Search Results (251)

Background/Objectives: Familial Mediterranean fever (FMF) is a chronic autoinflammatory disorder that can affect cardiac structure and function. However, the impact of different Mediterranean fever (MEFV) gene subtypes on clinical features and subclinical cardiac changes remains unclear. This study aimed to evaluate the association between MEFV gene subtypes, clinical features, and cardiac function in patients with FMF. Methods: A total of 98 patients with FMF were prospectively included. Twelve mutations in the MEFV gene were screened, and the M694V homozygous (Gene-1), M694V heterozygous (Gene-2), and M680I heterozygous (Gene-3) subtypes were analyzed. All patients underwent transthoracic echocardiography and speckle-tracking strain analysis. Results: The age of disease onset was earlier in patients carrying the gene-1 mutation compared to mutation-negative patients (11.4 ± 8.0 and 17.6 ± 11.4 years, respectively; p = 0.025). Disease duration was longer in patients with gene-1 mutation (23.3 ± 12.8 and 12.5 ± 9.3 years, respectively; p < 0.001), and disease activity score was higher (6.41 ± 1.9 and 5.15 ± 1.6, respectively; p = 0.007). Furthermore, left atrial contractile strain was significantly lower in this group (−10.6 ± 3.5% and −14.5 ± 6.1%, respectively; p = 0.012). Arthralgia was more frequent in patients with gene-2 mutation (p = 0.026), while left atrial contractile strain was better preserved compared to mutation-negative patients (p = 0.002). No significant association was found between gene-3 mutation and clinical or cardiac parameters. Conclusions: MEFV gene subtypes have different effects on clinical phenotype and cardiac function in FMF. These findings support the importance of genotype-based cardiac monitoring and risk stratification in FMF patients. Full article

Background: Metabolic syndrome (MetS) is influenced by behavioral and genetic factors, yet evidence on eating behavior patterns and related genetic polymorphisms in Central Asian populations remains limited. Aim: The aim of this study was to assess eating behaviors among adults with and without MetS and evaluate their associations with clinical indicators and ADIPOQ rs266729 and MC4R rs17782313 variants. Methods: A cross-sectional study of 200 adults (115 non-MetS, 85 MetS) was conducted using Dutch Eating Behavior Questionnaire (DEBQ), standardized clinical measurements, and PCR-RFLP genotyping. Results: Participants with MetS were older than non-MetS adults (52 vs. 47 years; p = 0.004) and had substantially higher systolic blood pressure (126 vs. 114 mmHg; p < 0.001), diastolic blood pressure (83 vs. 74 mmHg; p < 0.001), and BMI (32.2 vs. 25.9 kg/m²; p < 0.001). Waist circumference, hip circumference, triglycerides, total cholesterol, and LDL were also significantly higher, while HDL was lower (1.13 ± 0.40 vs. 1.58 ± 1.50 mmol/L; p = 0.008). DEBQ restrained, emotional, and external eating scores showed no differences between groups (all p > 0.05). Eating behavior distribution was similar (p = 0.291). ADIPOQ genotypes (CC/CG/GG) did not differ by MetS status (p = 0.227), nor did MC4R variants (p = 0.679). Among MetS participants, clinical indicators did not vary across eating behavior categories, and no associations were observed between eating behavior and either polymorphism. Conclusions: Despite clear clinical and metabolic differences between MetS and non-MetS groups, neither eating behavior patterns nor ADIPOQ and MC4R variants were associated with metabolic measures among MetS group. Full article

Background/Objectives: Early-onset inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), frequently presents with a more severe clinical course. Genetic susceptibility, particularly involving the TGF-β signaling pathway, plays a key role in IBD pathogenesis. SMAD3 and LTBP3 encode crucial components of this pathway and have been implicated in IBD in previous genome-wide association studies. Methods: This study aimed to assess the clinical significance of the rs17293632 (SMAD3) and rs11545200 (LTBP3) polymorphisms in a pediatric IBD cohort. A total of 286 children (133 with UC and 153 with CD) were recruited from seven pediatric centers in Poland. Clinical data included age at diagnosis, inflammatory markers (CRP, albumin), growth indices (Z-scores for weight, height, and BMI), and treatment regimens. Results: The LTBP3 rs11545200 minor allele was significantly associated with a younger age at diagnosis, poorer nutritional status during disease flares, and a more frequent use of infliximab—particularly in patients with UC. In CD, the SMAD3 rs17293632 major homozygous genotype was associated with increased use of systemic corticosteroids, suggesting a more severe or treatment-resistant disease phenotype. Conclusions: The assessed polymorphisms in LTBP3 and SMAD3, both involved in TGF-β signaling, are associated with clinical characteristics of pediatric IBD. These findings support the potential role of genetic variants as biomarkers for disease severity and treatment tailoring, contributing to the development of personalised therapeutic strategies in children with IBD. Full article

Background: Impulsivity is a multidimensional trait associated with the development and maintenance of behavioral and substance addictions. Genetic polymorphisms, particularly within the dopaminergic system, are thought to modulate individual differences in impulsivity. The COMT rs4680 (Val158Met) polymorphism influences enzymatic activity of catechol-O-methyltransferase and may alter dopaminergic tone in the prefrontal cortex. This study investigated whether COMT rs4680 genotype interacts with addiction status (behavioral and substance addictions) to influence trait impulsivity. Methods: The study included 309 Polish men: 128 with mixed behavioral and substance addictions and 181 healthy controls. All participants completed the Barratt Impulsiveness Scale (BIS-11) and were genotyped for COMT rs4680. A two-way ANOVA was used to assess main and interaction effects of genotype and group on total and subscale BIS-11 scores. Results: Individuals with mixed addictions scored significantly higher on all BIS-11 subscales (p < 0.01). A significant interaction effect was observed for the Non-Planning (F_2,303 = 4.40, p = 0.0131, η² = 0.028) and Total BIS-11 scale (F_2,303 = 5.77, p = 0.0035, η² = 0.037), with the A/A genotype associated with increased impulsivity, especially among the clinical group. Conclusions: These findings support a gene-by-environment interaction in impulsivity, where COMT rs4680 Met/Met homozygotes may be more susceptible to heightened impulsivity in addiction contexts. The results highlight the potential utility of COMT genotyping in personalizing therapeutic strategies for impulse-related disorders such as addictive disorders. This study extends evidence on dopaminergic modulation of impulsivity to behavioral and substance addictions. Full article

This study examines the effectiveness of machine learning approaches for the automatic identification of watermelon genotypes from the seeds of watermelon, for the snack-type watermelon (Citrullus lanatus). Nine genotypes with red, white, and black seed coats were assessed in total. For each genotype, 200 seeds were analyzed using high-resolution imaging and digital measurement techniques for the extraction of morphological characteristics (length, width, thickness, area, perimeter, equivalent diameter, etc., and physical (weight) and colorimetric attributes of the (L, a, b). The resulting dataset was modeled using Artificial Neural Network (ANN), Random Forest (RF) and Extra Tree (ET) algorithms and performance was validated by a 10-fold cross-validation. The primary objective of the study was to match (identify) each seed accurately with its respective genotype by using the morphological, physical, and colorimetric characteristics of the seed and thus to perform genotypic classification. The comparative results showed that the RF model had the highest genotypic performance (accuracy 92.22%, F1-score 91.87%, Cohen’s Kappa 0.9118), followed by the ET (accuracy, 90.00%) and ANN models with a relatively lower precision (86.11%). Statistical analysis using the Wilcoxon signed-rank test confirmed that both RF and ET significantly outperformed ANN, with RF providing superior balance and stability over ET. The findings highlight that machine learning-based frameworks enable rapid, reliable, and non-destructive classification (identification) of snack-type watermelon seeds according to their genotypes. Such approaches hold strong potential for enhancing varietal traceability in breeding programs, improving quality control in commercial seed production, and meeting the high-throughput demands of seed processing industries. Full article

Background: Venous thromboembolism (VTE) is a multifactorial disorder influenced by both genetic and environmental factors, with substantial variability in susceptibility across populations. Data on VTE-associated genetic variants in Asian populations, including Thais, remain limited. To address this, we developed a 39-single-nucleotide polymorphism (SNP) genotyping panel using the MassARRAY platform and evaluated its association with VTE in a Thai cohort. Methods: A total of 209 individuals, comprising 122 patients with objectively confirmed VTE and 87 age- and sex-matched healthy controls, were genotyped. Allele frequencies were compared, and associations with VTE were assessed. Results: Seven SNPs demonstrated significant associations: five risk alleles (PROC rs146922325, ABO rs8176743, FGG rs2066865, F11 rs4253417, and HIVEP1 rs169713) and two protective alleles (F5 rs4524 and TGFB2 rs57615042). To examine cumulative effects, a polygenic risk score (PRS) integrating genetic and clinical factors was constructed. Higher PRS was significantly associated with recurrence, particularly among patients with unprovoked VTE, conferring more than a threefold increase in recurrence risk (HR = 3.53, 95% CI: 1.04–10.2, p = 0.043). These findings provide the first systematic evidence of population-specific genetic risk factors for VTE in Thais and highlight the clinical potential of PRS for recurrence prediction. Conclusions: The MassARRAY-based panel offers a cost-effective, high-throughput strategy for simultaneous SNP detection, supporting scalable genomic studies and personalized risk stratification. Our results contribute to understanding the genetic architecture of VTE and highlight the value of incorporating non-European populations into genetic studies to advance precision medicine. Full article

Background/Objectives: Arterial stiffness increases with progressive worsening of renal function and predicts cardiovascular mortality in patients with chronic kidney disease. The effects of vitamin K-dependent proteins in vascular health and the implications of vitamin K epoxide reductase gene (VKORC1) polymorphisms in calcification and warfarin sensitivity are well known, but their roles in arterial stiffness are not known. We investigated the influence of common polymorphisms in this gene (−1639G>A, +1173C>T, +1542G>C, +2255C>T, and +3730G>A) on stiffness and calcification markers in 302 CKD patients. Methods: Blood pressure, aortic pulse wave velocity (aPWV), coronary artery calcification (CAC), and aortic calcification (AC) were assessed together with the total uncarboxylated matrix Gla protein (t-uncMGP). Results: Genotyping subjects for +1542G>C and +3730G>A showed higher genotype-specific aPWV and lower t-uncMGP (p < 0.05). The combined recessive allele model showed a significant stepwise reduction in aPWV (p < 0.005); subjects homozygous for both risk alleles had the highest aPWV compared to those carrying one or none. In a multiple regression model adjusting for age, gender, mean pressure, BMI, and racial group, each +1542G allele and +3730A allele were independently associated with a 0.8 m/s (95% CI 0.09 to 1.57) and 1.0 m/s (95% CI 0.14 to 1.98) elevation of aPWV, respectively. Although serum t-uncMGP levels correlated inversely with CAC score (p < 0.001), VKORC1 genotypes did not. Conclusions: We demonstrated for the first time that VKORC1 polymorphisms (+1542G>C and +3730G>A) influence arterial stiffness and serum t-uncMGP levels in CKD patients. These findings suggest that vitamin K-dependent processes may be important in arterial stiffness, possibly by modulating calcification of the vessel wall. Full article

Background and Objectives: The dopamine D2 receptor (DRD2) plays a central role in fronto-striatal circuits regulating cognitive control and reward processing. The rs1076560 polymorphism alters receptor isoform expression, potentially modifying impulsivity and vulnerability to stimulant use disorders. We examined gene–environment interactions between rs1076560 and stimulant dependence in relation to impulsivity, ADHD traits, and hedonic capacity. Methods: A total of 517 men (235 stimulant-dependent, 282 controls) completed the Barratt Impulsiveness Scale (BIS-11), Adult ADHD Self-Report Scale (ASRS v1.1), and Snaith–Hamilton Pleasure Scale (SHAPS). Genotyping for rs1076560 was performed using real-time PCR, and two-way ANOVAs tested genotype-by-group effects. Results: Significant genotype-by-group interactions were observed across all BIS-11 subscales and ASRS scores. In the stimulant-dependent group, C/C homozygotes showed the highest levels of attentional impulsivity and attentional dysregulation compared to both A/C and C/C controls. In contrast, within the control group, A/A homozygotes demonstrated higher motor impulsivity, non-planning impulsivity, and BIS-11 total scores than C/C controls. No significant main effects or interactions were found for SHAPS scores. Conclusions: DRD2 rs1076560 moderates impulsivity-related traits through dopaminergic pathways relevant to executive dysfunction in stimulant use disorders. These findings highlight a neurobiological mechanism of addiction vulnerability and may inform precision approaches in neurology and psychiatry. Full article

The development of grapevine varieties combining powdery mildew (Erysiphe necator) resistance with acceptable wine quality represents an important goal for sustainable viticulture. This study evaluated the oenological potential of five advanced breeding lines carrying Run1 or Run1Ren1 resistance loci, developed through marker-assisted selection to achieve 99.2–99.6% Vitis vinifera genome content. Genotypes were assessed under Chilean conditions during the 2024–2025 seasons, analyzing disease resistance, berry characteristics, and wine chemical parameters. All resistant genotypes exhibited complete powdery mildew resistance (OIV scores 9) without fungicide applications. Wine analyses showed pH 3.4–3.9, titratable acidity 3.7–7.8 g/L, and total phenolics 229.2–1356.1 mg GAE/L, values within ranges reported in the literature for commercial wines. Two genotypes evaluated across both seasons showed different patterns of year-to-year variation, with AJ-T2 showing 4.7% variation in anthocyanin content, while AJ-T6 exhibited greater variation in phenolic parameters. HPLC analysis revealed anthocyanin profiles dominated by malvidin-3-glucoside without diglucoside forms, consistent with V. vinifera patterns. These preliminary results from single-plant evaluations suggest that marker-assisted breeding may contribute to developing disease-resistant varieties with wine chemical parameters within commercial ranges, though multi-plant trials with appropriate controls are essential for validation. Full article

Background: Treatment failure continues to play a role in HIV-related morbidity in Mozambique. Antiretroviral therapy (ART) regimen switches are decided empirically, as HIV genotypic resistance testing (HIV-GT) is unavailable in Mozambique’s public health system. Since 2016, Médecins Sans Frontières (MSF) and I-TECH have provided access to HIV-GT at Alto Maé Health Center, Maputo. We describe the cohort of people with virologic failure (VF) that underwent HIV-GT and analyze dolutegravir (DTG) resistance (R) patterns. Methods: This cross-sectional assessment of routine programmatic data between July 2020 and February 2024 was conducted to guide future program enhancements. People living with HIV (PLWH) receiving ART beyond the first line with confirmed VF were included. Mutations were interpreted according to the Stanford HIVdb algorithm. We applied Bayesian bootstrapping for analysis, and the threshold for significance of effects was defined as a probability of 95%. Results: A total of 106 persons underwent HIV-GT following a structured adherence strategy, 62 (58.5%) of whom were on a DTG-based regimen. Fifty-seven of the 62 samples from persons on a DTG-based regimen were sequenced, and 51 (89.5% [95% CrI: 80.7, 96.2]) had confirmed resistance to DTG; the mean DTG-R score was 70.2 (95% CrI: 62.2, 78). Samples with DTG-R had a median of three INSTI mutations (IQR 1–4). Major DTG-associated mutations were found in 46 out of 57 samples: G118R (n = 28), R263K (n = 15), and Q148RK (n = 7). None of the people on the protease inhibitor regimen had an INSTI mutation. Conclusions: In contexts with limited access to resistance testing, the introduction of algorithms to identify PLWH at risk of developing drug resistance is strongly recommended. The proposed algorithm incorporates adherence reinforcement strategies, as recommended in national policies, followed by a short, supervised antiretroviral therapy (ART) support strategy. This approach has shown a high predictive value for identifying PLWH with resistance mutations to dolutegravir (DTG), thereby allowing the continuation of the effective DTG regimen without unnecessary regimen switches. Full article

Understanding trait relationships is fundamental in soybean breeding because the goal is to maximize simultaneous gains. Standard multi-trait genome-wide association studies (MT-GWAS) identify variants linked to multiple traits but fail to capture phenotypic structures or interrelations. Structural Equation Models (SEM) account for covariances and recursion, enabling the decomposition of single nucleotide polymorphism (SNP) effects into direct or indirect components and identifying pleiotropic regions. We applied SEM to analyze morphology (pod thickness, PT) and yield traits (number of pods, NP; number of grains, NG; hundred-grain weight, HGW). The dataset comprised 96 soybean individuals genotyped with 4070 SNP markers. The phenotypic network was constructed using the hill-climbing algorithm, a class of score-based methods commonly applied to learn the structure of Bayesian networks, and structural coefficients were estimated with SEM. According to coefficient signs, we identified negative interrelationships between NG and HGW, and positive ones between NP and NG, and HGW and PT. NG, HGW, and PT showed indirect SNP effects. We also found loci jointly controlling traits. In total, 46 candidate genes were identified: 7 associated exclusively with NP and 4 associated with NG. An additional 15 genes were common to NP and NG, 3 were common to NP and HGW, 6 were common to NG and HGW, and 11 were common to NP, NG, and HGW. In summary, SEM-GWAS revealed novel relationships among soybean traits, including PT, supporting breeding programs. Full article

Hypothyroidism is a multifactorial endocrine disorder where genetic predisposition plays a significant role. The MTHFR, MTRR, and MTR genes influence thyroid hormone regulation via homocysteine remethylation and DNA methylation. This study examined associations between hypothyroidism and polymorphisms in MTHFR (C677T–rs1801133, A1298C–rs1801131), MTRR (A66G–rs1801394), and MTR (A2756G–rs1805087) genes. Eighty-six patients with hypothyroidism and 87 healthy controls were included. Genotyping was performed using PCR-RFLP. Post hoc analysis confirmed adequate statistical power (95% for MTRR A66G, 84.6% for MTR A2756G). The study adhered to STROBE guidelines. MTHFR polymorphisms showed no significant association when considered individually. However, the MTRR A66G AA genotype was significantly more frequent in patients and conferred a markedly increased disease risk (OR: 4.373; 95% CI: 2.174–8.797; p < 0.001), while the MTR A2756G AG genotype was also more prevalent among patients and associated with higher susceptibility (OR: 2.178; 95% CI: 1.156–4.104; p = 0.008). Genotype combination analysis revealed that CT–AA (OR = 6.898; 95% CI: 1.941–24.516; p = 0.001) and AG–AA (OR = 6.892; 95% CI: 1.494–31.797; p = 0.007) conferred high risk. Certain genotypes correlated with clinical features, including hypercholesterolemia, diabetes, and cardiovascular disease. MTRR A66G and MTR A2756G polymorphisms are associated with hypothyroidism and metabolic comorbidities, both individually and in genotype combinations. These findings underscore the value of multilocus genetic models for understanding thyroid disorders and support the potential role of genetic biomarkers in personalized risk assessment and early diagnosis. GRS analysis demonstrated that each additional risk allele increased hypothyroidism risk (OR = 1.58; 95% CI: 1.18–2.10; p = 0.0018), and the total score showed moderate predictive power (AUC = 0.665; p < 0.001). Full article

Exogenous histamine obtained from the intake of histamine-rich food is mainly metabolized by the diamine oxidase enzyme (DAO). Histamine intolerance (HIT) is an alteration mainly caused by DAO deficiency, which is commonly associated with gastrointestinal, respiratory, cardiovascular, central nervous system, muscular, skeletal, and skin symptoms. Despite four single-nucleotide polymorphisms (SNPs) being mainly associated with DAO deficiency, the probability of inheriting these variants and their relationship with HIT in the Mexican population remain unknown. Objective: The aim of this study was to evaluate the prevalence of these SNPs and their relationships with HIT in the Mexican population, including both individual volunteers and family groups. Methods: Four SNPs related to DAO deficiency were detected in 112 volunteers; medical questionnaires were answered. Results: The prevalence of genetic DAO deficiency attributed to at least one risk allele was 78.57% (rs1049793 was the main SNP). Fifteen DAO SNP combinations were detected (the main rs2052129, rs10156191, rs1049742 (wild-type homozygotes), and rs1049793 (heterozygote), 31.25%). A total of 41.07% of the volunteers presented at least three symptoms in different systems related to HIT, of whom 84.78% presented at least one SNP. The DAO deficiency genetic risk score varied among individual volunteers and families. The highest probability of having a mutated homozygote was 11.8% (rs1049793). HIT symptoms varied among relatives sharing identical genotypes. Conclusions: The prevalence of SNPs related to DAO deficiency in the Mexican population correlates with globally reported data; however, further analysis with volunteers distributed throughout the country would be desirable. Although genetic predisposition was common, the presence of SNPs alone did not predict specific HIT symptoms. Multiple SNPs may increase the presence of HIT symptoms, regardless of the type of allele. These findings highlight the multifactorial nature of HIT and underscore the need for standardized diagnostic criteria. Full article

Background/Objectives: Schizophrenia (SCZ) is a highly heritable mental disorder with a complex polygenic genetic architecture. The heat shock protein 90 alpha (HSP90α), encoded by the HSP90AA1 gene, is a molecular chaperone that is required for the proper folding and activity of many of the client proteins that are involved in numerous essential cellular pathways. In addition to its general chaperone activity, HSP90α plays a role in other neuronal contexts and was found to have an altered expression in SCZ, which makes HSP90AA1 an attractive gene for association studies. The aim of this study was to determine whether the HSP90AA1 polymorphisms (rs8005905, rs10873531, rs11621560, rs4947 and rs2298877) are involved in the risk of developing SCZ and its clinical picture in a Polish Caucasian population. Methods: A total of 1088 unrelated subjects (409 patients and 679 healthy controls) were included in the study. The SNPs were genotyped using a TaqMan 5′-exonuclease allelic discrimination assay. The results of the Positive and Negative Syndrome Scale (PANSS) were presented in the five-dimensional model. Results: None of the SNPs were associated with a predisposition to developing SCZ in either the single-marker or haplotype analysis including the results of gender-stratified analyses. However, the genotypes of rs11621560, rs4947 and rs2298877 SNPs were associated with the emotional distress (EMO) dimension score. Conclusions: The results of the present study indicate that HSP90AA1 variants may have an impact on the psychopathology of SCZ, although larger studies are needed to clarify these findings. Full article

Background/Objectives: Personality traits influence motivation, self-regulation, and adaptation in high-performance sports, and are partially modulated by dopaminergic genetic variability. This study aimed to examine the association between the DRD2 Ex8 rs6276 polymorphism and NEO Five-Factor Inventory (NEO-FFI) personality traits in elite athletes and non-athlete controls. Methods: A total of 323 participants were included: 141 athletes and 182 controls. Genomic DNA was isolated from venous blood, and DRD2 Ex8 rs6276 genotypes (A/A, A/G, G/G) were determined using real-time PCR with melting-curve analysis. Personality traits were assessed using the NEO-FFI, and group differences as well as genotype × group interactions were evaluated using multivariate analyses and non-parametric tests. Results: Athletes scored significantly higher on Conscientiousness than controls. A genotype × group interaction was observed for Extraversion, and the main effect of the genotype was found to be Agreeableness. Athletes with the A/A genotype exhibited the highest Extraversion scores, whereas those with the G/G genotype demonstrated higher Agreeableness than other genotypes. Conclusions: These findings indicate that dopaminergic variation contributes to individual differences in social and motivational traits, which may support athletic engagement and adaptation to high-demand environments. The results should be interpreted with caution due to the moderate sample size, deviation from the Hardy–Weinberg equilibrium in the athlete group, and reliance on a single personality assessment tool. Full article