOX1 gene. Allele frequencies of this SNP were investigated and evaluated with the χ(2) test in 641 cattle populations; only the Jiaxian red population was not in Hardy-Weinberg equilibrium. Gene heterozygosity, effective allele numbers and polymorphism information content of the bovine ACOX1 locus in seven populations varied from 0.2778 to 0.4954, 1.3846 to 1.9817 and 0.2392 to 0.3727, respectively. We also looked for a potential association of this SNP with ultrasound traits in 327 individuals and found a significant effect on ultrasound backfat thickness and ultrasound marbling score (P < 0.05). Meat quality traits were analyzed in another 71 Qinchuan individuals to determine associations with genotype. Animals with genotype AA had higher mean values of backfat thickness than those with genotypes AC and CC. A represents the base before mutation and C represents the base after mutation. We conclude that this SNP of the ACOX1 gene has potential as a genetic marker for meat quality traits in cattle reproduction and breeding.     

VEGF gene mRNA expression in patients with coronary artery disease

To assess the expression of vascular endothelium growth factor (VEGF) mRNA in unstimulated peripheral blood mononuclear cells of patients with and without coronary artery disease (CAD). We also studied whether the functional VEGF -2,578C/A polymorphism may influence the level of VEGF mRNA expression in individuals undergoing coronary angiography because chest pain. We assessed 50 consecutive patients with angiographically confirmed CAD (CAD+). Also, 50 consecutive individuals with normal coronary studies were included in the study for comparison. VEGF mRNA expression was examined using quantitative real-time PCR and genotyping for VEGF -2,578C/A was performed using ARMS-PCR technique. VEGF mRNA expression was significantly decreased in CAD+ patients when compared to CAD- individuals (p = 0.01). The frequency of VEGF -2578 allele C and genotype CC was increased in CAD+ patients. In this regard, homozygosity for the CC genotype was more commonly observed in CAD+ (30 %) than in those without CAD disease (18 %). However, the difference was slightly out of the range of significance (p = 0.1). In addition, a trend for reduction in the expression of VEGF mRNA was observed when patients carrying the VEGF -2,578AA genotype were compared with those VEGF -2,578AC heterozygous or those homozygous for the VEGF -2,578CC genotype. VEGF gene expression is decreased in individuals with CAD+ disease. The VEGF -2,578C/A polymorphism may influences the expression of VEGF.