Search Results (5,584)

Acute renal allograft rejection (AR) is immune-mediated. Recent evidence highlights some microRNAs as immune modulators. Few and conflicting studies have studied the impact of the MIR146A gene single-nucleotide polymorphism rs2910164 (C>G) on AR. We explored the association of rs2910164 with AR in a single-center cohort of 533 kidney transplant recipients (KTRs) by genotyping cases with biopsy-proven late AR (AR group, n = 35) and matched control KTRs without AR (non-AR group, n = 60). Genotyping was performed with real-time PCR. Multivariable logistic regression and Firth penalized logistic regression, as a sensitivity analysis, were used to adjust for confounding factors. Donor–recipient age difference was significantly higher in the AR group than in the non-AR group (23.37 ± 11.29 vs. 14.83 ± 10.54, p < 0.001). Recipient mean age in the AR group is lower than in the non-AR group (27.51 ± 10.34 vs. 32.83 ± 9.76 years, p = 0.014), while the opposite is observed with the donor mean age (49.57 ± 10.37 vs. 43.27 ± 10.27 years, p = 0.005). AR was associated with preformed donor-specific antibodies (DSAs) (45.7% vs. 8.3%, p = 0.000, OR = 9.263, 95% CI (2.988–28.720)), and with two HLA/A* mismatches (17.1% vs. 3.3%, p = 0.048, OR = 6.000, 95% CI (1.139–31.595)). Moreover, post-transplant viral infections, particularly with CMV and SARS-CoV-2, were associated with AR (p < 0.05). However, rs2910164 was not associated with AR across all the tested genetic models (p > 0.05). Our study provides population-specific negative association data on rs2910164 and AR. Larger multicentric studies and future meta-analyses are needed to clarify whether any effect is modest or context-dependent. Full article

Background: Cancer-associated cachexia (CAC) is a multifactorial syndrome driven by a profound metabolic and inflammatory dysregulation. Due to the central role of the insulin-like growth factor 1 (IGF-1) pathway in regulating muscle mass, energy metabolism, and inflammation, this study evaluated the relevance of five IGF-1 axis-related single-nucleotide polymorphisms (SNPs), namely IGF1 rs6220, insulin-like growth factor 1 receptor (IGF1R) rs2016347 and rs2684788, growth hormone receptor (GHR) rs6873545, and insulin receptor substrate 1 (IRS1) rs1801278. Methods: The impact of these variants on CAC onset and overall survival (OS) was assessed in a cohort of 140 cancer patients. Results: While overall-cohort analyses did not reach statistical significance, exploratory analyses suggested potential associations between the IGF1 rs6220 GG and GHR rs6873545 CC genotypes and increased CAC risk in male patients. A trend for higher CAC prevalence was also noted in younger patients (<63 years) with the rs6873545 CC genotype. For pre-CAC and CAC patients, exploratory subgroup analyses on patients’ OS were conducted following no significant results in the overall cohort. Among older patients and those with high prognostic nutritional index (PNI; >44.2), the IGF1 rs6220 G allele was associated with longer OS. Conversely, the IGF1R rs2016347 G allele and rs2684788 T allele were linked to poorer OS across multiple pre-CAC and CAC subgroups. The effects of GHR rs6873545 varied across subgroups, suggesting context-dependent activity. Conclusions: This study highlights the functional heterogeneity of IGF-1 axis-related genetic variants, indicating potential to serve as predictors of CAC. Given the exploratory nature of these findings, validation in larger cohorts is required to confirm the associations found. Full article

Knowledge of population structure and genetic relationship among inbred lines is essential for exploiting heterosis in maize breeding programs. This study evaluated the concordance between 25k Illumina^® Infinum Maize SNP (Single Nucleotide Polymorphism) Array (25k SNP array)-derived and ribonucleic acid (RNA)-sequencing (seq)-derived markers in estimating genetic relatedness and population structure within the Maize Research Institute “Zemun Polje” (MRIZP) breeding program. A panel of 28 elite MRIZP maize inbred lines, along with two public lines, was analyzed. For the RNA-seq data, three alternative SNP datasets were generated based on heterozygous-site handling (ALL, HOM, and FINAL) to assess their impact on downstream genetic inference. These approaches had distinct effects on clustering resolution and genetic relationship structure. The FINAL dataset, in which heterozygous positions were recoded as missing values and re-filtered, was selected as the most balanced dataset for comparative analyses with 25k SNP array data. Only a limited number of overlapping SNP positions were identified between RNA-seq and 25k SNP array datasets (six in ALL, two in FINAL, and none in HOM), all located within coding regions. Despite this minimal overlap, distance-based analyses revealed partial concordance in genetic relationship patterns and population structure between platforms. Genetic distances estimated from 25k SNP array markers were consistent with pedigree records and provided more informative insights than pedigree data alone. Population structure inferred from 25k SNP array data showed high concordance with previously defined heterotic groups, correctly assigning 29 out of 30 lines (96.67%) to their expected clusters. In contrast, RNA-seq-derived SNPs showed moderate concordance with expected heterotic groupings (56.67%), indicating that transcriptome-derived markers capture part of the underlying breeding structure, but do not fully resolve heterotic group separation. Overall, these results support the 25k SNP array as a robust tool for assessing genetic relatedness and population structure in maize breeding programs, while RNA-seq-derived SNPs provide complementary but less reliable information for routine heterotic assignment. Full article

The aim of the work was to identify the features of associations of single nucleotide polymorphisms (SNPs) that determine the level of sex hormones in the body with simple endometrial hyperplasia without atypia (EnH_s) in women with different body mass index (BMI). Two groups of BMI-differing subjects (BMI < 25 [n = 766]: 196 EnH_s, 570 control and BMI ≥ 25 [n = 727]: 324 EnH_s, 403 control) with a total number of 1493 women were formed to conduct this study. Nine SNPs meaningful for the level of sex hormones (proven in genome-wide association studies [GWAS]) such as rs34670419 [G>T] ZKSCAN5, rs148982377 [T>C] ZNF789, rs11031002 [T>A] FSHB, rs11031005 [T>C] FSHB, rs112295236 [C>G] SLC22A10, rs117145500 [A>C] CHD9, rs727428 [C>T] SHBG, rs1641549 [C>T] TP53, rs117585797 [C>A] ANO2 were considered by us. In general, in the studied sample (EnH_s/control, n = 1493), an association of interactions of rs148982377 [T>C] ZNF789 × BMI with EnH_s (OR = 1.11) was revealed. As a result of a comparative analysis, we found that rs148982377 [T>C] ZNF789 was associated with EnH_s in women with a BMI ≥ 25 (OR = 1.77) and was not linked with the disease in women with a BMI < 25. Both common protective factors for EnH_s were also identified in women with BMI ≥ 25 and BMI < 25 (rs11031002 [T>A] FSHB (OR = 0.43 and OR = 0.46 respectively) and rs11031005 [T>C] FSHB (OR = 0.46 and OR = 0.58 respectively)). At the same time, in the BMI ≥ 25 cohort, the risk effect of the TT*rs11031002-rs11031005 haplotype (OR = 3.27) was more pronounced, and the contribution of interlocus interactions of sex hormone genes with EnH_s formation was more significant (7 SNPs in 12 models) than in the BMI < 25 group (OR = 2.31 and 4 SNPs in 3 models). In conclusion, the presented work is exploratory and demonstrates differences in the nature of the association with EnH_s in women with different BMI of the testosterone-determining polymorphism: SNP rs148982377 [T>C] ZNF789 was associated with EnH_s in women with a BMI ≥ 25 and was not linked with the disease in women with a BMI < 25. Full article

Background/Objectives: The objective of this study is to evaluate whether maternal genetic variants previously associated with gestational duration in European-ancestry populations are associated with gestational duration in Japanese women. Methods: We analyzed 347 women with a history of delivery from a community-based cohort in Aomori Prefecture, Japan. Gestational age at first delivery (weeks) was obtained from the Maternal and Child Health Handbook. Four representative maternal single-nucleotide polymorphisms were analyzed: rs2946169 near EBF1, rs2955117 in/near EEFSEC, rs12037376 in/near WNT4, and rs9861425 in/near ADCY5. Maternal genotype data were obtained from existing Japonica Array data generated as part of the Iwaki Health Promotion Project. Associations with gestational age at first delivery were tested using linear regression under an additive genetic model, adjusted for maternal age at first delivery. A Bonferroni-corrected threshold of p < 0.0125 was applied for four SNPs. Results: Mean gestational age at first delivery was 39.4 weeks. Each additional rs2946169 T allele was nominally associated with shorter gestation (adjusted β = −0.2679 weeks per allele; p = 0.021), but this association did not remain significant after Bonferroni correction. No significant associations were observed for rs2955117, rs12037376, or rs9861425. Conclusions: These findings provide suggestive evidence that maternal variation at the EBF1 locus may be related to gestational duration in Japanese women. However, the association did not remain significant after multiple-testing correction, and larger studies are needed to confirm this finding and clarify population-specific genetic effects. Full article

Computer-assisted sperm analysis was conducted to phenotypically and genetically assess the sperm motility traits of Jinding drakes. The phenotypic evaluation revealed moderate variability across motility parameters, consistent with a polygenic inheritance pattern. Correlation analysis further demonstrated strong associations among velocity-related traits and inverse relationships between linearity and lateral head displacement metrics. Genome-wide association studies identified 15 significant single-nucleotide polymorphisms (SNPs) associated with five key sperm motility traits (straight-line velocity, curvilinear velocity, average path velocity, amplitude of lateral head displacement, and mean angular displacement) at a genome-wide threshold of p < 1 × 10⁻⁶. Notably, of these 15 SNPs, nine were concentrated on chromosome 1, indicating the presence of a genomic hotspot for regulation of sperm motility. Pleiotropic effects were evident, as several SNPs were found to influence multiple motility traits. Candidate genes implicated in essential sperm functions included Myo16 (cytoskeletal dynamics), Cep76 (flagellar structure), and Jarid2 (epigenetic regulation during spermatogenesis), as well as genes involved in membrane integrity, mitochondrial function, and immune regulation. These findings provide novel insights into the genetic architecture underlying sperm motility of Jinding drakes and establish a basis for molecular breeding strategies to enhance reproductive efficiency of waterfowl. Full article

Background: Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus with a strong genetic component. The aldo-keto reductase family 1 member B (AKR1B1) gene has been implicated in hyperglycemia-induced renal damage. This study aimed to investigate the association between AKR1B1 variants and DN through a genetic association study (GAS) and a comprehensive meta-analysis. Methods: A case–control study was conducted in a Greek population, including 190 DN patients, 150 T2DM patients without nephropathy, and 238 healthy controls. Five tagging single-nucleotide polymorphisms (SNPs) in AKR1B1 were genotyped. Associations were assessed using the generalized odds ratio (OR_G). A systematic literature search was performed, and eligible studies were included in a meta-analysis using a random-effects model. Results: In the case–control study, none of the examined SNPs showed a significant association with DN in any comparison model. However, meta-analysis results demonstrated a significant association for the promoter variant −106 C>T (rs759853) in diabetic individuals without nephropathy versus DN cases (OR_G = 1.389, 95% CI: 1.134–1.700). The (CA)n polymorphism showed a non-significant overall effect but was associated with increased risk in subgroups of Asians (OR_G = 1.455, 95% CI: 1.042–2.032) and T2DM patients (OR_G = 1.357, 95% CI: 1.039–1.771). No associations were observed when healthy controls were used. Conclusions: While no significant associations were detected in the single-cohort analysis, meta-analytic evidence supports a role of regulatory AKR1B1 variants in DN susceptibility. These findings highlight the importance of control selection and suggest that AKR1B1 may influence progression to nephropathy rather than diabetes risk per se. Full article

Background and Objectives: Non-traumatic osteonecrosis of the femoral head (ONFH) is a multifactorial disorder influenced by both environmental and genetic factors. The nuclear receptor subfamily 3 group C member 1 (NR3C1) gene encodes the glucocorticoid receptor, which plays a key role in bone metabolism, vascular regulation, and stress response. This study aimed to investigate the association between NR3C1 polymorphisms and susceptibility to ONFH, with particular emphasis on age-related genetic effects. Materials and Methods: A hospital-based case–control study was conducted using genotyping data from the Taiwan Biobank version 2 (TWBv2) custom array. A total of 609 patients with ONFH and 2436 age- and sex-matched controls were included. Forty-nine single-nucleotide polymorphisms (SNPs) within or near the NR3C1 gene with a minor allele frequency greater than 5% were analyzed. Logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) under multiple genetic inheritance models. Age-stratified analyses were also performed. Results: Among the analyzed SNPs, rs28593206 and rs315199 demonstrated nominally significant differences in allele distributions between cases and controls (p = 0.024 and p = 0.009, respectively), with minor alleles showing nominal associations with increased odds of ONFH. Additional exploratory analyses under different genetic models identified several SNPs with nominal associations with ONFH susceptibility, while rs7709864 showed a possible nominal protective association. In age-stratified analyses, several SNPs showed nominal associations with ONFH risk among individuals older than 40 years, whereas no nominally significant associations were observed in younger individuals. Conclusions: This exploratory study suggests that NR3C1 polymorphisms may be nominally associated with susceptibility to ONFH, particularly among individuals older than 40 years. However, because no formal correction for multiple comparisons was performed and detailed etiological data were unavailable, these findings should be interpreted cautiously and regarded as hypothesis-generating rather than clinically applicable evidence. Further studies incorporating larger cohorts, etiological stratification, multiple-testing correction, replication analyses, and functional validation are required to confirm these observations and clarify the underlying biological mechanisms. Full article

Sweet cherry (Prunus avium L.) is an economically important fruit species with considerable genetic variability, particularly among autochthonous cultivars. This study aimed to evaluate the genetic diversity and population structure of six indigenous sweet cherry cultivars from the Ohrid region in North Macedonia using whole-genome resequencing. A total of approximately 2.27 million single-nucleotide polymorphisms (SNPs) and 263 thousand insertions and deletions (InDels) were identified, indicating high genomic variability. Population structure and phylogenetic analyses revealed two distinct genetic clusters among the studied cultivars. The Ohridska bela cultivar showed the highest level of genetic differentiation, highlighting its importance as a valuable genetic resource. Functional annotation of genetic variants demonstrated significant variability in genes associated with flowering time, dormancy, and stress response, suggesting adaptation to local environmental conditions, while genes related to fruit ripening were highly conserved. Additionally, the rapid linkage disequilibrium decay confirmed the high genetic diversity within the population. These findings emphasize the importance of Macedonian autochthonous sweet cherry germplasm for breeding programs, conservation efforts, and future adaptation to changing environmental conditions. Full article

Phosphoglycerate kinase (PGK) is a vital glycolytic enzyme that provides energy and carbon skeletons to support fatty acid synthesis. However, the PGK gene family has not been characterized in soybean (Glycine max), and its role in soybean oil accumulation remains unclear. Here, we identified six GmPGK genes in soybean, all of which encode proteins containing conserved PGK domains. Phylogenetic analysis clustered soybean PGK proteins into three groups. Analysis of GmPGK promoters revealed relatively abundant cis-elements related to plant growth, development, and phytohormone response. Expression profiling showed that GmPGK5 transcript abundance increases progressively with oil accumulation during seed development, and is significantly higher in the high-oil variety NN1138-2. Overexpression of GmPGK5 significantly increased total fatty acid content in soybean hairy roots. A single nucleotide polymorphism (SNP) located at Chr15:49447855 within the GmPGK5 promoter was significantly associated with both seed oil content and seed weight in natural soybean accessions. Based on this SNP, a derived cleaved amplified polymorphic sequence (dCAPS) marker was developed to facilitate soybean molecular breeding. Our findings suggest that GmPGK5 may positively regulate fatty acid accumulation in soybean. The identified natural variation and dCAPS marker provide potential valuable tools for marker-assisted selection to improve soybean oil content and seed weight. Full article

Epidemiological and biological evidence indicate a close connection between Alzheimer’s disease (AD) and type-2 diabetes mellitus. Glucose transporter 1 (GLUT1), encoded by the SLC2A1 gene, has a major role in glucose metabolism, the dysregulation of which has been implicated in both diseases. We conducted a case-control association study in a sample of 439 non-diabetic patients with late-onset AD and 304 cognitively healthy, non-diabetic elderly controls to determine the potential risk for developing AD associated with SLC2A1 rs841847 polymorphism. The rs841847 C/C genotype occurrence was higher in the AD group (AD: 60.4%, controls: 50.7%), while the minor T allele-containing genotypes were more frequent among controls (AD: 39.6%, controls: 49.3%). A multivariate logistic regression model adjusted for age, sex, and apolipoprotein E (APOE) ε4 status (ε4 allele carriers versus non-carriers) demonstrated that carriers of the T allele had a significantly reduced risk for AD compared to C/C homozygotes (OR = 0.672; 95% CI: 0.493–0.916; p = 0.012). Although the rs841847 polymorphism has been linked to type-2 diabetes mellitus, the present study investigated this gene variant in AD for the first time. Our findings indicate a moderate protective effect for the rs841847 T allele on the susceptibility to AD. We demonstrated the rs841847 polymorphism as a candidate single nucleotide polymorphism for further examination as a predisposing genetic factor for AD. Full article

Background: Grain length is a key determinant of yield and quality in barley (Hordeum vulgare L.) and is typically governed by complex quantitative traits. Methods: In this study, a diverse natural population comprising 198 barley accessions was evaluated across two years to investigate the genetic basis of grain length. Results: Phenotypic analysis revealed continuous variation with near-normal distribution, indicating polygenic control. Genome-wide association study (GWAS) identified 84 stable single nucleotide polymorphism (SNP) loci significantly associated with grain length, predominantly enriched on chromosome 7. RNA sequencing (RNA-seq) was conducted using two contrasting genotypes at four developmental stages. Differentially expressed genes (DEGs) were mainly enriched in structural constituent of chromatin, protein heterodimerization activity, and the starch and sucrose metabolism. Integration of GWAS and RNA-seq identified 7 key candidate genes seven key candidate genes, including LOC123412467, LOC123408579, LOC123407599, LOC123410619, LOC123410954, LOC123411868, and LOC123426274. Sequence variation analysis further revealed functional polymorphisms, including non-synonymous mutations. The sequencing results show that LOC123412467 and LOC123410619 exhibited consistent allelic variation between long-grain and short-grain accessions, while LOC123426274 displayed stable differential expression across developmental stages, indicating their potential roles as key genes controlling grain length. Conclusions: Collectively, these findings suggest that chromosome 7 contains major regulatory loci controlling barley grain length and demonstrate that integrative multi-omics analysis is an effective strategy for identifying high-confidence candidate genes associated with complex agronomic traits. This study provides valuable insights into the genetic basis of grain length and offers key candidate genes for barley molecular breeding. Full article

C-reactive protein (CRP) was discovered as a protein that reacts with C-polysaccharides to form precipitates in the serum of patients with pneumococcal infection. Subsequently, it was found to increase in the serum of patients with bacterial infections and rheumatic diseases, and it has since been widely recognized as a nonspecific biomarker of acute inflammation and utilized in clinical medicine. Meanwhile, CRP-like proteins are also present in the hemolymph of horseshoe crabs, and it has become clear that these proteins have long played a crucial role in the humoral innate immune response against foreign microorganisms. In recent years, advances in molecular analysis have revealed the details of the complex biological functions performed by CRP. Furthermore, with the development of highly sensitive CRP measurement methods, its importance as a biomarker is gaining attention not only in acute inflammatory diseases but also in chronic inflammatory diseases such as cardiovascular disease, diabetes, cancer and neurological disorders. New treatment strategies targeting CRP, based on recent findings, are also being explored. Full article

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease of the pulmonary vasculature characterized by obliterative remodeling of small pulmonary arteries, leading to sustained elevation of pulmonary vascular resistance, right ventricular failure, and premature death. The diagnostic gold standard remains right heart catheterization, requiring a mean pulmonary artery pressure greater than 20 mmHg at rest, a pulmonary arterial wedge pressure of 15 mmHg or below, and a pulmonary vascular resistance exceeding 2 Wood units. PAH is an autosomal dominant disorder with markedly incomplete penetrance of approximately 20–30%, indicating that germline mutations alone are insufficient to cause disease. Disease manifestation requires additional “second hits”, including chronic hypoxia, systemic inflammation, hemodynamic stress, hormonal influences, and common genetic modifiers such as single-nucleotide polymorphisms (SNPs). This genetic and environmental complexity underpins the broad clinical heterogeneity observed across PAH subtypes, which include idiopathic PAH, heritable PAH, and disease associated with connective tissue disorders, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and drug or toxin exposure. This review provides a comprehensive and critical appraisal of the molecular-genetic architecture of PAH. Thirty genes have now been implicated in disease pathogenesis, spanning seven functional categories: receptors of the TGF-β/BMP signaling family (BMPR2, ACVRL1, ENG, BMPR1B); circulating BMP ligands (GDF2, BMP10); transcription factors (TBX4, SOX17, KLF4, FOXF1, SMAD1, SMAD4, SMAD9); membrane and polyamine transporters (ATP13A3, AQP1); potassium channel regulators (KCNA5, KCNK3, ABCC8); metabolic and mitochondrial genes (EIF2AK4, NFU1, GGCX); signaling receptors and structural proteins (NOTCH3, KDR, CAV1, PLEKHH2); vasoactive and extracellular matrix regulators (KLK1, CBLN2, CD248); and epigenetic regulators (TET2, TOPBP1). Among these, BMPR2 is the dominant contributor, accounting for 53–86% of heritable PAH and 14–35% of idiopathic cases. The remaining genes each account for fewer than 5% of cases individually, collectively reflecting a broad landscape of rare and ultra-rare genetic contributions. For each gene, we critically evaluate the strength of genetic evidence, pathogenic mechanisms, degree of mechanistic resolution, and clinical relevance. We further discuss the contribution of emerging technologies, including whole-genome sequencing, single-cell and spatial transcriptomics, multi-omics integration, iPSC-derived vascular models, and artificial intelligence, to expanding the PAH genetic architecture beyond single-gene discovery. A key theme across this landscape is convergence: despite mechanistic diversity at the gene level, most PAH-associated variants ultimately impair endothelial quiescence, promote smooth muscle proliferation, and drive apoptosis resistance through disruption of BMP signaling amplitude, transcriptional stability, ion channel homeostasis, metabolic integrity, or epigenetic regulation. This convergence supports both a unified therapeutic rationale and a precision medicine framework for genotype-stratified intervention in PAH. Full article

Background/Objectives: Cardiovascular diseases remain a leading cause of global mortality. The C-X-C motif chemokine ligand 12 (CXCL12) gene has been implicated in atherosclerosis; however, its relationship with lipoprotein subfraction profiles remains unclear. The primary objective of this study was to investigate the association between the CXCL12 rs1801157 C>T single nucleotide polymorphism (SNP) and coronary artery disease (CAD) risk in a Turkish population. The secondary objective was to evaluate the relationship between this polymorphism and LDL and HDL lipoprotein subfraction profiles. Methods: This case–control study included 139 patients with angiographically confirmed CAD and 125 healthy controls. Genotyping was performed using TaqMan real-time polymerase chain reaction (PCR). Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were analyzed using the Lipoprint^® polyacrylamide gel electrophoresis system. Multivariable logistic and linear regression analyses were performed, adjusting for age, sex, body mass index (BMI), and major cardiovascular risk factors. Results: No significant differences in rs1801157 genotype or allele distributions were observed between groups (overall χ² = 0.459, p = 0.796). Logistic regression confirmed that the polymorphism was not an independent predictor of CAD risk (CT: OR = 1.396, p = 0.409; TT: OR = 1.458, p = 0.694). HDL-C was an independent protective factor (OR = 0.952, 95% CI: 0.910–0.996; p = 0.029). Notably, TT homozygous carriers exhibited significantly higher large HDL (p = 0.018) and intermediate HDL (p < 0.001) subfraction levels and markedly lower small LDL concentrations (p < 0.001). Multivariable linear regression confirmed these associations were independent of age, sex, and BMI. Conclusions: The CXCL12 rs1801157 variant does not directly influence CAD susceptibility but modulates lipoprotein quality by promoting larger HDL subfractions and reducing atherogenic small LDL particles, suggesting an indirect cardioprotective role through lipid metabolism. Full article