Polymorphic Region Research Articles

Leveraging epigenomes and three-dimensional genome organization for interpreting regulatory variation.

Understanding the impact of regulatory variants on complex phenotypes is a significant challenge because the genes and pathways that are targeted by such variants and the cell type context in which regulatory variants operate are typically unknown. Cell-type-specific long-range regulatory interactions that occur between a distal regulatory sequence and a gene offer a powerful framework for examining the impact of regulatory variants on complex phenotypes. However, high-resolution maps of such long-range interactions are available only for a handful of cell types. Furthermore, identifying specific gene subnetworks or pathways that are targeted by a set of variants is a significant challenge. We have developed L-HiC-Reg, a Random Forests regression method to predict high-resolution contact counts in new cell types, and a network-based framework to identify candidate cell-type-specific gene networks targeted by a set of variants from a genome-wide association study (GWAS). We applied our approach to predict interactions in 55 Roadmap Epigenomics Mapping Consortium cell types, which we used to interpret regulatory single nucleotide polymorphisms (SNPs) in the NHGRI-EBI GWAS catalogue. Using our approach, we performed an in-depth characterization of fifteen different phenotypes including schizophrenia, coronary artery disease (CAD) and Crohn's disease. We found differentially wired subnetworks consisting of known as well as novel gene targets of regulatory SNPs. Taken together, our compendium of interactions and the associated network-based analysis pipeline leverages long-range regulatory interactions to examine the context-specific impact of regulatory variation in complex phenotypes.

Influences of neurotransmission-related genetic polymorphisms on depression, anxiety and stress

Over 10% of the world population suffer from mental disorders. In particular, depression causes about 800,000 suicide cases annually, while anxiety is the most common mental disorder. Stresses from work, life, and health have been identified as the common triggers for the two mental disorders. Eventhough mental disorders are treatable and validated tools are available to diagnose, many individuals are left untreated due to different factors, such as a lack of trained personnel and stigma. Neuroscience research indicates that mental disorders could be hereditary, where genes involved in determining behavioural variants. Disturbance in brain communication, resulting from abnormalities in neurogenesis, neurotransmission, and enzymatic degradation, have led to negative emotional states. This mini-review will highlight some important genes in the neurotransmitter systems and explore the relationship between gene polymorphisms and emotional states (i.e., depression, anxiety, and stress). The genes that will be discussed in this mini-review include brain-derived neurotrophic factor (BDNF) which is involved in neuron development, serotonin-transporter-linked polymorphic region (5-HTTLPR) and 5-hydroxytryptamine receptor 1A (5-HT1A) which are involved in serotonin neurotransmitter action potential propagation, and monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT), which are involved in neurotransmitter catabolism.

Role of the HLA-G regulatory region polymorphisms in idiopathic recurrent spontaneous abortions (RSA).

HLA-G polymorphisms have a functional impact on its expression and may cause a breakdown of maternal tolerance towards the semi-allogenic fetus, resulting in recurrent spontaneous abortions (RSA). This study reports on the association of HLA-G regulatory region polymorphisms with idiopathic RSA. Seventy-five couples with ≥2 spontaneous abortions were recruited in comparison to 75 healthy couples who had normal pregnancies. About 5mL of blood samples were collected from all the participants, and DNA was extracted. Screening of HLA-G 5'-upstream regulatory region (5'-URR) was done by direct sequencing in 50 each of RSA and healthy couples, respectively. The 14bp deletion/insertion polymorphism in the 3'-untranslated region (3'-UTR) was genotyped in 75 each of RSA and healthy couples, respectively, by PCR amplification of HLA-G exon 8. MedCalc, GraphPad Prism, Haploview, PLINK, and multifactor dimensionality reduction were used to analyze the data. HLA-G screening revealed the presence of -762C/T, -725C/G, -716T/G, -689A/G, -486C/A, and -477C/G single nucleotide polymorphisms (SNPs) in the 5'-URR. At positions -762 and -477, the frequency of CC homozygotes was significantly higher in controls compared to the patients. The 14bp deletion/insertion polymorphism in the 3'-UTR showed an association with RSA with the heterozygous genotype being significantly higher in RSA compared to controls. The study indicates a protective role of the CC genotypes of the two HLA-G 5'-URR polymorphisms, -762C/T and -477C/G, against RSA. It also suggests that women with the 14bp deletion/insertion genotype have a significantly higher risk of RSA.

Complimentary electrostatics dominate T-cell receptor binding to a psoriasis-associated peptide antigen presented by human leukocyte antigen C∗06:02

Psoriasis is a chronic skin disease characterized by hyperproliferative epidermal lesions infiltrated by autoreactive T cells. Individuals expressing the human leukocyte antigen (HLA) C∗06:02 allele are at highest risk for developing psoriasis. An autoreactive T cell clone (termed Vα3S1/Vβ13S1) isolated from psoriatic plaques is selective for HLA-C∗06:02, presenting a peptide derived from the melanocyte-specific autoantigen ADAMTSL5 (VRSRRCLRL). Here we determine the crystal structure of this psoriatic TCR-HLA-C∗06:02 ADAMTSL5 complex with a stabilized peptide. Docking of the TCR involves an extensive complementary charge network formed between negatively charged TCR residues interleaving with exposed arginine residues from the self-peptide and the HLA-C∗06:02 α1 helix. We probed these interactions through mutagenesis and activation assays. The charged interface spans the polymorphic region of the C1/C2 HLA group. Notably the peptide-binding groove of HLA-C∗06:02 appears exquisitely suited for presenting highly charged Arg-rich epitopes recognized by this acidic psoriatic TCR. Overall, we provide a structural basis for understanding the engagement of melanocyte antigen-presenting cells by a TCR implicated in psoriasis while simultaneously expanding our knowledge of how TCRs engage HLA-C.

Association of HLA diversity with the risk of 25 cancers in the UK Biobank.

The human leukocyte antigen (HLA) is a highly polymorphic region, and HLA diversity may play a role in presenting tumour-associated peptides and inducing immune responses. However, the effect of HLA diversity on cancers has not been fully assessed. We aimed to explore the role of HLA diversity on cancer development. A pan-cancer analysis was performed to evaluate the effect of HLA diversity, measured by HLA heterozygosity and HLA evolutionary divergence (HED), on the susceptibility of 25 cancers in the UK Biobank. We observed that the diversity of HLA class II locus was associated with a lower risk of lung cancer (ORhetero=0.94, 95% CI= 0.90-0.97, P= 1.29×10-4) and head and neck cancer (ORhetero=0.91, 95% CI= 0.86-0.96, P=1.56×10-3). Besides, a lower risk of non-Hodgkin lymphoma was associated with an increased diversity of HLA class I (ORhetero=0.92, 95% CI= 0.87-0.98, P=8.38×10-3) and class II locus (ORhetero=0.89, 95% CI= 0.86-0.92, P= 1.65×10-10). A lower risk of Hodgkin lymphoma was associated with the HLA class I diversity (ORhetero=0.85, 95% CI= 0.75-0.96, P= 0.011). The protective effect of HLA diversity was mainly observed in pathological subtypes with higher tumour mutation burden, such as lung squamous cell carcinoma (P= 9.39×10-3) and diffuse large B cell lymphoma (Pclass I= 4.12×10-4; Pclass Ⅱ= 4.71×10-5), as well as the smoking subgroups of lung cancer (P= 7.45×10-5) and head and neck cancer (P= 4.55×10-3). We provided a systematic insight into the effect of HLA diversity on cancers, which might help to understand the etiological role of HLA on cancer development. This study was supported by grants from the National Natural Science Foundation of China (82273705, 82003520); the Basic and Applied Basic Research Foundation of Guangdong Province, China (2021B1515420007); the Science and Technology Planning Project of Guangzhou, China (201804020094); Sino-Sweden Joint Research Programme (81861138006); the National Natural Science Foundation of China (81973131, 81903395, 81803319, 81802708).

Genomic diversity of mpox virus in Paris area (France) during the 2022 outbreak.

In May 2022, several countries reported mpox cases from patients without history of traveling to endemic areas. France was one of the most affected European countries by this outbreak. In this study, the clinical characteristics of mpox cases in France were described, and the genetic diversity of the virus was studied. Patients diagnosed with mpox infection (quantitative polymerase chain reaction ct < 28) between May 21, and July 4, 2022 and between 16th August and 10th September 2022 were included to this study. Twelve amplicons corresponding to the most polymorphic regions of the mpox genome and covering ~30 000 nucleotides were generated and sequenced using the S5 XL Ion Torrent technology to evaluate the genetic diversity of mpox sequences. One hundred and forty-eight patients were diagnosed with mpox-infection. 95% were men, 5% transgender (M-to-F), 50% were taking human immunodeficiency virus (HIV) pre-exposure prophylaxis, and 25% were HIV seropositive. One hundred and sixty-two samples (some patients had two samples) were sequenced and compared to GenBank sequences. Overall, low genetic diversity of mpox sequences was found compared with pre-epidemic Western-African sequences, with 32 distinct mutational patterns. This study provides a first glance at the mutational landscape of early mpox 2022 circulating strains in Paris (France).

Rapid evolutionary change, constraints and the maintenance of polymorphism in natural populations of Drosophila melanogaster.

Allele frequencies can shift rapidly within natural populations. Under certain conditions, repeated rapid allele frequency shifts can lead to the long-term maintenance of polymorphism. In recent years, studies of the model insect Drosophila melanogaster have suggested that this phenomenon is more common than previously believed and is often driven by some form of balancing selection, such as temporally fluctuating or sexually antagonistic selection. Here we discuss some of the general insights into rapid evolutionary change revealed by large-scale population genomic studies, as well as the functional and mechanistic causes of rapid adaptation uncovered by single-gene studies. As an example of the latter, we consider a regulatory polymorphism of the D. melanogaster fezzik gene. Polymorphism at this site has been maintained at intermediate frequency over an extended period of time. Regular observations from a single population over a period of 7 years revealed significant differences in the frequency of the derived allele and its variance across collections between the sexes. These patterns are highly unlikely to arise from genetic drift alone or from the action of sexually antagonistic or temporally fluctuating selection individually. Instead, the joint action of sexually antagonistic and temporally fluctuating selection can best explain the observed rapid and repeated allele frequency shifts. Temporal studies such as those reviewed here further our understanding of how rapid changes in selection can lead to the long-term maintenance of polymorphism as well as improve our knowledge of the forces driving and limiting adaptation in nature.

Genetic predisposition to neuroblastoma results from a regulatory polymorphism that promotes the adrenergic cell state.

Childhood neuroblastomas exhibit plasticity between an undifferentiated neural crest-like mesenchymal cell state and a more differentiated sympathetic adrenergic cell state. These cell states are governed by autoregulatory transcriptional loops called core regulatory circuitries (CRCs), which drive the early development of sympathetic neuronal progenitors from migratory neural crest cells during embryogenesis. The adrenergic cell identity of neuroblastoma requires LMO1 as a transcriptional cofactor. Both LMO1 expression levels and the risk of developing neuroblastoma in children are associated with a single nucleotide polymorphism, G/T, that affects a GATA motif in the first intron of LMO1. Here, we showed that WT zebrafish with the GATA genotype developed adrenergic neuroblastoma, while knock-in of the protective TATA allele at this locus reduced the penetrance of MYCN-driven tumors, which were restricted to the mesenchymal cell state. Whole genome sequencing of childhood neuroblastomas demonstrated that TATA/TATA tumors also exhibited a mesenchymal cell state and were low risk at diagnosis. Thus, conversion of the regulatory GATA to a TATA allele in the first intron of LMO1 reduced the neuroblastoma-initiation rate by preventing formation of the adrenergic cell state. This mechanism was conserved over 400 million years of evolution, separating zebrafish and humans.

P53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act.

Doxorubicin (DOX) is a highly effective chemotherapeutic drug, but its long-term use can cause cardiotoxicity and drug resistance. Accumulating evidence demonstrates that p53 is directly involved in DOX toxicity and resistance. One of the primary causes for DOX resistance is the mutation or inactivation of p53. Moreover, because the non-specific activation of p53 caused by DOX can kill non-cancerous cells, p53 is a popular target for reducing toxicity. However, the reduction in DOX-induced cardiotoxicity (DIC) via p53 suppression is often at odds with the antitumor advantages of p53 reactivation. Therefore, in order to increase the effectiveness of DOX, there is an urgent need to explore p53-targeted anticancer strategies owing to the complex regulatory network and polymorphisms of the p53 gene. In this review, we summarize the role and potential mechanisms of p53 in DIC and resistance. Furthermore, we focus on the advances and challenges in applying dietary nutrients, natural products, and other pharmacological strategies to overcome DOX-induced chemoresistance and cardiotoxicity. Lastly, we present potential therapeutic strategies to address key issues in order to provide new ideas for increasing the clinical use of DOX and improving its anticancer benefits.

Phylogenetic analysis based on the ITS, matK and rbcL DNA barcodes and comparison of chemical contents of twelve Paeonia taxa in Türkiye

Twelve taxa of herbaceous Paeonia species were recorded in Türkiye. All definitions were performed morphologically and/or anatomically and there is no study based on DNA barcode sequences. Three barcode regions were sequenced to determine the phylogenetic relationships of Turkish Paeonia taxa. The chemical comparison of roots was also investigated. The taxons were collected between May and June 2021 from nine cities. Leaf materials were used for DNA isolation and ITS, matK and rbcL regions were amplified and sequenced. There was no difference among taxa in terms of rbcL sequences. But the ITS and matK regions distinguished 12 taxa and structured them in two groups. ITS region distinguished P. peregrina, P. arietina, and P. tenuifolia from other taxa, while matK region distinguished P. arietina and P. witmanniana from other taxa. Both barcode sequences actually showed that the registration of P. mascula subsp. arasicola was actually 100% similar to P. arietina. ITS was the most polymorphic region (n = 54) followed by matK (n = 9). These sequences could successfully discriminate Paoenia species from each other and diploid P. tenuifolia. The methanolic root (100 gr) extracts were examined for total phenolic and flavonoid content, and antioxidant activities. Significant variation was found for polyphenolic content, and antioxidant properties (TPC from 204.23 to 2343.89mg, TFC from 7.73 to 66.16mg, and FRAP from 523.81 to 4338.62mg). SC50 values of ABTS and DPPH were ranged from 115.08 to 1115.52μg/ml and 73.83 to 963.59μg/ml, respectively. It was concluded that 11 of 12 taxa had differences in terms of ITS and matK sequences and these region must be used for the correct identification of Turkish Paeonia.

Research Progress on the Relationship Between the Regulation of SLC6A4 Gene and Anxiety Disorders

Anxiety disorder is one of the most common mental disorders. Numerous studies have demonstrated the critical role played by genetic variables in the etiology of anxiety disorders. SLC6A4, which encodes serotonin transporter, is considered to be an important gene associated with anxiety susceptibility. The SLC6A4 gene's upstream promoter has a polymorphism region that has an impact on the transcriptional activity of the gene. Research has shown that this promoter polymorphism has a certain relationship with the occurrence of anxiety disorders and drug treatment. Anxiety disorders are also linked to SLC6A4 gene methylation and intron 2 (Stin2) polymorphism. Stin2 point and SLC6A4 gene methylation are all related to gene expression. This review summarizes the current research on the relationship between SLC6A4 gene promoter polymorphism, Stin2 polymorphism, and SLC6A4 gene methylation in the pathogenesis and drug treatment of anxiety disorder, to understand the current research progress of SLC6A4 gene expression in anxiety disorder.

Positive selection on ADAM10 builds species recognition in the synchronous spawning coral Acropora.

The reef-building coral Acropora is a broadcast spawning hermaphrodite including more than 110 species in the Indo-Pacific. In addition, many sympatric species show synchronous spawning. The released gametes need to mate with conspecifics in the mixture of the gametes of many species for their species boundaries. However, the mechanism underlying the species recognition of conspecifics at fertilization remains unknown. We hypothesized that rapid molecular evolution (positive selection) in genes encoding gamete-composing proteins generates polymorphic regions that recognize conspecifics in the mixture of gametes from many species. We identified gamete proteins of Acropora digitifera using mass spectrometry and screened the genes that support branch site models that set the "foreground" branches showing strict fertilization specificity. ADAM10, ADAM17, Integrin α9, and Tetraspanin4 supported branch-site model and had positively selected site(s) that produced polymorphic regions. Therefore, we prepared antibodies against the proteins of A. digitifera that contained positively selected site(s) to analyze their functions in fertilization. The ADAM10 antibody reacted only with egg proteins of A. digitifera, and immunohistochemistry showed ADAM10 localized around the egg surface. Moreover, the ADAM10 antibody inhibited only A. digitifera fertilization but not the relative synchronous spawning species A. papillare. This study indicates that ADAM10 has evolved to gain fertilization specificity during speciation and contributes to species boundaries in this multi-species, synchronous-spawning, and species-rich genus.

Towards Computational Modeling of Ligand Binding to the ILPR G-Quadruplex.

Using a combination of unconstrained and constrained molecular dynamics simulations, we have evaluated the binding affinities between two porphyrin derivatives (TMPyP4 and TEGPy) and the G-quadruplex (G4) of a DNA fragment modeling the insulin-linked polymorphic region (ILPR). Refining a well-established potential of mean force (PMF) approach to selections of constraints based on root-mean-square fluctuations results in an excellent agreement between the calculated and observed absolute free binding energy of TMPyP4. The binding affinity of IPLR-G4 toward TEGPy is predicted to be higher than that toward TMPyP4 by 2.5 kcal/mol, which can be traced back to stabilization provided by the polyether side chains of TMPyP4 that can nestle into the grooves of the quadruplex and form hydrogen bonds through the ether oxygen atoms. Because our refined methodology can be applied to large ligands with high flexibility, the present research opens an avenue for further ligand design in this important area.

Humoral Immune Responses to P. falciparum Circumsporozoite Protein (Pfcsp) Induced by the RTS, S Vaccine - Current Update.

Malaria vaccines targeting the circumsporozoite protein (CSP) of the P. falciparum parasite have been overall relatively promising. RTS, S is a pre-erythrocytic recombinant protein-based malaria vaccine that targets CSP. RTS, S effectiveness shows some limited success regardless of its 58% efficacy for severe disease. P. falciparum circumsporozoite protein (Pfcsp) has stood to be the main candidate protein for most pre-erythrocytic stage vaccines. Studies on the structural and biophysical characteristics of antibodies specific to CSP (anti-CSP) are underway to achieve fine specificity with the CSP polymorphic regions. More recent studies have proposed the use of different kinds of monoclonal antibodies, the use of appropriate adjuvants, ideal vaccination dose and frequency, and improved targeting of particular epitopes for the robust production of functional antibodies and high complement-fixing activity as other potential methods for achieving long-lasting RTS, S. This review highlights recent findings regarding humoral immune responses to CSP elicited by RTS, S vaccine.

The diversity of Plasmodium falciparum isolates from asymptomatic and symptomatic school-age children in Kinshasa Province, Democratic Republic of Congo

BackgroundUnderstanding Plasmodium falciparum population diversity and transmission dynamics provides information on the intensity of malaria transmission, which is needed for assessing malaria control interventions. This study aimed to determine P. falciparum allelic diversity and multiplicity of infection (MOI) among asymptomatic and symptomatic school-age children in Kinshasa Province, Democratic Republic of Congo (DRC).MethodsA total of 438 DNA samples (248 asymptomatic and 190 symptomatic) were characterized by nested PCR and genotyping the polymorphic regions of pfmsp1 block 2 and pfmsp2 block 3.ResultsNine allele types were observed in pfmsp1 block2. The K1-type allele was predominant with 78% (229/293) prevalence, followed by the MAD20-type allele (52%, 152/293) and RO33-type allele (44%, 129/293). Twelve alleles were detected in pfmsp2, and the 3D7-type allele was the most frequent with 84% (256/304) prevalence, followed by the FC27-type allele (66%, 201/304). Polyclonal infections were detected in 63% (95% CI 56, 69) of the samples, and the MOI (SD) was 1.99 (0.97) in P. falciparum single-species infections. MOIs significantly increased in P. falciparum isolates from symptomatic parasite carriers compared with asymptomatic carriers (2.24 versus 1.69, adjusted b: 0.36, (95% CI 0.01, 0.72), p = 0.046) and parasitaemia > 10,000 parasites/µL compared to parasitaemia < 5000 parasites/µL (2.68 versus 1.63, adjusted b: 0.89, (95% CI 0.46, 1.25), p < 0.001).ConclusionThis survey showed low allelic diversity and MOI of P. falciparum, which reflects a moderate intensity of malaria transmission in the study areas. MOIs were more likely to be common in symptomatic infections and increased with the parasitaemia level. Further studies in different transmission zones are needed to understand the epidemiology and parasite complexity in the DRC.

Complete sequences of six major histocompatibility complex haplotypes, including all the major MHC class II structures.

Accurate and comprehensive immunogenetic reference panels are key to the successful implementation of population-scale immunogenomics. The 5Mbp Major Histocompatibility Complex (MHC) is the most polymorphic region of the human genome and associated with multiple immune-mediated diseases, transplant matching and therapy responses. Analysis of MHC genetic variation is severely complicated by complex patterns of sequence variation, linkage disequilibrium and a lack of fully resolved MHC reference haplotypes, increasing the risk of spurious findings on analyzing this medically important region. Integrating Illumina, ultra-long Nanopore, and PacBio HiFi sequencing as well as bespoke bioinformatics, we completed five of the alternative MHC reference haplotypes of the current (GRCh38/hg38) build of the human reference genome and added one other. The six assembled MHC haplotypes encompass the DR1 and DR4 haplotype structures in addition to the previously completed DR2 and DR3, as well as six distinct classes of the structurally variable C4 region. Analysis of the assembled haplotypes showed that MHC class II sequence structures, including repeat element positions, are generally conserved within the DR haplotype supergroups, and that sequence diversity peaks in three regions around HLA-A, HLA-B+C, and the HLA class II genes. Demonstrating the potential for improved short-read analysis, the number of proper read pairs recruited to the MHC was found to be increased by 0.06%-0.49% in a 1000 Genomes Project read remapping experiment with seven diverse samples. Furthermore, the assembled haplotypes can serve as references for the community and provide the basis of a structurally accurate genotyping graph of the complete MHC region.

Genetic diversity and population structure analysis of Capoeta trutta (Heckel, 1843) in Turkey and Iraq based on mitochondrial d loop gene

Capoeta trutta, a species of cyprinid with economic importance thriving in fresh water, is considered to hold a substantial potential for commercial growth in Turkey and Iraq. In recent years, it has been observed that there has been a decrease in the populations of this species, which lives naturally in the Euphrates and Tigris river systems. For long-term fishing and conservation strategies, it is necessary to determine the genetic structure of the populations of this species and to take measures accordingly. In this study, a total of 125 fish samples from 8 populations were collected and the mtDNA D-loop site was analyzed by sequencing, and by determining the genetic structures of C. trutta populations, basic data were obtained for the sustainability and conservation of the stocks of the species. In the analyzes made for the target gene region, a total of 16 polymorphic regions and 22 haplotypes were determined; mean haplotype and nucleotide diversity were calculated as 0.847 and 0.00675, respectively. Pairwise FST values between populations, which were calculated based on haplotype frequencies, varied between −0.03136 and 0.45114 and were determined to be significant between certain populations. The results obtained in this study will contribute to the planning of effective strategies for the conservation and rehabilitation of future populations for both C. trutta and similar species.

Vitamin D Receptor Polymorphisms Among the Turkish Population are Associated with Multiple Sclerosis.

Multiple sclerosis (MS) is an inflammatory disease characterized by demyelination and axonal degeneration affecting the central nervous system. Among the genetic factors suggested to be associated with this disease are polymorphisms to the vitamin D receptor (VDR) gene. We tested the hypothesis that polymorphisms in the vitamin D receptor (VDR) gene are associated with MS. The aim of the study was to investigate the relationship of MS with the VDR gene Fok-I, Bsm-I and Taq-I polymorphisms among the Turkish population. This study contains 271 MS patients and 203 healthy controls. Genomic DNA was isolated from the samples and the VDR gene Fok-I, Bsm-I and Taq-I polymorphism regions were amplified by polymerase chain reaction (PCR). The PCR products were digested, and the genotypes were determined based on size of digested PCR products. Our results demonstrate associations between MS and the distribution of the VDR gene Fok-I T/T polymorphism genotype in a dominant model, VDR gene Fok-I T allele frequency, distribution of VDR gene Taq-I C/C polymorphism genotype in a dominant model and VDR gene Taq-I C allele frequency (Pearson test, p<0.05). However, there was no association between MS and the VDR gene Bsm-I polymorphisms for the genotype distribution (Pearson test, p>0.05) or allele frequency (Pearson test, p>0.05). Fok-I and Taq-I VDR gene polymorphisms are significantly associated with MS in dominant, homozygote and heterozygote inheritance models among the Turkish population.

Meta-Analysis of the Association Between 5-Hydroxytryptamine Transporter Gene-Linked Polymorphic Region and Functional Dyspepsia and its Subtypes.

Background: Association studies of variations in the 5-hydroxytryptamine (5-HT, serotonin) transporter gene-linked polymorphic region (5-HTTLPR) and functional dyspepsia (FD) have yielded contradictory results. Hence, we performed a meta-analysis to clarify inconsistencies between the 5-HTTLPR polymorphism with FD and it subtypes. Methods: We performed a literature search in PubMed, Embase, Web of Science, Cochrane Library, and CNKI, including articles published until March 2022. We calculated and pooled odds ratios (ORs) with their 95% confidence intervals (CIs) in Stata 15.0. Data extraction was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane Handbook for Systematic Reviews of Interventions. Results: The meta-analysis included six studies, comprising 488 cases and 1513 healthy controls. We did not observe a significant association between the 5-HTTLPR polymorphism and FD in the overall population. In subgroup analyses, the 5-HTTLPR polymorphism was significantly associated with FD-subtype epigastric pain syndrome (EPS) (SS vs. LL+LS, OR = 0.620, 95% CI: 0.414-0.930; SS vs. LS, OR = 0.640, 95% CI: 0.417-0.980; S vs. L, OR = 0.655, 95% CI: 0.471-0.911). However, no association was observed with the other subtype, postprandial distress syndrome (PDS). Conclusion: While the 5-HTTLPR polymorphism had no relationship with FD overall, splitting the disease into its subtypes revealed a clear association with EPS.

SPECIFIC CHARACTERISTICS OF MENTAL STATUS IN PATIENTS WITH RHEUMATIC ARTHRITIS DEPENDING ON SEX

The work is devoted to the study the specific characteristics of mental status in patients with different variants of polymorphic regions of the A1438-G gene of the serotonin receptor 2A (HTR2A), ill with rheumatoid arthritis, depending on gender, and to study the relationship between anxiety-depressive disorders and pain intensity and clinical signs of the disease. Materials and мethods used in the study. The distribution of genotype rate of serotonin receptor 5-HT2A A1438-G gene was studied in 100 patients with RA. Anxiety level was assessed by Spielberger State-Trait Anxiety Scale. Depressive status and depression severity was evaluated by Hamilton Depression Rating Scale. Females with GG genotype were found to have higher level of pain feelings and the presence of anxiety signs associated with depression symptoms, while in males with GG genotype had the prevalence of inflammatory component and the depression symptoms.In females with AA genotype pain syndrome indices were associated with high anxiety indices, and in females with AG genotype they were dependent on the presence or absence of anxiety and depression, while in males with AG genotype pain syndrome was associated with SA indices.