Variant Genotypes Research Articles

Genome Wide Association Study on Muscle Stiffness Identified Novel Locus for Predisposition to Muscle Strain Injury.

We aimed to screen the entire genome for genetic variants associated with passive muscle stiffness, which has been suggested as a risk factor for muscle strain injury. This genome-wide association study (GWAS) on passive muscle stiffness included 350 physically active young Japanese individuals. Three hamstring constituents were measured using ultrasound shear wave elastography. Skeletal muscle transcriptomes were compared across the genotypes of GWAS-identified variants in 48 healthy Japanese individuals. Association between GWAS-identified variants and history of muscle strain injury were examined in 1,428 Japanese athletes. Two loci on chromosome 11 demonstrated a genome-wide significant association with passive muscle stiffness of the biceps femoris long head (rs12807854 T/C: P = 5.19 × 10-10, rs78405694 T/C: P = 2.09 × 10-8; linear regression analysis adjusted for sex, age, and stretching exercise habits). Skeletal muscle RNA sequencing revealed significantly elevated expression of extracellular matrix-related genes in muscles carrying stiffness-increasing alleles of these variants. Among athletes, rs12807854 T/C was significantly associated with a history of muscle strain injury (P = 0.0254; logistic regression analysis adjusted for age, sex, competitive level, and main sport). Carriers of the C allele, associated with increased muscle stiffness, exhibited a heightened risk of muscle strain injury (odds ratio: 1.62; 95% confidence interval: 1.06-2.47 per C allele increase). In contrast, rs78405694 did not show a significant association with muscle strain injury in this population. A novel locus associated with passive muscle stiffness and muscle strain injury was identified. Elucidating the detailed mechanisms linking the identified locus to passive muscle stiffness may lead to the development of new strategies to prevent muscle strain injuries.

Relationship of Neurotropin-3 Gene Polymorphism with Cognitive Impairment in Bipolar Disorder.

Neurotropin-3 (NT-3), a marker of neural plasticity, is reported to be altered in bipolar disorder (BD). This study was designed to evaluate NT-3 gene polymorphism (rs 6489630, rs 6332, and rs 11063714) in BD and its association with disease severity and cognition. The study included 176 BD cases and 176 controls. All the participants were tested for NT-3 polymorphism and plasma NT-3. ACE-III scores were used to analyze cognition. The NT-3 polymorphism (rs 6489630) was associated with cognitive impairment in BD (P = .010). The attention score was found to be decreased in the CT genotype (P = .028) when compared to the CC and TT genotypes of the rs6489630 variant. The visuospatial ability score was decreased in the GG genotype (P = .044) compared to the AG genotype of the rs11063714 variant. BD patients with the maniac episode showed a decrease in levels of Neurotrophin-3 in comparison to both the control group (P = .045) and the remission group (P = .017). Plasma NT-3 was associated with the YMRS (r = -0.221, P = .003), HDRS (r = 0.209, P = .005) and visuospatial ability score (r = 0.180, P = .017) in patients with BD. Single nucleotide polymorphisms of NT-3 are associated with cognitive dysfunction in BD.

High plasma concentration of tenofovir alafenamide in people living with HIV with ABCB1 genetic variants

We aimed to analyze the relationships between single nucleotide polymorphisms in the ATP-binding cassette transporter B1 (ABCB1) and G2 (ABCG2) genes and plasma concentrations of tenofovir alafenamide (TAF), tenofovir (TFV), and emtricitabine (FTC). We recruited 10 people living with HIV receiving once-daily treatment with a single tablet containing TAF (25mg), FTC (200mg), and bictegravir (50mg). Peripheral blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 12, and 24h after administration. Plasma concentrations of TAF, TFV, and FTC were quantified using liquid chromatography-tandem mass spectrometry. Genotyping for allelic variants of ABCB1, including 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642), 4036 A>G (rs3842) and ABCG2 421C>A (rs2231142), was performed using TaqMan Drug Metabolism Assays. None of the genotypes for ABCB1 1236C>T, 2677G>T/A, 3435C>T, and ABCG2 421C>A exhibited correlations with plasma concentrations of TAF, TFV, and FTC. In contrast, individuals with the ABCB1 4036 AG genotype (188.7ng/mL, n=3) exhibited a significantly higher mean peak plasma concentration of TAF than those with the ABCB1 4036 AA genotype (67.7ng/mL, n=7) (p=0.0167). However, these genotypes did not affect the elimination of terminal half-lives of TAF. The allelic variant ABCB1 4036 A>G is associated with reduced protein expression and function of ABCB1. Individuals with this genetic variant exhibited significantly high peak plasma concentrations of TAF, potentially due to the reduced expression of efflux transporters in the intestines linked to this variant.

Comparison of autism domains across thirty rare variant genotypes.

A number of Neurodevelopmental risk Copy Number Variants (ND-CNVs) and Single Gene Variants (SGVs) are strongly linked to elevated likelihood of autism. However, few studies have examined the impact on autism phenotypes across a wide range of rare variant genotypes. This study compared Social Communication Questionnaire (SCQ) scores (total and subdomains: social, communication, repetitive behaviour) in 1314 young people with one of thirty rare variant genotypes (15 ND-CNVs; n=1005, 9.2±3.5 years and 15 SGVs; n=309, 8.3±4.0 years). Comparisons were also conducted with young people without known genetic conditions (controls; n=460, 10.6±3.4 years) and with idiopathic autism (n=480, 8.6±3.2 years). The prevalence of indicative autism (SCQ ≥ 22) was higher in those with a rare variant genotype compared to controls (32% vs 2%; OR=43.1, CI=6.6-282.2, p<0.001) and in those with SGVs compared to ND-CNVs (53% vs 25%; OR=4.00, CI=2.2-7.3, p=0.002). The prevalence of indicative autism varied considerably across the 30 rare variant genotypes (range 10-85%). SGVs were associated with greater impairment in total, social, communication and repetitive behaviour subdomains than ND-CNVs. However, genotype explained limited variation in these scores (η2 between 11.8 and 21.4%), indicating more convergence than divergence in autism phenotype across rare variant genotypes. Comparisons with young people with idiopathic autism indicated no differences compared to those with ND-CNVs, whereas those with SGVs showed greater communication and less repetitive behaviour. The likelihood of autism was higher across all rare variant genotypes, with individuals with SGVs showing higher prevalence and greater impairment compared to those with ND-CNVs. Despite subdomain-specific patterns, there was no strong evidence for specific genotype-phenotype associations. This suggests that rare variant genotypes alone may have limited predictive value for autism phenotypes and that other factors like polygenic risk and the environment are likely to play a role. Further research is needed in order to understand these influences, improve risk prediction and inform genetic counselling and interventions. This work was funded by the Tackling Multimorbidity at Scale Strategic Priorities Fund programme (MR/W014416/1) (van den Bree) delivered by the Medical Research Council and the National Institute for Health Research in partnership with the Economic and Social Research Council and in collaboration with the Engineering and Physical Sciences Research Council. NIMH U01 MH119738-01 (van den Bree), IMAGINE study (Medical Research Council UK: MR/T033045/1; MR/N022572/1; and MR/L011166/1) (van den Bree) and Medical Research Council UK Centre Grant (MR/L010305/1) (Owen). SJRAC is funded by a Medical Research Foundation Fellowship (MRF-058-0015-F-CHAW). We would also like to acknowledge NIH 1R01MH110701-01A1 (PI Mulle), U01MH119736 (CEB), R21MH116473 (CEB), and R01MH085953 (CEB), and the Simons Foundation (SFARI Explorer Award to CEB).

The Role of Candidate Polymorphisms in Drug Transporter Genes on High-Dose Methotrexate in the Consolidation Phase of the AIEOP-BFM ALL 2009 Protocol.

High-dose methotrexate (HD-MTX) infusions are commonly used to consolidate remission in children with acute lymphoblastic leukemia (ALL). We investigate the potential role of candidate polymorphisms in SLCO1B1 (rs4149056 and rs2306283), ABCB1 (rs1045642), ABCC2 (rs717620), ABCC3 (rs9895420), and ABCC4 (rs7317112) drug transporters genes on HD-MTX pharmacokinetics and patients' outcome (meant both as relapse and drug-related toxicities) in an Italian cohort of 204 ALL pediatric patients treated according to the AIEOP-BFM ALL 2009 protocol. TaqMan SNP genotyping assays determined patient's genotypes. Measurements of HD-MTX plasma concentration were available for 814 HD-MTX courses in 204 patients; MTX clearance was estimated by a two-compartmental linear pharmacokinetic model with first-order elimination and a Bayesian approach, via ADAPT. Independent contributions of age and ABCC4 SNP rs7317112 (A>G, intronic) on MTX clearance were detected in a multivariate analysis (p = 1.57 × 10-8 and p = 2.06 × 10-5, respectively), suggesting a delayed elimination of the drug in older patients and an accelerated one in carriers of the variant GG genotype. After multiple corrections, the association between ABCC2 SNP rs717620 (-24 C>T) and severe hematological toxicity was found (p < 0.005). Moreover, SLCO1B1 SNP rs4149056 (c.521T>C, p.V174A) affected patients' outcomes: carriers of the variant C allele presented a reduced risk of relapse compared to wild-type TT (hazard risk: 0.27, 95% confidence interval [CI]: 0.08-0.90, p = 0.037). Taken together, these data highlighted the importance of variants in drug transporters genes on HD-MTX disposition in the AIEOP-BFM ALL 2009 protocol consolidation phase, and their putative role as predictive markers of outcome.

Characteristics of polymorphism of genes involved in the regulation of glucose metabolism and steroid hormone synthesis in patients with polycystic ovary syndrome

Background: Polycystic ovary syndrome is an urgent problem of gynecological endocrinology. Currently, a number of genes have been studied that control glucose metabolism and are involved in the synthesis, conversion into an active form and transport of steroid hormones, mutations in which with a certain degree of reliability can serve as a diagnostic criterion for polycystic ovary syndrome. Aim: The aim of this study was to evaluate the PPARG Pro12Ala, INS 223HphI AT, and SHBG (TAAAA)n gene polymorphisms in patients with polycystic ovary syndrome and in healthy individuals. Materials and methods: The polymerase chain reaction method and restriction fragment length polymorphism analysis were used. The frequencies of alleles and genotypes of polymorphic variants were studied in 136 women with polycystic ovary syndrome and 47 women in the control group: Pro12Ala (PPARG gene), 223HphI AT, (INS gene) and (TAAAA)n repeats (SHBG gene). Results: The distribution of the allele and genotype frequencies for the PPARG (rs1801282) and INS (rs689) genes in patients with polycystic ovary syndrome and in healthy individuals did not differ. The distribution of the genotype frequencies in the group of women with polycystic ovary syndrome differed (p = 0.02) from that in the control group for the (TAAAA)n polymorphism in the SHBG gene. In the presence of a long repeat in the SHBG gene in at least one of the homologous chromosomes, the probability of a woman having polycystic ovary syndrome increases by 2.5 times. Patients with a verified A/A genotype (INS), in the presence of an SHBG gene allele with a long repeat, have a ten-fold higher risk of developing polycystic ovary syndrome than women with SHBG gene short alleles. Conclusions: Patients with long repeats in the SHBG gene are at risk for developing polycystic ovary syndrome with phenotypes A, B, and C, especially in combination with the presence of the A/A genotype, class I (INS).

Effector genes of type III secretion system and biofilm formation in virulent Pseudomonas aeruginosa isolates carrying bla KPC-2 and bla PDC-5 genes in hospital environment.

Introduction. In critically ill patients, the occurrence of multidrug-resistant Pseudomonas aeruginosa infection is a significant concern, given its ability to acquire multidrug-resistant, form biofilms and secrete toxic effectors.Hypothesis or Gap Statement. In Brazil, limited data are available regarding the prevalence of dissemination, and the impact of the type III secretion system (T3SS) on toxin production and biofilm formation in clinical isolates of P. aeruginosa.Aim. This study investigates the dissemination of virulent P. aeruginosa harbouring the bla KPC-2 and bla PDC-5 genes, the presence of T3SS genes and their biofilm-forming capability.Methodology. A total of 128 non-duplicate clinical isolates of carbapenem-resistant P. aeruginosa (CRPA) from different sources collected from eight hospitals were examined. Detection was performed by PCR of the T3SS genes (exoU, exoT, exoS and exoY), carbapenemases (bla KPC, bla GIM and bla NDM) and beta-lactamase gene (bla PDC). PFGE and phenotypic biofilm production (initial adhesion assay and biofilm cell concentration) were performed.Results. We found exoT+ (86%) to be the most frequent genotypic variant, followed by exoY+ (61%). Notably, a substantial proportion of isolates exhibited the simultaneous presence of exoU+ and exoS+ genes, along with a high prevalence of bla KPC-2 + (64%) and bla PDC-5 + (64%) among the disseminated clones in the evaluated region. Additionally, 78% of the isolates demonstrated biofilm-forming capability, and two distinct clonal profiles were identified and disseminated both intra- and inter-hospital. Also, it was revealed that the exoU genotype was significantly more frequent among multidrug-resistant strains.Conclusion. These findings underscore the ability of multiple virulent and biofilm-producing clones of CRPA to propagate effectively.

Milk productivity of simmental cattle by combined kappacasein and somatotropin genes

The economically important productive traits of cattle that contribute to the development of the dairy industry are considered to be abundant milk yield, protein and fat content in milk. In recent years, breeders have focused their attention on cattle breeding programmes based on molecular genetic research methods. The potential of animal productivity largely depends on genetic variants of marker genes present in the genotype of an individual. The genes of kappa-casein and somatotropin are considered to be promising DNA markers, as they are responsible for qualitative and quantitative traits of cattle productivity. In this work we studied milk productivity of 84 cows of Simmental breed from the breeding plant in the Urals by kappa-casein and somatotropin genes, as well as by complex genes. On the gene kappa-casein on milk yield in advantage are individuals with genotypes CSN3AB 6937,6 kg. The higher content of protein in milk, milk fat and protein yield, as well as the sum of nutrients were recorded in cows with CSN3BB genotypes 3.40%, 282.5 kg, 234.2 kg and 516.7 kg, respectively. In terms of somatotropin gene, cows with GHVV genotypes had the most abundant milk production 7160.0 kg. In terms of protein-milk yield, coevals with GHLL genotypes are more productive 3.4 %. The sum of nutrients, milk fat and protein yield is more established in milk of cows with GHVV genotypes 522.7 kg, 293.6 kg and 229.1 kg, respectively. All nine possible variants of complex genotypes for kappa-casein and somatotropin genes occur in this Simmental herd: AA/LV 26 cows; AA/LL 14; AA/VV 12; AB/LL 13; AB/LV 10; AB/VV 2; BB/LL 4; BB/ VV 2; BB/LV 1. Data processing on the effect of complex genotypes on milk productivity included a number of 10 cows or more. Higher milk yield, milk protein content, milk fat and protein yield, and nutrient sum were found in AB/LL complex genotypes: 6756.0 kg, 3.4 %, 277.0 kg and 229.7 kg, 506.7 kg, respectively. Significant differences were found between cow groups in the content of mass fraction of protein.

Pharmacogenetic associations of GATA4 and KCNQ1 with ibrutinib cardiovascular toxicity.

Ibrutinib treatment is often complicated by cardiovascular side effects (CVSEs). The objective of this retrospective pharmacogenetic study is to replicate a previously reported association of 'high-risk' patients, who are homozygous carriers of at least two of GATA4 rs804280 AA, KCNQ1 rs163182 GG, and KCNQ1 rs2237895 AA, with increased risk of hypertension or atrial fibrillation, and explore associations for other pharmacogenes (e.g. CYP3A4, CYP3A5, CYP2D6, and ABCB1) with ibrutinib CVSEs. Univariate associations with P < 0.05 were adjusted for significant pretreatment cardiovascular conditions. In total 57 patients were included in the analysis. In the primary analysis, 'high-risk' patients were not more likely to experience hypertension or atrial fibrillation (70 vs. 41%, chi-square P value = 0.06). In secondary analyses, 'high-risk' patients were more likely to experience any CVSE during treatment (75 vs. 41%, P = 0.013), develop a cardiac rhythm or function disorder (65 vs. 24%, P = 0.008), and have a treatment modification due to CVSE (45 vs. 8%, P = 0.004). Additionally, high-risk homozygous variant genotypes of KCNQ1 rs163182 GG and rs2237895 AA were each associated with an increased likelihood of treatment modifications due to CVSE (40 vs. 11%, P = 0.021 and 45 vs. 9%, P = 0.004, respectively) and cardiac rhythm or function disorders (60 vs. 27%, P = 0.037 and 60 vs. 27%, P = 0.037). This study found supportive evidence that 'high-risk' genotype was associated with increased ibrutinib CVSEs. Validation of these associations is necessary before prospective trials testing whether personalized ibrutinib treatment approaches improve clinical outcomes.

Ongoing measles outbreak in Romania: Clinical investigation and molecular epidemiology performed on whole genome sequences.

Romania is currently facing a prolonged measles outbreak. The aim of the study was to analyse the circulating human measles virus (HMV) strains by combining whole genome sequencing (WGS) with phylogenetic analysis, with a focus on the haemagglutinin gene. We conducted an observational study in the first five months of 2024, in which 168 patients diagnosed with measles were randomly included. We have evaluated the clinical and epidemiological differences between children and adults. Screening for samples to be sequenced was performed with a commercial kit (PrimerDesign). WGS was done on Illumina MiSeq platform and phylogenetic analysis was performed with ML FastTree. No significant epidemiological and clinical differences between patients in the two age groups were identified. WGS was successfully performed for a number of 124 HMV strains. Genotype analysis indicated all the sequences as D8, except one that was B3. Phylogenetic analysis identified two well supported clusters, suggestive for at least two local transmission networks in Romania. One large transmission network (n = 108) consisted of sequences both from adults and children. Only one sequence from outside Romania (reported in Russia in 2023) clustered within this group. Another small transmission cluster was identified (14 sequences of which 11 from patients infected in the spring of 2024 and three in 2022). A few differences between the two co-circulating viral variants/clusters were observed. The median duration of hospitalisation was 2 days longer for patients in smaller cluster compared to those in the larger one (p = 0.019). Furthermore, these two clusters presented different mutation profiles in the hemagglutinin (HA) and neuraminidase (N) genes with implications for molecular surveillance. The current measles epidemic in Romania is driven mainly by two D8 genotype variants with different mutation profiles and slightly different severity of the disease, highlighting the usefulness of sustained molecular surveillance.

AMPD1 and MTHFR genes are not associated with calcium levels in rheumatoid arthritis patients with methotrexate therapy in Indonesia

Rheumatoid Arthritis (RA) is a chronic and progressive autoimmune disease that affects synovial tissues has greater risk of developing secondary osteoporosis (OP). In particular, polymorphisms in Adenosine Monophosphate Deaminase 1 (AMPD1) and Methylenetetrahydrofolate Reductase (MTHFR) affect the outcome of methotrexate (MTX) treatment in patients with RA. Therefore, this study aimed to determine the association of AMPD1 rs17602729, MTHFR C677T, and MTHFR A1298C polymorphisms with MTX activity in RA patients. A retrospective design was adopted to collect data from medical records and blood samples of 99 patients experiencing outpatient care at a referral hospital in Bandung. The inclusion criteria were patients diagnosed with RA, aged 18–59 years, and receiving MTX therapy for ≥ 6 months. DNA was isolated and then amplified using Polymerase Chain Reaction (PCR), and genotyping was performed with Sanger sequencing. The kinetic photometric method was used to measure the levels of calcium in the samples. The results showed that there is no significant association between the MTHFR C677T genotype variant or allele with calcium levels, as indicated by p-values of 0.177 and 0.174, respectively. The association between the MTHFR A1298C genotype variant or alleles with calcium levels was also not significant (p = 0.206 and p = 0.090, respectively). However, most patients had normal calcium levels (76 patients; 77.6%) with the MTHFR C677T genotype variant CC and the MTHFR A1298C genotype variant AA (84 patients; 84.9%). AMPD1 rs17602729 in all patients had a CC genotype with normal calcium levels. The results suggested that there was no significant association between the genetic variation of AMPD1 rs17602729, MTHFR C677T, and MTHFR A1298C with serum calcium levels in patients with RA receiving MTX therapy.

GSTP1 and GSTO1 Variant Alleles Affect Susceptibility to Helicobacter pylori Infection and Severity of Helicobacter pylori-Associated Clinical Manifestations.

Considering the mutual relationship between redox disbalance and inflammation in Helicobacter pylori (HP) infection, we aimed to evaluate whether the polymorphisms in antioxidant glutathione transferases genes (GSTP1 rs1695, GSTP1rs1138272, GSTO1 rs4925 and GSTO2 rs156697) modify susceptibility to HP infection, as well as the severity of HP-associated gastric manifestation development. Therefore, GST gene polymorphisms were determined via the appropriate PCR in 101 HP-positive and 107 HP-negative patients. Our results show that carriers of the GSTP1*G/G variant genotype (rs1695) or at least one GSTP1*T variant allele (rs1138272) were more prone to the development of HP-positive gastritis compared with reference allele carriers (OR = 3.21, 95%CI = 1.15-8.91, p = 0.025 and OR = 2.31, 95%CI = 1.14-4.89, p = 0.021, respectively), which was confirmed by haplotype analysis. HP-positive carriers of the GSTO1*A variant allele showed increased risk of developing gastric atrophy and precancerous gastric lesions compared with the reference one (OR = 2.49, 95%CI:1.04-5.96, p = 0.04 and OR = 2.98, 95%CI = 1.21-7.34, p = 0.018, respectively). HP-positive carriers of the GSTO2*G variant allele were less prone to developing moderate/severe inflammatory infiltration (OR = 0.35, 95%CI = 1.04-5.96, p = 0.04), whereas the GSTP1*T variant allele was significantly associated with active inflammation (OR = 4.09, 95%CI = 1.04-5.96, p = 0.042). In conclusion, antioxidant GST genetic propensity seems to have an important impact on both acute and chronic forms of HP infection.

Evaluation of ACE I/D and ATIR A1166C variants in patients with diabetes mellitus with and without peripheral neuropathy in Turkish patients

Objective Type 2 Diabetes Mellitus (T2DM) can lead to long-term vascular complications such as diabetic peripheral neuropathy (DPN). This study aimed to investigate the role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) and angiotensin II type 1 receptor (AT1R) A1166C variants in the predisposition to T2DM in the Turkish population and their association with DPN. Methods The study included 90 T2DM patients (42 with DPN) and 50 healthy individuals. ACE I/D and ATIR A1166C gene regions were analyzed for the variant. Both the general genotype distribution of these variants and the observed genotype ratios were examined separately. Results In the T2DM group, the proportion of individuals with the AA genotype of the AT1R A1166C variant was lower than in the control group, and the proportion of individuals with the AC genotype was higher. There was no significant difference in the genotype distribution between the groups for the ACE I/D variant. There was no significant difference in the genotype distribution of the ACE I/D and ATIR A1166C variants in patients with and without DPN. Conclusion In the Turkish population, no significant difference was observed in the overall genotype distribution of ACE I/D and AT1R A1166C variants between T2DM patients and healthy individuals, whereas the AC genotype of the AT1R A1166C variant was more frequent in T2DM patients, and the AA genotype was less frequent. For both variants, no significant difference was observed in the genotype distribution between T2DM patients with and without DPN.

An IL-6 promoter variant (-174 G/C) augments IL-6 production and alters skeletal muscle transcription in response to exercise in mice.

Interleukin-6 (IL-6) is produced and secreted by skeletal muscle cells during exercise and plays an important role in mediating metabolic responses to exercise. The promoter region of the IL-6 gene contains a common genetic variant (-174 G/C, rs1800795), which may alter responses to exercise training. To isolate the impact of this gene variant on exercise-induced IL-6 expression and skeletal muscle transcription responses following exercise, we generated knock-in mice with a GG or variant CC genotype for the murine homolog of rs1800795. The overall gross metabolic phenotype of resting mice was similar between genotypes; however, following acute treadmill running, the variant CC genotype was associated with a greater increase in skeletal muscle Il6 mRNA and circulating IL-6. Furthermore, we observed that mice with the variant CC genotype exhibited sex-specific differences in skeletal muscle master metabolism regulatory genes and had greater increases in genes controlling mitochondrial biogenesis in skeletal muscle post exercise. However, there was no effect of genotype on exercise-induced skeletal muscle glycogen depletion, circulating free fatty acids, blood glucose and lactate production, or exercise-responsive gene expression in subcutaneous fat. These findings suggest that the IL-6 promoter variant -174 G/C may result in enhanced skeletal muscle adaptations in response to exercise training and could mean that individuals with the "C" allele may more readily gain improvements in metabolic health in response to exercise training.NEW & NOTEWORTHY Interleukin-6 (IL-6) is produced and secreted by skeletal muscle during exercise and mediates metabolic responses to exercise. A common variant in the IL-6 promoter region (-174G/C) may alter responses to exercise training. Mice with the variant "CC" genotype exhibited higher skeletal muscle IL-6 mRNA and circulating IL-6 levels post exercise, as well as altered skeletal muscle gene transcription. This suggests that this variant might enhance muscle adaptations to exercise, potentially benefiting metabolic health.

New Genetic Variations in RNA-binding Protein Gene and Breast Cancer Risk: A Case-Control Study.

LIN28, a highly conserved RNA-binding protein, regulate a wide variety of post-transcriptional cellular processes. The current study aimed to identify genetic variants of five single nucleotide polymorphisms (SNPs) in the LIN28B gene (rs221634, rs22163, rs314276, rs9404590, and rs12194974) and their association with Breast cancer. 220 patients and 230 controls were genotyped by the RFLP assay for Lin28B gene variants. Odds ratio analysis was used to determine the association between Lin28B variants and breast cancer. Haplotype analysis was performed to determine the combined impact of the investigated variants on BC. Novel in-silico analysis were performed to predict the potential functions of these polymorphisms, as well. Patients carrying all variant genotypes for lin28B rs221634 (codominant, dominant, recessive, and allelic inheritance models), rs221635 (codominant and dominant genotypes), and rs9404590 (codominant, dominant, and inheritance model). Significant associations between reduced cancer risk and rs12194974 and rs314276 were found in codominant, dominant, recessive, and allele inheritance models. According to haplotype analysis of rs9404590, rs12194974, rs314276, rs221634, and rs221635 SNPs ,the GGCTT, GGCAT, TGCAC, TGCTC, GGCAC, GGCTC, and GGAAC haplotypes are associated with an increased risk of BC, whereas the TACAT and TAAAT haplotypes were associated with a decreased risk of BC. The splicing enhancers (ESE) binding site was found to be altered by the SNPs rs9404590, rs12194974, and rs314276, according to in-silico analysis. Breast cancer susceptibility appears to be linked to genetic variations in the Lin28B gene, and haplotypes in this region have been linked to increased risk.

In Vivo Imaging of Cardiac Attachment of TcI and TcII Variants of Trypanosoma cruzi in a Zebrafish Model.

Trypanosoma cruzi, the etiological agent of Chagas disease, is a parasite known for its diverse genotypic variants, or Discrete Typing Units (DTUs), which have been associated with varying degrees of tissue involvement. However, aspects such as parasite attachment remain unclear. It has been suggested that the TcI genotype is associated with cardiac infection, the most common involved site in chronic human infection, while TcII is associated with digestive tract involvement. Traditional models for T. cruzi infection provide limited in vivo observation, making it challenging to observe the dynamics of parasite-host interactions. This study evaluates the cardiac attachment of trypomastigotes from TcI and TcII DTUs in zebrafish larvae. Labeled trypomastigotes were injected in the duct of Cuvier of zebrafish larvae and tracked by stereomicroscopy and light-sheet fluorescence microscopy (LSFM). Remarkably, it was possible to observe TcI parasites adhered to the atrium, atrioventricular valve, and circulatory system, while TcII trypomastigotes demonstrated adhesion to the atrium, atrioventricular valve, and yolk sac extension. When TcI and TcII were simultaneously injected, they both attached to the heart; however, more of the TcII trypomastigotes were observed attached to this organ. Although TcII DTU has previously been associated with digestive tissue infection, both parasite variants showed cardiac tissue attachment in this in vivo model.

STRAIN PRODUCTION IN INDUSTRIAL HEMP GENOTYPES – COMPARATIVE ANALYSIS

The study evaluated the stem production of ten fiber hemp genotypes. The research was conducted within the ARDS Lovrin. The field experiments were located on a chernozem soil, of medium fertility. The fiber hemp genotypes were designated with numerical codes, 721 to 730. Each genotype was cultivated in replicates. The comparative crop was under non-irrigated conditions. The plants samples were harvested within each variant, and according to the experimental protocol they were left to dry on the ground for a few days, placed "in scissors". After drying and shaking off the leaves, the stems were weighed. The stem yield (Y) varied between Y = 8800±260.58 kg ha-1 (genotype 724) and Y = 11236±260.58 kg ha-1 (genotype 728). The analysis of the results was done in relation to genotype 721 (control), as well as in relation to the mean value of the experiment (Y_m). Compared to the control variant (genotype 721, Y = 9840.00±260.58 kg ha-1), genotype 728 (***), genotype 730 (**) and genotype 722 (*) showed positive differences, according to LSD. Compared to the mean of the experiment (Y_m = 9861.40 kg ha-1) genotype 728 showed positive differences at the p&lt;0.001 level (***), and genotypes 722 and 730 at the p&lt;0.01 level (**). The yield increase for stem production, compared to the mean value of the experiment, was at the level of DY = 960.60 kg ha-1 (genotype 722), DY = 983.60 kg ha-1 (genotype 730), and DY = 1374.6 kg ha-1 (genotype 728), respectively. Cluster analysis facilitated the grouping of genotypes based on Euclidean distances (Coph.corr. = 0.910). The recorded results highlighted genotypes with advantages in stem production, important for the hemp fiber breeding program.

Significance Of Gene Polymorphisms In Joint Destruction In Reactive Arthritis

in patients with reactive arthritis (ReA), cytokines produced by Th17 cells, one of them IL17, affect cell differentiation, recruitment, activation of immune cells, and release of antimicrobial peptides. Among the cytokines of the IL-17 family, it is IL-17A that is of decisive importance in the induction of pathological bone resorption through direct activation of osteoclast precursors during the formation of the articular syndrome The aim of our work was to study the distribution of allele and genotype frequencies of the polymorphic region G197A (rs2275913) of the IL-17A gene in patients with ReA. As a result of the study, there were no significant differences in the distribution of alleles of the G197A polymorphism of the IL-17A gene in patients with ReA and apparently healthy people. But when comparing genotypic variants, we revealed differences: healthy GG and mutant AA genotypes were more common in patients, while the heterozygous GA genotype was more common in healthy people

Genetic Association Study of Acetylcholinesterase (ACHE) and Butyrylcholinesterase (BCHE) Variants in Sudden Infant Death Syndrome (SIDS).

Sudden infant death syndrome (SIDS) is the leading cause of death among infants aged between one month and one year. Altered enzyme activities or expression of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been observed in SIDS patients that might lead to disturbed autonomic function and, together with other risk factors, might trigger SIDS. To explore the contribution of AChE and BChE from a genomic viewpoint, we sought to investigate the association between SIDS and selected single nucleotide polymorphisms (SNPs) in the ACHE and BCHE genes. In this case-control study, 13 potentially regulatory SNPs were selected from ACHE and BCHE and were genotyped in 201 SIDS cases and 338 controls. The association of SIDS with the 11 successfully genotyped candidate variants was examined using statistical analyses of overall or stratified cases and haplotype analyses. No significant overall associations were observed between SIDS and ACHE and BCHE variants in allele, genotype, and haplotype analyses. In subgroup analyses, eight variants were found to be nominally associated with SIDS, though these associations did not remain statistically significant after correction for multiple comparisons. One haplotype (T-C-G-C-C in rs3495-rs1803274-rs1355538-rs2048493-rs1126680) of BCHE was associated with the female SIDS subgroup (57.3% in controls vs. 46.3% in female SIDS cases, p = 0.010). The selected variants in ACHE and BCHE were not overall associated with SIDS in this study, and thus cannot generally explain the previously reported dysregulation of enzyme activities in SIDS. However, some evidence of association in subgroups and a possible contribution of variants other than those tested here would need to be explored in larger studies.

Association of maternal folic acid supplementation and offspring MTRR gene polymorphism with congenital heart disease: a hospital-based case-control study in Han population

BackgroundAlthough many studies shown that the risk of congenital heart disease (CHD) was closely related to genetic and environmental factors, the exact mechanism was still unclear. This study was to assess the association of maternal folic acid supplementation (FAS), the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene polymorphisms in offspring and their interaction effects with the risk of CHD and its subtypes.MethodsA case-control study was conducted on 595 children with CHD and 605 healthy child controls. The multivariate logistic regression model was used to assess the association of maternal FAS, offspring MTRR gene polymorphisms and their interaction effects with CHD and its subtypes.ResultsThis study shown that maternal FAS was significantly associated with a reduced risk of CHD (OR = 0.55, 95%CI: 0.36–0.83) and its subtypes including ASD (OR = 0.25, 95%CI: 0.14–0.45), VSD (OR = 0.42, 95%CI: 0.27–0.64), and CTD (OR = 0.23, 95%CI: 0.09–0.59) in offspring. Offspring MTRR gene polymorphisms at rs162048 (GG vs. AA: OR = 2.05, 95%CI: 1.35–3.13), rs1802059 (AA vs. GG: OR = 5.13, 95%CI: 2.15–12.23; GA vs. GG: OR = 1.81, 95%CI: 1.35–2.43), rs10380 (TT vs. CC: OR = 2.27, 95%CI: 1.20–4.31) and rs1801394 (GG vs. AA: OR = 1.58, 95%CI: 1.02–2.42) were significantly associated with the risk of CHD, and similar results were also found for three subtypes of CHD. Additionally, a statistically significant interaction effect between maternal FAS and offspring MTRR gene polymorphism at rs1802059 was observed (OR = 0.38, 95%CI: 0.15–0.94). Among children who had a variant genotype at rs1802059, the risk of CHD was significantly decreased when their mother used folate for this pregnancy compared with mothers not using folate.ConclusionsIn those of Chinese descent, maternal FAS and offspring MTRR gene polymorphisms are significantly associated with the risk of CHD and its three subtypes. Furthermore, maternal FAS may help to offset some of risks of CHD due to offspring MTRR genetic variants. However, more studies with prospective designs and larger samples are needed to confirm our findings.Trial registrationRegistration number: ChiCTR1800016635; Registration time: 14/06/2018.