Search Results (18)

Genetic features of alcohol dependence have been extensively investigated in recent years. A large body of studies has underlined the important role of genetic variants not only in metabolic pathways but also in the neurobiology of alcohol dependence, mediated by the neuronal circuits regulating reward and craving. Serotonin transporter (5-HTT), encoded by the SLC6A4 gene (Solute carrier family 6-neurotransmitter transporter-member 4), is targeted by antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs) and plays a pivotal role in serotoninergic transmission; it has been associated with psychiatric diseases and alcohol dependence. Transcriptional regulation and expression of 5-HTT depend not only on epigenetic modifications, among which DNA methylation (CpG and non-CpG) is primarily involved, but also on sequence variations occurring in intron/exon regions and in untranslated regions in 5′ and 3′, being the first sequences important for the splicing machinery and the last for the binding of transcription factors and micro RNAs. This work intends to shed light on the role of sequence variations known to affect the expression or function of 5-HTT in alcohol-dependent individuals. We found a statistically significant difference in the allelic (p = 0.0083) and genotypic (p = 0.0151) frequencies of the tri-allelic polymorphism, with higher function alleles and genotypes more represented in the control population. Furthermore, we identified three haplotypes more frequent in subjects with AUD (p < 0.0001) and one more frequent in the control population (p < 0.0001). The results obtained for the tri-allelic polymorphism in alcohol dependence confirm what is already present in part of the literature. The role of haplotypes requires further studies to be clarified. Full article

ADHD is a neurodevelopmental disorder that children and adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls. We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p = 0.02 and p = 0.03, respectively), whereas the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p = 0.0002 and p = 0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highlighted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness, suggesting that these genotypes may be protective towards specific changes in behavior (p = 0.05). Interestingly, an increase in the GG genotype of rs6323 (p = 0.01) and a decrease in GT genotype (p = 0.0005) was also found in patients without aggressive behavior compared to controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help in the early detection of patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies. Full article

Yellow seed breeding is an effective method to improve oil yield and quality in rapeseed (Brassica napus L.). However, naturally occurring yellow-seeded genotypes have not been identified in B. napus. Mustard (Brassica juncea L.) has some natural, yellow-seeded germplasms, yet the molecular mechanism underlying this trait remains unclear. In this study, a BC₉ population derived from the cross of yellow seed mustard “Wuqi” and brown seed mustard “Wugong” was used to analyze the candidate genes controlling the yellow seed color of B. juncea. Subsequently, yellow-seeded (BY) and brown-seeded (BB) bulks were constructed in the BC₉ population and subjected to bulked segregant RNA sequencing (BSR-Seq). A total of 511 differentially expressed genes (DEGs) were identified between the brown and yellow seed bulks. Enrichment analysis revealed that these DEGs were involved in the phenylpropanoid biosynthetic process and flavonoid biosynthetic process, including key genes such as 4CL, C4H, LDOX/TT18, PAL1, PAL2, PAL4, TT10, TT12, TT4, TT8, BAN, DFR/TT3, F3H/TT6, TT19, and CHI/TT5. In addition, 111,540 credible single-nucleotide polymorphisms (SNPs) and 86,319 INDELs were obtained and used for quantitative trait locus (QTL) identification. Subsequently, two significant QTLs on chromosome A09, namely, qSCA09-3 and qSCA09-7, were identified by G’ analysis, and five DEGs (BjuA09PAL2, BjuA09TT5, BjuA09TT6, BjuA09TT4, BjuA09TT3) involved in the flavonoid pathway were identified as hub genes based on the protein-to-protein network. Among these five genes, only BjuA09PAL2 and BjuA09F3H had SNPs between BY and BB bulks. Interestingly, the majority of SNPs in BjuA09PAL2 were consistent with the SNPs identified between the high-quality assembled B. juncea reference genome “T84-66” (brown-seed) and “AU213” (yellow-seed). Therefore, BjuA09PAL2, which encodes phenylalanine lyase, was considered as the candidate gene associated with yellow seed color of B. juncea. The identification of a novel gene associated with the yellow seed coloration of B. juncea through this study may play a significant role in enhancing yellow seed breeding in rapeseed. Full article

Xishuangbanna (XIS) cucumber (Cucumis sativus L. var. xishuangbannanesis) is a semiwild variety originating from low latitude tropic areas, and therefore shows extreme cold sensitivity and heat tolerance. Here, we mapped the quantitative trait loci (QTLs) that control the cold sensitivity and heat tolerance of XIS cucumber seedlings. Using bulked segregant analysis (BSA), we identified three QTLs (HTT1.1, HTT3.1, and HTT3.2, with a total length of 11.98 Mb) for heat tolerance and two QTLs (LTT6.1 and LTT6.2, with a total length of 8.74 Mb) for cold sensitivity. The QTL LTT6.1 was then narrowed down to a length of 641 kb by using kompetitive allele-specific PCR (KASP) markers. Based on structural variants (SVs) and single-nucleotide polymorphisms (SNPs), we found the LTT6.1 is covered by a high divergent region including a 50 kb deletion in the XIS49 genome, which affects the gene structure of lipase abhydrolase domain containing 6 (ABHD6, Csa_6G032560). Accordingly, there is a very big difference in lipid composition, but not in other osmoprotectants like free amino acids and fatty acids, between XIS49 and cultivated cucumber CL. Moreover, we calculated the composite likelihood ratio (CLR) and identified selective sweeps from 115 resequencing data, and found that lipid- and fatty-acid-related processes are major aspects in the domestication of the XIS group cucumber. LTT6.1 is a particularly special region positioned nearby lipid-related selective sweeps. These studies above suggested that the lipid-related domestication of XIS cucumbers should account for their extreme cold sensitivity. Full article

Fear is characterized by distinct behavioral and physiological responses that are essential for the survival of the human species. Fear conditioning (FC) serves as a valuable model for studying the acquisition, extinction, and expression of fear. The serotonin (5-hydroxytryptamine, 5-HT) system is known to play a significant role in emotional and motivational aspects of human behavior, including fear learning and expression. Accumulating evidence from both animal and human studies suggests that brain regions involved in FC, such as the amygdala, hippocampus, and prefrontal cortex, possess a high density of 5-HT receptors, implicating the crucial involvement of serotonin in aversive learning. Additionally, studies exploring serotonin gene polymorphisms have indicated their potential influence on FC. Therefore, the objective of this work was to review the existing evidence linking 5-HT with fear learning and memory in humans. Through a comprehensive screening of the PubMed and Web of Science databases, 29 relevant studies were included in the final review. These studies investigated the relationship between serotonin and fear learning using drug manipulations or by studying 5-HT-related gene polymorphisms. The results suggest that elevated levels of 5-HT enhance aversive learning, indicating that the modulation of serotonin 5-HT2A receptors regulates the expression of fear responses in humans. Understanding the role of this neurochemical messenger in associative aversive learning can provide insights into psychiatric disorders such as anxiety and post-traumatic stress disorder (PTSD), among others. Full article

Background: Seeing that there are no data about associations between serotonin gene polymorphism and tryptophan catabolite concentration during PEG-IFN-α2a treatment, the aim of the current study is to examine (a) the associations between polymorphisms within the HTR1A, TPH2, and 5-HTT genes and the severity of depression symptoms and (b) the relationships among rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms and indoleamine 2,3-dioxygenase (IDO) activity, as well as kynurenine (KYN), tryptophan (TRP), kynurenic acid (KA), and anthranilic acid (AA) concentrations. Materials and methods: The study followed a prospective, longitudinal, single-center cohort design. The severity of the depressive symptoms of 101 adult patients with chronic HCV infections was measured during PEG-IFN-α2a/RBV treatment. We used the Montgomery–Åsberg Depression Rating Scale (MADRS) to assess the severity of depressive symptoms. The subjects were evaluated six times—at baseline and at weeks 2, 4, 8, 12, and 24. At all the time points, MADRS score, as well as KYN, TRP, KA, and AA concentrations, and IDO activity were measured. At baseline, rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms were assessed. Results: Subjects with C/C genotypes of 5-HT1A and lower-expressing alleles (S/S, L_G/L_G, and S/L_G) of 5-HTTLPR scored the highest total MADRS scores and recorded the highest increase in MADRS scores during treatment. We found associations between TRP concentrations and the TPH-2 and 5-HTTLPR rs25531 genotypes. Conclusions: Our findings provide new data that we believe can help better understand infection-induced depression as a distinct type of depression. Full article

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including GWAS. To develop an accurate test to help identify those at risk for at least Alcohol Use Disorder (AUD), Blum’s group developed the Genetic Addiction Risk Severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions published from 1990 until 2021. This analysis calculated the Hardy–Weinberg Equilibrium of each polymorphism in cases and controls. If available, the Pearson’s χ² test or Fisher’s exact test was applied to comparisons of the gender, genotype, and allele distribution. The statistical analyses found the OR, 95% CI for OR, and a post-risk for 8% estimation of the population’s alcoholism prevalence revealed a significant detection. The OR results showed significance for DRD2, DRD3, DRD4, DAT1, COMT, OPRM1, and 5HTT at 5%. While most of the research related to GARS is derived from our laboratory, we are encouraging more independent research to confirm our findings. Full article

Heat intolerance is the inability to withstand heat stress and this may occur due to exertional heat stroke (EHS). However, it is unknown if heat intolerance is associated with immune and hormonal disturbances. This study investigates haematological, biochemical and hormonal biomarkers related to heat intolerance and EHS in military and civilian volunteers. A quasi-experimental pre-and post-test design was used, with participants drawn from the Australian Defence Force (ADF) and the general populace. Blood samples were collected and analysed for biomarkers. Inferential statistics compared the biomarkers between the groups. Changes in alanine amino transaminase (p = 0.034), creatine kinase (0.044), cortisol (p = 0.041) and creatinine (p < 0.001) differed between the heat-intolerant and heat-tolerant groups. Participants with a history of EHS showed significant changes in creatinine (p = 0.022) and urea (p = 0.0031) compared to those without EHS history. Predictors of heat intolerance were increasing post-HTT creatinine and cortisol (OR = 1.177, p = 0.011 and OR = 1.015, p = 0.003 respectively). Conclusively, EHS history is associated with changes in creatinine and urea concentrations, while the predictors of heat intolerance are creatinine and cortisol. However, further exploration of other biomarkers, such as genetic polymorphism, is needed. Full article

It has been previously shown that the serotonin and dopamine neurotransmitter systems might influence the predisposition to suicidal behavior. This study aims to estimate the contribution of 11 polymorphisms in the genes SLC6A4 (5HTT), HTR1A, HTR2A, HTR1B, SLC6A3 (DAT1), DRD4, DRD2, COMT, and BDNF to suicidal behavior and severity of symptoms of depression and anxiety in the Russian population. The study was performed on 100 patients with repeated suicide attempts and 154 controls. We first found an association between SLC6A3 (DAT1) 40 bp VNTR locus and suicidal behavior. This association was significant; when using the codominant (p = 0.006), dominant (p = 0.001), overdominant (p = 0.004), and log-additive (p = 0.004) models, LL genotype played a protective role (OR = 0.48, 0.29–0.82, p = 0.005). Difference in the distribution of COMT rs4680 genotypes was significant in the codominant (p = 0.04), dominant (p = 0.013), and log-additive (p = 0.02) models, and AA genotype might protect against suicide (OR = 0.49, 0.26–0.91, p = 0.025). SLC6A4 5-HTTLPR + rs25531 locus was significant in the recessive model (p = 0.024), and also affected the severity of symptoms of depression (p = 0.044) and personal anxiety (p = 0.029). Our results suggest that allelic variants of SLC6A3, COMT, and SLC6A4 genes might be considered as risk factors for suicidal attempts. Full article

The genetic polymorphisms involved in the physiopathology of binge eating disorder (BED) are currently unclear. This systematic review aims to highlight and summarize the research on polymorphisms that is conducted in the BED. We looked for observational studies where there was a genetic comparison between adults with BED, in some cases also with obesity or overweight, and healthy controls or obesity/overweight without BED. Our protocol was written using PRISMA. It is registered at PROSPERO (identification: CRD42020198645). To identify potentially relevant documents, the following bibliographic databases were searched without a time limit, but until September 2020: PubMed, PsycINFO, Scopus, and Web of Science. In total, 21 articles were included in the qualitative analysis of the systematic review, as they met the eligibility criteria. Within the selected studies, 41 polymorphisms of 17 genes were assessed. Overall, this systematic review provides a list of potentially useful genetic polymorphisms involved in BED: 5-HTTLPR (5-HTT), Taq1A (ANKK1/DRD2), A118G (OPRM1), C957T (DRD2), rs2283265 (DRD2), Val158Met (COMT), rs6198 (GR), Val103Ile (MC4R), Ile251Leu (MC4R), rs6265 (BNDF), and Leu72Met (GHRL). It is important to emphasize that Taq1A is the polymorphism that showed, in two different research groups, the most significant association with BED. The remaining polymorphisms need further evidence to be confirmed. Full article

The expanded CAG repeat number in HTT gene causes Huntington disease (HD), which is a severe, dominant neurodegenerative illness. The accurate determination of the expanded allele size is crucial to confirm the genetic status in symptomatic and presymptomatic at-risk subjects and avoid genetic polymorphism-related false-negative diagnoses. Precise CAG repeat number determination is critical to discriminate the cutoff between unexpanded and intermediate mutable alleles (IAs, 27–35 CAG) as well as between IAs and pathological, low-penetrance alleles (i.e., 36–39 CAG repeats), and it is also critical to detect large repeat expansions causing pediatric HD variants. We analyzed the HTT-CAG repeat number of 14 DNA reference materials and of a DNA collection of 43 additional samples carrying unexpanded, IAs, low and complete penetrance alleles, including large (>60 repeats) and very large (>100 repeats) expansions using a novel triplet-primed PCR-based assay, the AmplideX PCR/CE HTT Kit. The results demonstrate that the method accurately genotypes both normal and expanded HTT-CAG repeat numbers and reveals previously undisclosed and very large CAG expansions >200 repeats. We also show that this technique can improve genetic test reliability and accuracy by detecting CAG expansions in samples with sequence variations within or adjacent to the repeat tract that cause allele drop-outs or inaccuracies using other PCR methods. Full article

Menopause is an important event in a woman’s life associated with hormonal changes that play a substantial role in the functioning of her body. A decline in the level of estrogens contributes to depressive symptoms and mood disorders during this period. The severity of depressive symptoms experienced by middle-aged women depends on many factors, including sociodemographic data (e.g., menopause, employment status, and marital status) and genetic variables (MAO-A and 5-HTT gene polymorphisms). In order to assess their influence on the development of depression in females, we analyzed 1453 healthy Polish women in different stages of menopause. Based on the results, we found that the l/l + l/s inheritance model for the 5-HTT gene polymorphism was more common in women without and with moderate depressive symptoms according to the Beck Depression Inventory (BDI), while the l/s model was more often observed in women with mild depression. Moreover, the overdominant 3/3 + 4/4 genotype of the MAO-A gene polymorphism was more often found in respondents without depressive symptoms, while women with depressive symptoms had more often the overdominant 3/4 genotype. Full article

The serotonin transporter (5-HTT in humans, SERT in rodents) is the main regulator of serotonergic transmission in the brain. The short allelic variant of the 5-HTT gene is in humans associated with psychopathologies and may enhance the vulnerability to develop depression after exposure to stressful events. Interestingly, the short allele also increases the sensitivity to a positive environment, which may buffer the vulnerability to depression. Since this polymorphism does not exist in rodents, male SERT knockout (SERT^−/−) rats were tested to explore the molecular mechanisms based on this increased predisposition. This article investigates the influences of a positive manipulation, namely, enriched environment (EE), on the depressive-like behavior observed in SERT^−/− rats. We found that one month of EE exposure normalized the anhedonic and anxious-like phenotype characteristics of this animal model. Moreover, we observed that EE exposure also restored the molecular alterations in the prefrontal cortex by positively modulating the expression of the neurotrophin Bdnf, and of spines and gamma-aminobutyric acid (GABA)ergic markers. Overall, our data confirm the depression-like phenotype of SERT^−/− rats and highlight the ability of EE to restore behavioral and molecular alterations, thus promoting the opportunity to use EE as a supporting non-pharmacological approach to treat mood disorders. Full article

Solid pseudopapillary tumor of the pancreas (SPT) is a rare pancreatic disease with a unique clinical manifestation. Although CTNNB1 gene mutations had been universally reported, genetic variation profiles of SPT are largely unidentified. We conducted whole exome sequencing in nine SPT patients to probe the SPT-specific insertions and deletions (indels) and single nucleotide polymorphisms (SNPs). In total, 54 SNPs and 41 indels of prominent variations were demonstrated through parallel exome sequencing. We detected that CTNNB1 mutations presented throughout all patients studied (100%), and a higher count of SNPs was particularly detected in patients with older age, larger tumor, and metastatic disease. By aggregating 95 detected variation events and viewing the interconnections among each of the genes with variations, CTNNB1 was identified as the core portion in the network, which might collaborate with other events such as variations of USP9X, EP400, HTT, MED12, and PKD1 to regulate tumorigenesis. Pathway analysis showed that the events involved in other cancers had the potential to influence the progression of the SNPs count. Our study revealed an insight into the variation of the gene encoding region underlying solid-pseudopapillary neoplasm tumorigenesis. The detection of these variations might partly reflect the potential molecular mechanism. Full article

The serotonergic system has been shown to be implicated in the regulation of mood and feeding behavior. Previous studies have identified a polymorphism in the 5′-flanking region of the serotonin transporter ( 5 - HTT ) gene of Lohmann Brown (LB) laying hens. The deleted variant D was found to be associated with increased body weight. The objective of this study was to address whether the increased body weight may be due to an increased feed intake. After hatching, hens were kept under ad libitum feeding conditions, and their body weight and feed intake were weekly determined. From 5 weeks of age, the body weight of hens with the D/D and W/D genotypes was significantly greater than that of W/W carrying hens. Interestingly, we found that the feed intake of D/D carrying hens, relative to body weight, was transiently increased only between 4 and 7 weeks of age ( p < 0.05), leading to a higher growth rate ( p < 0.05), compared with that of W/W carrying hens. These results suggest that the presence of variant D may be correlated with a transiently increased appetite of D/D carrying hens. Full article