Search Results (105)

Background/Objectives: Lactate (LA) is a key metabolite in exercise metabolism, transported across cell membranes by monocarboxylate transporters (MCTs). Although genetic variation in MCT genes has been linked to LA kinetics, evidence in athletic populations remains limited. This study investigated nine MCT1 polymorphisms (rs4301628, rs12028967, rs10857983, rs3789592, rs10776763, rs1049434, rs6537765, rs7556664, rs7169) in relation to LA metabolism. Methods: 337 Polish and Czech males (elite athletes, sub-elite competitors, physically active controls) performed two maximal Wingate tests. Buccal swabs were collected for DNA extraction and single nucleotide polymorphism (SNP) genotyping. LA was assessed before and after the tests. Results: Five variants (rs3789592, rs7556664, rs7169, rs1049434, rs6537765) remained significantly associated with LA measured 30 min after the second Wingate (LA30′) and delta clearance capacity (DCC) in elites (codominant and recessive models: p = 0.01–0.03; false discovery rate (FDR)-adjusted p = 0.02–0.04). Rs10776763 showed the broadest associations, surviving FDR for LA30′ in all models (p = 0.003–0.03; FDR-adjusted p = 0.01–0.03) and for LA accumulation capacity (ACC) in the recessive model (p = 0.01; FDR-adjusted p = 0.03). Rs12028967 also supported a clearance role, with LA30′ significant in elites (p = 0.004; FDR-adjusted p = 0.01) and DCC in the overall cohort (p = 0.02; FDR-adjusted p = 0.03). In contrast, rs4301628 and rs10857983 demonstrated isolated LA30′ effects in elites (p = 0.004–0.01; FDR-adjusted p = 0.01), and no production-phase endpoint other than rs10776763 survived FDR; ACC remained significant in the recessive model (p = 0.01; FDR-adjusted p = 0.03). Conclusions: The results suggest that MCT1 polymorphisms contribute to differences in LA metabolism and warrant replication in larger, more diverse cohorts. Full article

Background/Objectives: Orofacial clefts (OFCs) are among the most common birth defects globally, sometimes exacerbated by adverse drug reactions (ADRs) from corticosteroids and antiepileptics. Comprehending the pharmacogenomic and pharmacogenetic elements that lead to ADRs is essential for enhancing precision medicine and clinical outcomes. This study examines rare genetic variants in drug-metabolizing and drug-transporting genes among Ghanaian and Nigerian families with a history of OFCs, intending to assess their pathogenicity and functional implications. Methods: We recruited 104 Ghanaian families and 26 Nigerian families, generating whole-genome sequencing (WGS) data from 390 individuals (130 case-parent trios). DNA isolated from saliva and buccal swab samples underwent WGS, and subsequent WGS data were analyzed through extensive bioinformatics analyses. Variants were called and annotated using the GATK workflow. The HOPE in silico modeling tool evaluated the structural impact of genetic variants on encoded proteins, while molecular docking using PyRx examined alterations in ligand binding affinity. Results: Our study revealed pathogenic variants in vital genes associated with drug metabolism and transport, specifically CYP1A2, CYP2C18, CYP27A1, CYP2B6, SLC6A2, and ABCC3. Structural modeling research demonstrated substantial size, charge, conformation, and hydrophobicity variations between wildtype and mutant proteins. Variants positioned near conserved regions or within functional domains were anticipated to be deleterious, potentially compromising protein function and ligand interactions. Molecular docking studies verified changes in binding affinities between wildtype and mutant proteins for common ligands. The identified variations were linked to the metabolism of frequently used pharmaceuticals in Africa, such as caffeine, ketoconazole, efavirenz, carbamazepine, and artemether. Conclusions: These findings highlight the need for pharmacogenetic screening to inform personalized medicine, diminish ADRs, and enhance the clinical care of OFCs in Sub-Saharan Africa. Full article

Background: Childhood obesity has reached epidemic levels in developed countries and is an emerging concern in developing regions. Children with excess weight are more likely to maintain this condition over time into adulthood and face a higher risk of developing metabolic disorders such as type 2 diabetes, hypertension, metabolic dysfunction-associated liver disease, and dyslipidemia. Early identification of obesity risk is, therefore, a key public health challenge. Methods: This is an observational, prospective, single-center cohort pilot study in 66 mother–infant dyads recruited at the Gynecology and Obstetrics Service of the Virgen de la Arrixaca University Hospital (Murcia, Spain). The primary objective is to identify early-life, non-invasive biomarkers associated with increased adiposity by integrating multi-omics approaches and analyzing maternal–infant interactions. Pregnant women will be enrolled during the third trimester and will undergo a baseline visit at 38 weeks of gestation for clinical and anthropometric assessment. Buccal swabs and fecal samples will be collected at baseline and in the peripartum period for epigenetic (DNA methylation), metagenomic, and metabolomic analyses. Infants will be evaluated at birth and followed at 6 months, 1 year, 2 years, and 3 years. Each visit will include detailed anthropometric measurements, along with collection of buccal swabs and fecal samples for multi-omics profiling. Conclusions: This multidisciplinary study aims to assess how maternal factors influence infant epigenetic and microbial patterns, and their relation to adiposity development. Early identification of such biomarkers may guide personalized prevention strategies and reduce the long-term burden of obesity-related comorbidities. Full article

Background/Objectives: Anterior open bite is a multifact orial malocclusion influenced by genetic and environmental factors. Variants in the Collagen type I, alpha 1 (COL1A1) gene, particularly rs1800012, have been implicated in bone quality, but their role in craniofacial anomalies remains unclear. Methods: A case–control study was conducted with 60 participants (30 anterior open bite cases; 30 matched controls). DNA was extracted from buccal swabs, and rs1800012 genotyping was performed using TaqMan assays. Genotype and allele distributions were compared with chi-square and Fisher’s exact tests; Hardy–Weinberg equilibrium was assessed in controls. Results: Genotype (GG/GT/TT: 53.3/40.0/6.7% vs. 60.0/33.3/6.7%) and allele (T allele: 26.7% vs. 23.3%) frequencies did not differ significantly between cases and controls. No association was detected under additive, dominant, or recessive models (all p > 0.05). Wide confidence intervals indicated limited precision of effect estimates. Conclusions: This study provides no evidence of association between COL1A1 rs1800012 and anterior open bite in this Turkish cohort. The relatively small sample size, the rarity of the TT genotype, and the multifactorial nature of craniofacial development represent important limitations. Larger, multi-gene, and functionally integrated studies are required to clarify the genetic architecture of open bite malocclusion. Full article

Prenatal tobacco smoke exposure (TSE) has been associated with significant alterations in DNA methylation (DNAm), an epigenetic mechanism with potential functional consequences to child development. This pilot study aimed to investigate differential DNAm patterns in preterm children with and without prenatal TSE using reduced representation bisulfite sequencing (RRBS) to interrogate a wider array of sites than in more common approaches, namely microarrays. Buccal swabs were collected from 16 two-year-old children (7 with TSE, 9 without), and DNAm was quantified at over 1.3 million CpG sites. To identify differential DNAm, univariable analyses were first performed and followed by Bayesian beta-binomial hierarchical regression models for sequence count data including adjustment for potential confounders. False Discovery Rate correction was used to account for multiple comparisons. Significant differential methylation was observed at CpG sites within intronic regions of the CALN1 and LINGO1 genes and the distal intergenic region of the TBL1XR1 gene. These findings suggest that prenatal TSE may influence epigenetic regulation in genes involved in neurodevelopment. This study demonstrates the importance of RRBS in identifying novel DNAm changes associated with prenatal TSE and highlights the need for larger studies to validate and expand upon these preliminary findings. Full article

The TT genotype of the ACTN-3 polymorphism (rs1815739) has been previously associated with lower sprinting and jumping performance, higher frequency and severity of muscle injuries and eccentric muscle damage in professional football players. This study examined the influence of rs1815739 polymorphism on maximal running speed (MRS) during official matches in elite football players. MRS was collected, using a Global Position System (GPS) at high sampling frequencies (50 Hz), from 45 footballers of the same team during 26 official matches (707 match observations). A buccal swab was used to extract genomic DNA, and an RFLP PCR technique was used to determine the ACTN-3 genotype. The main finding of the present study was that CC players showed significantly higher MRS than TT players (CC = 33.1 ± 1.3 km·h⁻¹; CT = 32.7 ± 1.6 km·h⁻¹; TT = 31.5 ± 1.9 km·h⁻¹, p = 0.041). Moreover, the players harboring a copy of the C allele showed a trend toward higher MRS than TT genotype (CC + CT = 32.9 ± 1.5 km·h⁻¹ vs. TT = 31.5 ± 1.9 km·h⁻¹, p = 0.06). We found, for the first time, an association between the ACTN-3 polymorphism and match-play MRS in elite football players. Our results bring new knowledge to the literature regarding the advantage conferred by the C allele (CC and CT genotypes) of the ACTN-3 polymorphism on sprint performance in football providing perspectives for modulating the speed training program in relation to ACTN-3 genotypes, enhancing performance avoiding muscle lesions. Full article

Background: This genetic association study investigated single nucleotide polymorphism (SNP) in interleukin-8 (CXCL8) and opiorphin (OPRPN) genes, as well as psychological characteristics and oral behaviours, between patients with pain-related temporomandibular disorders (TMDp) and healthy controls. The aim was to examine associations and predictive value of these factors for TMDp subtypes: arthralgia and myalgia. Methods: A total of 85 patients with TMDp (arthralgia and/or myalgia) and 85 pain-free controls were included. Diagnoses were established following the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). All participants completed standardised self-report questionnaires assessing anxiety, depression, and oral behaviours. Buccal swabs were collected for DNA extraction, and SNP genotyping was performed using real-time PCR. Statistical analyses were conducted using dominant and recessive genetic models. Logistic regression models were applied to assess risk factors for each TMDp subtype. Results: Participants homozygous for the minor allele (CC genotype) of rs1387964 in OPRPN were significantly more prevalent in both arthralgia and myalgia groups compared to controls. Age and female sex predicted TMDp-arthralgia. Predictors of TMDp-myalgia included the CC genotype of rs1387964, age, female sex, anxiety, and depression. Conclusions: Genetic background and psychological characteristics were significant predictors of TMDp myalgia, highlighting a multifactorial profile for this TMDp subtype. Full article

Background: Respiratory syncytial virus (RSV) bronchiolitis is a leading cause of lower respiratory tract infections in children under two years of age. NF-κB is a key transcription factor in antiviral and inflammatory responses. This study investigates the expression of NF-κB mRNA in both blood and buccal swab samples of pediatric patients hospitalized for RSV bronchiolitis, comparing levels at admission and discharge. Methods: Paired peripheral blood and buccal swab samples were collected from pediatric patients (n = 85) at hospital admission and discharge. Quantitative real-time PCR was used to assess NF-κB mRNA levels. Results: NF-κB mRNA levels significantly decreased in blood between admission and discharge (p < 0.05), while no significant change was observed in buccal swabs. Conclusions: These results suggest a compartment-specific regulation of NF-κB, with systemic inflammatory resolution at discharge and persistent or distinct mucosal immune activity. Understanding these dynamics may improve our approach to monitoring and treating RSV bronchiolitis. Full article

Leishmaniasis is a serious zoonotic parasitic disease caused by the protist Leishmania infantum and transmitted by phlebotomine sandflies in the countries of the Mediterranean basin. Dogs are the species most susceptible to the disease and serve as a reservoir for transmission to humans, making the Iberian Peninsula an endemic region for this infection. Although the regions close to the Mediterranean coast are the most prevalent regions of leishmaniasis in Spain, climatic factors are favouring the expansion of the vectors to more northern latitudes, where the disease was hardly known decades ago. This paper presents a prevalence study of L. infantum infection in the province of Zamora (northwestern Spain) using a non-invasive sample from canine buccal swabs and an innovative qPCR method to determine the etiologic agent. The parasite load of 151 randomly selected dogs from different points of the province was analysed during the period 2021–2022, with an estimated prevalence of 30%. In addition, the most common clinical signs of leishmaniasis in the dogs are described, and intrinsic factors associated with the nature of the dogs—such as sex, size, age as well as other factors related to the habitat in which they live and their geographical location—which could favour the disease, are evaluated. Full article

Third-generation sequencing (TGS), also known as long-read sequencing, has become a promising tool in clinical and research laboratories because it delivers high-resolution results with unmatched throughput. Specialised immunohematology laboratories currently employ sequencing-based methods to characterise rare ABO blood group phenotypes that cannot be identified through serology and genotyping methods. However, routine clinical application of these methods remains elusive due to the absence of validated laboratory protocols and bioinformatics tools. In this study, we have developed and validated a TGS-based workflow for comprehensive determination of the clinically relevant ABO phenotypes from DNA isolated from buccal swabs or whole blood. The region spanning exons 2 to 7 of the ABO gene were amplified and sequenced on MinION 10.4.1 flow cells. Predicted ABO phenotypes were initially determined based on single-nucleotide variants at gDNA261 (rs8176719), gDNA796 (rs8176746), and gDNA803 (rs8176747). However, certain O subtypes lacked the distinguishing deletion (rs8176719) and instead exhibited variations in exon 7 at gDNA802 (rs41302905) and gDNA805, caused by gDNA804 (rs782782485), which differentiate them from A alleles sharing the same nucleotides at gDNA261, gDNA796, and gDNA803. These additional variants were added to the analysis pipeline to identify the additional subtypes. DNA sequence data were sufficient to distinguish between the four clinically relevant ABO blood group phenotypes based on five polymorphic positions. While high sequencing coverage allowed for higher resolution genetic analysis, as few as 20 reads are sufficient for determining the ABO genotype and predicted phenotype of an individual. Typing results generated by this pipeline showed remarkable concordance with both serological results and molecular typing results by an independent laboratory, indicating its accuracy and reliability. This study demonstrates a comprehensive characterisation of clinically relevant ABO blood genotypes and predicted phenotypes using TGS methods. The approach provided a scalable and precise method for routine ABO blood group screening and aided in the development of pioneering bioinformatics tools suitable for clinical and research application. Full article

Background/Objectives: Pharmacogenetic (PGx) testing can predict drug efficacy, toxicity, and risk of adverse drug reactions (ADRs). However, PGx-guided prescribing for pediatric chronic pain is underutilized. Methods: We evaluated the rate of deviance from standard drug dosing regimens in children and adolescents with chronic pain based on PGx testing of drug-metabolizing genes. We also assessed the acceptability and feasibility of PGx testing and implementation of PGx-guided recommendations from patient, caregiver, and prescriber perspectives. Finally, we explored whether PGx results could predict self-reported therapeutic responses and/or ADRs to medications. Results: Forty-eight participants aged 8–17 years with chronic pain provided DNA via buccal swab. Genetic variant data for CYP2D6, CYP2C9, and CYP2C19 metabolism genes and associated metabolizer status were analyzed with respect to clinical PGx guidelines for dosing recommendations of analgesics and psychotropic medications. Participants, their caregivers, and their prescribers also completed quantitative questionnaires evaluating their experience with PGx testing. Twenty-three (50%) participants were predicted to benefit from non-standard dosing for medications with clinical PGx guidelines. Participants expressed satisfaction with the PGx testing process and felt it was safe and worthwhile. Prescribers also reported that PGx results were relevant for medication choices in 42 (91%) participants. Seven (15%) participants had genotyping results which may have predicted their self-reported therapeutic responses and/or ADRs to specific medications. Conclusions: Though further research on pharmacodynamic associations is required to sufficiently address the complexity of interpatient responses to medications for the treatment of pediatric pain and mental health conditions, PGx testing may be used to inform individualized medication choices based on genetic make-up. Full article

Background: Previous studies have tested the association between the COL5A1 rs12722 polymorphism and the risk of anterior cruciate ligament (ACL) injury. Overall, their results are contradictory because most studies used relatively small samples and data from ACL ruptures during sport activities have been mixed with ruptures suffered in non-sporting contexts. Objective: To examine the association between the COL5A1 rs12722 polymorphism and the prevalence of ACL rupture in a homogeneous sample of professional male football players. Methods: A total of 268 professional male football players participated in this study. The COL5A1 rs12722 genotype (CC, CT and TT) was obtained from each player using genomic DNA samples obtained from a buccal swab and measured with PCR RFLP. Players with history of ACL rupture during their professional career were identified by the medical staff of each team. Only ACL injuries obtained during football exposure were considered for this investigation. In this process, we identified 49 ACL ruptures pertaining to 43 players suffered between 2013 and 2024. The situational pattern (i.e., attacking or defending, type of football action, moment of the season, match/training exposure, etc.) was also obtained for each injury. A sub-analysis of non-contact ACL ruptures was conducted, as these injuries are more likely to be influenced by genetic factors. Results: The distribution of genotypes was similar in players with history of ACL rupture (n = 43; CC/CT/TT, 24.4/48.9/26.7%) and with no history of ACL rupture (n = 225; 25.3/49.8/24.9%; p = 0.973). Overall, the prevalence of players with history of ACL injury was 16.2% for the whole group of CC players (11 out of 68 players), 16.4% for whole group of CT (22 out of 135 players) and 15.2% for the group of TT players (10 out of 66 players; p = 0.973). However, the COL5A1 rs12722 genotype affected the dominance of the injured leg (p = 0.012), the type of action that originated the injury (p = 0.047), and the distribution of non-contact ACL injuries depending on the time of the match (p = 0.020). Specifically, CC players suffered ruptures predominantly in the dominant leg, when landing or reaching (offensive actions) and in the last 15 min of the match (all p < 0.050). On the contrary, TT players had ACL ruptures predominantly in their non-dominant leg, when pressing the opponent (defensive actions) and in the first 15 min of the match (all p < 0.050). Conclusion: There was no association between any of the COL5A1 rs12722 genotypes and the overall prevalence of ACL rupture in professional football players. However, the COL5A1 rs12722 polymorphism appeared to influence specific characteristics of the injury, such as the type of action leading to the rupture and the timing within the match, suggesting a potential genetic contribution to injury susceptibility. Full article

Animal welfare is influenced by the cumulative life experiences of an individual. Among these, exposure to chronic stressors has a significant impact on both physical and mental health, contributing to premature aging—a process linked to telomere shortening. Conversely, positive experiences have been shown to mitigate, delay, and sometimes reverse telomere attrition. This suggests that telomere length could be a reliable indicator for assessing animal welfare. This study explored the association between telomere length and characteristics such as life history, environment, and health in domestic dogs. Buccal swabs collected DNA samples from 250 dogs, and telomere length was quantified via qPCR. Our findings revealed that environmental factors significantly influenced telomere length. Dogs housed in kennels or subjected to low physical activity levels exhibited shorter telomeres. Similarly, dogs living in groups of more than five dogs had shorter telomeres, and male dogs were found to have longer telomeres than females. Overall, these results highlight the importance of environmental conditions in influencing telomere length in dogs and the potential to use this biological indicator to evaluate animal welfare. Full article

Congenital hypothyroidism (CH) is among the most common endocrine disorders in neonates. Genetic testing is essential for elucidating the underlying etiology, especially in cases of permanent CH. We enrolled 32 patients diagnosed with permanent CH from the Pediatric Endocrinology Clinics at Jeju National University Hospital and Soonchunhyang University Cheonan Hospital. Whole-exome sequencing (WES) was performed on genomic DNA extracted from buccal swabs. Variants were classified according to guidelines established by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP). WES identified 21 distinct genetic variants in 20 of the 32 patients (62.5%), spanning 6 CH-related genes: DUOX2, DUOXA2, TPO, PAX8, TG, and TSHR. Of these, 12 variants classified as pathogenic or likely pathogenic were detected in 15 patients (50%). When classified by inheritance patterns, nine patients had either homozygous (n = 1) or compound heterozygous (n = 8) variants, four patients exhibited oligogenic variants, and two patients carried a single heterozygous variant with pathogenicity. The most frequently affected gene was DUOX2, with pathogenic or likely pathogenic variants found in six patients. Notably, none of the six patients with thyroid agenesis or ectopic thyroid glands harbored detectable pathogenic variants. Our findings underscore the critical role of genetic analysis in determining the etiology of permanent CH. Whole-exome sequencing demonstrated a high prevalence of pathogenic variants, particularly in DUOX2, in Korean patients with CH. These data enhance our understanding of the genetic architecture of CH and have important implications for personalized treatment and genetic counseling. Full article

Background: Two hereditary eye disorders that are frequently observed in Collies and related breeds are Collie Eye Anomaly (CEA) and Progressive Retinal Atrophy (PRA). The main symptom of CEA is choroidal hypoplasia. It is associated with a 7.8 kb deletion in intron 4 of the NHEJ1 gene located on chromosome CFA7. Rod–cone dysplasia 3 (RCD3), an early-onset form of PRA, is associated with mutations in the PDE6A gene. Methods: Molecular diagnostic techniques were used in this study to identify genetic mutations linked to CEA and RCD3-type PRA in a subset of dog breeds. Australian Shepherds (n = 29), Border Collies (n = 9), Longhaired Collies (n = 27), and Shetland Sheepdogs (n = 10) provided a total of 75 DNA samples. Samples were collected by buccal swab or blood draw, and PCR and real-time PCR methods were used for processing. Results: Of the dogs in the studied breeds, 31 had the NHEJ1 gene mutation linked to CEA. Among these, 15 were homozygous recessive (affected), while 16 were heterozygous (carriers). None of the samples had any mutations in the PDE6A gene associated with RCD3-type PRA. Conclusions: Effective identification of carriers and affected individuals for CEA was made possible by PCR-based genetic testing, confirming its value in early diagnosis and breed control. Although the RCD3 form of PRA has not been previously reported in Collies or Australian Shepherds, it was included in our analysis due to the genetic relatedness among herding breeds and the potential presence of undetected carriers resulting from historical crossbreeding. Full article