Alma Genis

The role of brain‐derived neurotrophic factor (BDNF) Val66Met genetic polymorphism in bipolar disorder: a case–control study, comorbidities, and meta‐analysis of 16,786 subjects

The aim of this study was to evaluate the association of Val66Met brain‐derived neurotrophic factor (BDNF) polymorphism with bipolar disorder in (i) a meta‐analysis and (ii) a case–control study in a Mexican population. We also investigated the possible association of this polymorphism with clinical features.

Association of the 5HTR2A gene with suicidal behavior: CASE-control study and updated meta-analysis

BackgroundThe polymorphism rs6313 (T102C) has been associated with suicidal behavior in case–control and meta-analysis studies, but results and conclusions remain controversial. The aim of the present study was to examine the association between T102C with suicidal behavior in a case–control study and, to assess the combined evidence – this case–control study and available data from other related studies – we carried out a meta-analysis.MethodsWe conducted a case–control study that included 161 patients with suicide attempts and 244 controls; we then performed a meta-analysis. The following models were evaluated in the meta-analysis: A) C allele vs T allele; B) T allele vs C allele; C) Caucasian population, D) Asian population, and E) suicide attempters with schizophrenia.ResultsWe found an association between attempted suicide and control participants for genotype (χ2=6.28, p=0.04, df=2) and allele (χ2=6.17, p=0.01, df=1, OR 1.48 95% IC: 1.08-2.03) frequencies in the case–control study. The meta-analysis, comprising 23 association studies (including the present one), showed that the rs6313 polymorphism is not associated with suicidal behavior for the following comparisons:T allele vs C allele (OR: 1.03; 95% CI 0.93-1.13; p(Z)=0.44); C allele vs T allele: (OR:0.99; 95% CI: 0.90-1.08; p(Z)=0.22); Caucasians (OR:1.09; 95% CI: 0.96-1.23), and Asians (OR:0.96; 95% CI: 0.84-1.09).ConclusionOur results showed association between the rs6313 (T102C) polymorphism and suicidal behavior in the case–control study. However, the meta-analysis showed no evidence of association. Therefore, more studies are necessary to determine conclusively an association between T102C and suicidal behavior.

Association of 5HTR1A gene variants with suicidal behavior: Case-control study and updated meta-analysis

INTRODUCTION The gene encoding the serotonin 1A receptor (5HTR1A) has been a candidate gene associated with suicidal behavior in case-control and meta-analysis studies. We carried out a meta-analysis and a case-control study on the 5HTR1A gene to examine the association of this gene with suicidal behavior. METHODS We performed a systematic search in electronic databases to study meta-analytically the association of 5HTR1A gene with suicidal behavior; we found 9 published genetic association studies concerning the rs6295 polymorphism. To get a comprehensive knowledge of this association we conducted a case-control study on the following polymorphisms: rs1423691, rs6295, and rs878567 in a Mexican population; the sample was composed of 152 suicide attempters and 264 healthy subjects. RESULTS The meta-analysis revealed that the rs6295 polymorphism is not associated with suicidal behavior. Similarly, no significant association for polymorphisms rs6295 and rs878567 was found in the case-control study. The polymorphism rs1423691 was excluded of the association analysis because cases and control groups were in Hardy-Weinberg disequilibrium. CONCLUSION The meta-analysis of functional rs6295 polymorphisms produced no association. Likewise, the analysis in our case-control study in a Mexican population resulted in lack of association of polymorphisms rs6295 and rs878567 with suicidal behavior. However, further studies assessing different populations, as well as larger samples are necessary to obtain conclusive outcomes.

Study on genes of the serotonergic system and suicidal behavior: protocol for a case-control study in Mexican population.

BackgroundSuicidal behavior is a leading cause of injury and death worldwide. Several studies have provided a possible relationship between genetic factors and suicidal behavior. Also, these studies have shown evidence for altered serotonergic neural transmission in the pathogenesis of suicidal behavior. In addition, genes pertaining to the serotonergic system have been proposed as candidates to establish biological correlates between suicidal behavior and the serotonergic system. The most studied genes are SCL6A4, HTR2A, HTR2C, HTR1A, HTR1B, TPH-1, and TPH-2. To get a comprehensive understanding of the association with suicidal behavior we will conduct genotype assays studies in a Mexican population.Methods/DesignWe will conduct a case–control study. The population sample will comprise adolescent and adult patients admitted for attempted of suicide and diagnosed by a psychiatrist. A peripheral blood sample will be taken from all the subjects (cases and controls). Genomic DNA from the leukocytes blood sample will be extracted. The genotypes of interest are distributed in the following genes: SCL6A4, HTR2A, HTR1A, HTR1B, HTR2C, TPH-2 and TPH-1. All the samples will be analyzed using a polymerase chain reaction (PCR) end-point method. We will evaluate the Hardy-Weinberg Equilibrium. The chi-squared test or Fisher’s exact test will be used to compare genotype and allele frequencies between control and case groups. The Quanto 1.2 software will measure the sample size of the association. For all the association analyses the level of significance will be set at p = 0.05 and the confidence interval at 95%.DiscussionSuicidal behavior has been increase in Mexico, principally in young population. Our study will demonstrate the association between serotoninergic genes and suicide behavior in Mexican population.

Distribution of the Val108/158Met polymorphism of the COMT gene in healthy Mexican population☆

Catechol-O-methyltransferase (COMT) inactivates the catecholamines adrenaline, noradrenaline and dopamine. On the other hand, some studies have reported that the enzymatic activity of COMT is partly genetically determined. With regard to the COMT gene, the most studied polymorphism is the functional variant Val108/158Met (rs4680), which results in substantial three- to four-fold variations in enzyme activity. To date, the rs4680 polymorphism of COMT has been associated with a number of disorders. In addition, this polymorphism has been found to have important differences in frequency according to the studied population. Therefore, the aim of the present study was to evaluate the frequency of a common single nucleotide polymorphism (SNP) Val108/158Met of the COMT gene in the Mexican population. Accordingly, we recruited 431 healthy volunteers. Our sample consisted of 111 healthy individuals from Mexico City and 320 individuals from the state of Tabasco, Mexico. We observed that Met was the most common allele, ranging from 57% (Tabasco) to 85% (Mexico City). In addition, we analyzed the frequency of Val108/158Met polymorphism of Caucasian (54% Met allele), Asian (29% Met allele) and African (34% Met allele) populations separately and also in comparison with Mexican (63% Met allele) population. In conclusion, the distribution of the Val108/158Met polymorphism distinguishes the Mexican population studied from other populations, but it is necessary to increase the size of the sample to get more conclusive results.

No association between ApoE and schizophrenia: Evidence of systematic review and updated meta-analysis

INTRODUCTION Schizophrenia affects between 0.3% and 2% of the worldwide population. A genetic contribution has been postulated in the development of this disorder. Genes such as ApoE have been implicated in the neurodevelopment associated with schizophrenia in case-control and meta-analysis studies, but the results remain inconclusive. Due to this, the aim of the present study was to explore the association between ApoE and schizophrenia through a meta-analysis. MATERIAL AND METHODS We collected all relevant studies by searching PubMed and EBSCO databases. The pooled odds ratios with 95% confidence intervals were calculated to estimate the association. The following models were evaluated: A) ε4 vs ε3, B) ε4 vs ε2, C) ε4 vs ε3+ε2, D) Caucasian population and E) Asian population. Statistical analyses were performed using EPIDAT 3.1 software. RESULTS The meta-analyses comprised 28 association studies, which included 4703 controls and 3452 subjects with schizophrenia. A significant protective effect was found for allele ε3 in the Asian population (OR=0.73, 95% CI=0.54-0.98). No significant associations were observed in the other models and populations analyzed. CONCLUSIONS Our meta-analysis suggests a protective association between ApoE allele ε3 and schizophrenia in the Asian population.

Association analysis of TPH-1 and TPH-2 genes with suicidal behavior in patients with attempted suicide in Mexican population

BACKGROUND Suicidal behavior is a worldwide health problem. Tryptophan hydroxylase (TPH) is a rate limiting enzyme in the biosynthesis of serotonergic neurotransmission. TPH-1 and TPH-2 genes encode for TPH isoforms and have been implicated as candidate genes for suicidal behavior. The aim of this study was to evaluate the association between the genetic variants of the TPH-1 (rs21102 and 1607395) and TPH-2 (rs4290270, rs7305115 and rs1007023) genes and suicidal behavior in a Mexican population. METHODS We conducted a case-control study including 200 cases with suicide attempt and 263 controls. Patients were evaluated by a trained psychiatrist or clinical psychologists. Five polymorphisms were genotyped and assessed for allele, genotype and haplotype association with suicide attempt. RESULTS The rs7305115 polymorphism of the TPH-2 gene was associated with suicidal behavior in a Mexican population in genotype (χ(2)=6.02, df=2, p=0.04) and allele (OR=1.39, 95%IC=1.06-1.81, p=0.01) frequencies. The THP-2 haplotypes GTA (χ(2)=5.68, p=0.01) and ATT (χ(2)=5.0, p=0.02) were associated with risk for suicide attempt. CONCLUSION Our results provide evidence for an association between the rs7305115 polymorphism of the TPH-2 gene and suicidal behavior in a Mexican population. However, more studies are necessary to replicate these results using larger samples.

Gender differences in the association between HTR2C gene variants and suicidal behavior in a Mexican population: a case–control study

Background The aim of this case–control study was to explore the association by gender between the HTR2C gene variants and suicidal behavior in a Mexican population. Subjects and methods A total of 183 suicide attempters and 208 healthy volunteers were included in this study. We genotyped five polymorphisms of HTR2C (rs547536, rs2192372, rs4272555, rs6318, and rs2428707), then measured the association by genotype, allele, and haplotype. Results In the female group, we found an association between two polymorphisms of the HTR2C (rs4272555 and rs2428707) and suicide attempts. The C allele of the single-nucleotide polymorphism (SNP) rs4272555 was associated with a decreased risk of suicide attempt (P=0.01, odds ratio =0.26, 95% confidence interval: 0.09–0.79), whereas the G allele of the SNP rs2428707 was associated with an increased risk of suicide attempt (P=0.01, odds ratio =3.68, 95% confidence interval: 1.24–10.90). No significant association was observed between the other polymorphisms studied (rs547536, rs2192372, rs6318) or haplotypes with suicide attempts. Conclusion These findings suggest a possible risk factor of the HTR2C gene in the pathology of suicidal behavior in Mexican population. More studies are necessary to confirm this association.

Association between the SAT-1 Gene and Suicidal Behavior in Mexican Population

Objective: The gene coding for spermidine/spermine N1-acetyltransferase 1 (SAT-1) participates in the metabolic pathways of polyamines as a rate-limiting enzyme; this gene is involved in regulating polyamine levels and it has been considered a candidate gene for suicidal behavior. The aim of this study was to determine the association between SAT-1 polymorphism A-1537C (rs6526342) and suicidal behavior, in a sample of suicide attempt patients in the Mexican population. Methods: To observe the association between rs6526342 and suicidal behavior, we evaluated 169 unrelated suicide attempters and compared them to 218 non-suicidal individuals. Patients were evaluated by a trained psychiatrist or clinical psychologist. SAT-1 rs6526342 genotypes were analyzed using the polymerase chain reaction end-point method. Results: No significant association was observed between cases and comparison group for allele frequency (p=0.40, df=1, p=0.69). However, a significant association between rs6526342 and suicidal behavior was observed in the male group for allele distribution (χ2=4.0, df=1, p=0.04, OR 0.48; 95% CI: 0.24-0.98), whereas in the female group, no association was found by genotype (χ2= 2.85, df=2, p=0.23) or allele (χ2=0.01, df=1, p=0.91) frequency. Conclusion: Our results showed an association between allele C of the polymorphism in the promoter region of SAT-1 A-1537C (rs6526342) and suicidal behavior in Mexican males. This suggests that the SAT-1 gene may contribute to the risk for suicidal behavior among the Mexican population.

Potential drug–drug interaction in Mexican patients with schizophrenia

Abstract Objective: The aim of this study was to observe potential drug–drug interactions in the medication of Mexican schizophrenic patients. Methods: We performed a retrospective and cross-sectional study that was carried out in a psychiatric clinic. Only the prescriptions of patients with schizophrenia whose diagnoses were based on the DSM-IV instrument were included in this study. The Drug Interactions Checker software (http://www.drugs.com/drug_interactions.html) was used in this study to analyse potential drug–drug interactions. Results: In total, 86 of 126 patients were at risk of potential drug–drug interactions. Haloperidol and biperiden was the most common drug pair of 232 pairs evaluated. In our study, 13.8% of drug–drug interaction showed a major level of severity, whereas in 83.2%, the interaction was moderate. Finally, central nervous system (CNS) depression and anticholinergic effect were the main possible effects of drug–drug interaction. Conclusions: Our results revealed a high number of patients with schizophrenia receiving two or more drugs. The potential drug–drug interactions observed in the Mexican population are consistent with the concomitant use of antipsychotics, benzodiazepines, and antidepressants prescribed in schizophrenia that could cause central nervous system (CNS) depression and anticholinergic effect. Drug–drug interaction must be considered when the patient with schizophrenia is medicated.