AA Genotype Research Articles

Polymorphisms Influence the Expression of the Fas and FasL Genes in COVID-19

The apoptotic molecule Fas and its ligand FasL are involved in the process of T-lymphocyte death, which may lead to lymphopenia, a characteristic of severe coronavirus disease 2019 (COVID-19). In this study, we investigated the influence of polymorphisms in the FAS and FASL genes, FAS and FASL gene expression, and plasma cytokine levels on COVID-19 severity and long COVID occurrence. A total of 116 individuals with severe COVID-19 and 254 with the non-severe form of the disease were evaluated. In the post-COVID-19 period, samples from 196 individuals with long COVID and 67 from people who did not have long COVID were included. Genotyping and quantification of gene expression were performed via real-time PCR, and cytokine measurement was performed via flow cytometry. The AA genotype for FAS rs1800682 (A/G) and the TT genotype for FASL rs763110 (C/T) were associated with increased FAS and FASL gene expression, respectively (p < 0.005). Higher plasma IFN-γ levels were associated with higher FAS and FASL gene expression (p < 0.05). Among individuals with non-severe COVID-19, carriers of the AA genotype for FAS rs1800682 (A/G) had higher levels of FAS expression, more symptoms, and higher IFN-γ levels (p < 0.05). No association of the evaluated markers with long COVID were observed. The AA genotype of FAS rs1800682 (A/G) and the TT genotype of FASL rs763110 (C/T) influence the levels of FAS and FASL gene expression. Higher gene expression of FAS and FASL may lead to greater inflammation in COVID-19 patients, with higher levels of IFN-γ and T lymphocyte death.

Effects of SCT genetic polymorphisms on methotrexate concentrations and toxicities in Chinese children with acute lymphoblastic leukemia

Solute carrier (SLC) transporters play a crucial role in facilitating the cellular uptake of various anticancer drugs, such as methotrexate (MTX). This study aimed to analyze the impact of nonsynonymous single nucleotide polymorphisms (SNPs) in SLC19A1, SLCO1B1, and SLCO1B3 on MTX exposure, toxicities, and prognosis in 148 patients with acute lymphoblastic leukemia (ALL). The SLCO1B3 rs7311358 polymorphism was significantly associated with the median dose-normalized MTX concentrations at 24 h (p < .05). There were significant differences in the proportions of patients with serum MTX levels >40 µmol/L at 24 h among SLC19A1 rs1051266 GG, GA, and AA genotype carriers (29.0, 24.7, and 6.2%, respectively, p < .05). The SLC19A1 rs1051266 G > A polymorphism also displayed significant associations with hematological (p < .05) and hepatic toxicities (p < .01). Our findings indicate that the analysis of SNPs in solute carrier transporters (SCTs) could offer valuable insights into the interpatient variability of MTX pharmacokinetics and toxicities in ALL children.

Association analysis of genetic polymorphisms of METTL3 with clinical outcomes in a Chinese pediatric population with primary brain tumors.

Methyltransferase-like 3 (METTL3) regulates numerous biological processes and diverse cancers. To explore the frequency distribution of METTL3 rs1061026, rs1139130, and rs1263801 polymorphisms, and their potential impacts on clinical outcomes and chemotherapy-induced toxicities in a cohort of Chinese pediatric patients diagnosed with primary brain tumors (PBTs). Genotyping for three investigated SNPs was performed in 107 pediatric patients with PBTs using the Sequenom MassARRAY iPLEX platform. Serum METTL3 levels were determined by Enzyme-Linked Immunosorbent Assay. Serum methotrexate (MTX) concentrations were quantified utilizing fluorescence polarization immunoassay. The three investigated SNPs were not significantly associated with the risks of relapse and metastasis after adjusting all confounders. Compared to individuals with the rs1139130 GG genotype, GA genotype carriers exhibited a significantly higher risk of oral mucositis (adjusted OR: 7.504; 95 % CI, 1.931-29.436; P = 0.004). The rs1139130 GA (adjusted OR: 5.091; 95 % CI, 1.351-19.176; P = 0.016) and AA (adjusted OR: 9.588; 95 % CI, 1.769-51.949; P = 0.009) genotype carriers exhibited a significantly lower risk of fever than GG genotype carriers. The median dose-normalized MTX concentrations at 42 h were lower with borderline significance in children with rs1061026 GT and GG genotypes (0.004 μmol/L per g/m2) than the TT genotype carriers (0.006 μmol/L per g/m2, P = 0.048). Patients with the rs1139130 GA genotype had significantly higher median serum METTL3 protein levels (59.91 ng/mL) than GG genotype carriers (44.57 ng/mL, P = 0.015). This study demonstrated the association of the rs1139130 polymorphism with the development of oral mucositis and fever and the rs1061026 polymorphism with MTX exposure.

Association of NOS2A Gene Polymorphisms with Susceptibility to Tuberculosis in Manipuri Population of Northeast India.

Single nucleotide polymorphisms (SNPs) have been reported to influence the activity of specific genes involved with the innate immune response to Mycobacterium; hence, they are crucial in tuberculosis (TB) susceptibility studies. The study aimed to investigate the polymorphism in the NOS2A (Nitric oxide synthase 2A)geneand its association with susceptibility to TB in the Manipuri population of northeast India. This case-control study includes 495 subjects- 220TB patients and 275 control individuals. TaqMan allelic discrimination assay was used to study the gene polymorphism, and Griess's test was employed to determine the serum nitric oxide (NO) levels. Serum NO levels were analysed to correlate with the functional changes associated with the polymorphisms. Two SNPs of the gene,NOS2A(rs8078340 and rs2274894), were studied. For the SNP-rs8078340, a significant difference in the genotypic and allelic frequencies was observed between the cases and control groups (p = 0.001; AA genotype OR = 30.288, 95% CI: 1.703-538.44 and A allele OR = 2.937, 95%CI: 1.762-4.896). However, for the SNP-rs2274894, only the T allele (with OR = 1.464; 95%CI: 1.080-1.983, p = 0.014) was associated with susceptibility to TB. Serum levels of NO were significantly different between the cases and control groups (p < 0.05). Significant associations of both homozygous AA genotype and allele A of the NOS2A (rs8078340) and minor allele T of NOS2A (rs2274894) were observed with susceptibility to TB. Patients with the AA genotype of NOS2A show a higher NO level, suggesting its role in greater expression of the NOS2A gene.

Exploring associations between the FTO rs9939609 genotype and plasma concentrations of appetite-related hormones in adults with obesity.

Associations between variants in the FTO locus and plasma concentrations of appetite related hormones are inconsistent, and might not work in a dose dependent fashion in people with obesity. Moreover, it is relevant to report meal related plasma concentrations of these hormones in persons with obesity given the growing interest in their pharmacological potential in obesity therapy. We find it clinically relevant to examine associations between the SNP rs9939609 genotypes and homeostatic appetite regulation in individuals with BMI ≥35 kg/m2. This study explored associations of the rs9939609 genotypes to plasma concentrations of acylated ghrelin, active glucagon-like peptide 1 (GLP-1), and total peptide YY (PYY), and moderating effects of fat mass (FM), in 96 adults (69% female) with BMI ≥35 kg/m2, using a cross sectional observation study designed to have 1/3 of participants each with genotypes TT, AT and AA, respectively. Participants were median (25th, 75th percentile) 42.5 (32, 50) years of age, weighed 120.9 (109.6, 142.4) kg, and had a BMI of 42.8 (39.5, 46.4) kg/m2. Acylated ghrelin, active GLP-1, and total PYY were measured in the fasted state and half-hourly for 2.5h after a standardized meal. We evaluated associations between genotype and appetite hormones in regression analysis controlling for FM and sex. Genotype did not associate with fasting or postprandial (area under curve, AUC) GLP-1 or PYY. Genotype did not associate with fasting acylated ghrelin, but in females with genotype AA, increased FM was associated with higher fasting and postprandial (AUC) acylated ghrelin concentrations relative to genotypes TT (fasting p = 0.025; AUC p = 0.004) and AT (fasting p = 0.002; AUC p < 0.001). This novel finding warrants further investigation.

The role of vitamin d receptor gene polymorphisms in obesity: a systematic review and meta-analysis

Introduction: Obesity has become a major global issue since it can increase the risk of fatal disease. Genetic variation in the vitamin D receptor (VDR) gene is a potential candidate for obesity, though findings are inconclusive. Objectives: This meta-analysis aims to determine the association between VDR polymorphisms and obesity risk.Methods: All relevant studies from 1990 to January 2024 were screened using PubMed, Web of Science, Science Direct, and Scopus. This meta-analysis included studies meeting PROSPERO-registered eligibility criteria. Pooled odds ratios (OR) with 95% confidence intervals (CI) for six VDR gene polymorphisms (BsmI, FokI, TaqI, ApaI, and Cdx2) were generated using RevMan 5.4.Results: This meta-analysis included 23 studies with 5715 obese/overweight and 4887 non-obese individuals from China, Malaysia, Egypt, Turkey, India, Iran, UAE, Saudi Arabia, Czech Republic, Greece, USA, Denmark, Hungary, and Belgium. The findings show an association between VDR ApaI polymorphism and reduced obesity risk in homozygous models [aa vs. AA: OR=0.76, CI=0.60-0.97; P=0.03]. The TaqI variant is linked to increased obesity risk in Europeans under allelic [t vs. T: OR=1.33, CI=1.11-1.60; P=0.002], homozygous [tt vs. TT: OR=1.68, CI=1.13-2.50; P=0.010], dominant [tt vs. TT+Tt: OR=1.47, CI=1.07-2.03; P=0.02], and recessive [Tt+tt vs. TT: OR=1.43, CI=1.08-1.89; P=0.01] models.Conclusions: This meta-analysis suggests the aa genotype of VDR ApaI polymorphism may protect against obesity across populations. In Europeans, the t allele of VDR TaqI polymorphism is identified as an obesity risk factor

Relationship of Serum 25-Hydroxyvitamin D Concentrations, Diabetes, Vitamin D Receptor Gene Polymorphisms and Incident Venous Thromboembolism.

The association between vitamin D and the risk of venous thromboembolism (VTE) remains inconclusive. We aimed to explore the association of serum 25-hydroxyvitamin D (25OHD) with incident VTE among participants with and without diabetes, and examine the modifying effect of genetic susceptibility of VTE and vitamin D receptor (VDR) gene polymorphisms on this association. A total of 378,082 participants free of VTE at baseline from the UK Biobank were included. Serum 25OHD concentrations were measured by the chemiluminescent immunoassay method. The primary outcome was incident VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). The genetic risks of VTE were estimated using 297 single nucleotide polymorphisms (SNPs) associated with VTE. The VDR gene polymorphisms included SNPs of rs7975232, rs1544410, rs2228570 and rs731236. During a median follow-up duration of 12.5years, 10,645 VTE cases were recorded. Serum 25OHD had a significantly stronger inverse association with incident VTE in participants with diabetes (per SD increment, adjusted HR: 0.87; 95% CI: 0.81-0.93) than in those without diabetes (per SD increment, adjusted HR: 0.97; 95% CI: 0.95-0.99; p-interaction=0.003). Similar trends were found for incident DVT and PE. Among participants with diabetes, the genetic risk of VTE did not significantly modify the association between serum 25OHD and incident VTE (p-interaction=0.607). However, a stronger inverse association of serum 25OHD with incident VTE was found in the VDR rs2228570 AA genotype (vs. GG/AG; p-interaction=0.031). Serum 25OHD was inversely associated with the risk of VTE, especially among participants with diabetes, regardless of genetic risks of VTE.

The Clinical utility of Interleukin-17A rs2275913 polymorphism with colorectal cancer in Egyptian patients

year throughout the world, according to the World Health Organization 2022. CRC is the third most prevalent disease and the second most common cancer in terms of fatality. People diagnosed with colorectal cancer in the early stages have a five-year survival rate of roughly 95%, but people identified with the disease in the later stages have a survival rate of approximately 12%. There are a number of variables that contribute to the development of CRC, these factors include both hereditary and environmental influences. We aimed to investigate the clinical utility of Interleukin (IL)-17A rs2275913 polymorphism to assess its association with CRC in Egyptian patients and the ability of using it as a non-invasive biomarker to assist in diagnosis of colorectal cancer. This case–control study included 75 subjects. Of these, 35 were CRC cases, 20 inflammatory bowel disease (IBD) patients and 20 normal control persons. Blood was collected and DNA extracted. The rs2275913 of IL-17A was genotyped using the Real-Time polymerase chain reaction (PCR). In CRC patient’s group, (5.71%) had the homozygous AA genotype, (40%) the heterozygous GA genotype and (54.29%) the wild GG genotype. While in IBD group (15%) had the homozygous AA genotype, (40%) the heterozygous GA genotype and (45%) the wild GG genotype. In the normal control group, no one had the homozygous AA genotype, but (45%) had the heterozygous GA genotype and (55%) the wild type of GG genotype. However, there was no statistically significant substantial variation amongst the three groups (p&gt;0.05). In conclusion, our study demonstrated no association of IL-17A rs2275913 with both CRC and IBD in the Egyptian population.

Association between BCL2 interacting protein 3 like (BNIP3L) genetic polymorphisms and the risk of multiple myeloma in China

ABSTRACT Background: The BCL2 interacting protein 3-like (BNIP3L) protein is involved in multiple myeloma (MM) development and progression. This study aims to explore the connection between BNIP3L single-nucleotide polymorphisms (SNPs) and MM. Methods: SNaPshot was used to examine six SNP loci of the BNIP3L gene in enrolled subjects. The relationship between these loci and MM susceptibility and prognosis was explored. Survival analysis was used to evaluate the impact of different factors on patient survival. Results: The rs2874670 AA genotype and A allele were associated with increased MM risk (P < 0.05). The CCACAC haplotype had a higher frequency in MM, while CCGCAC had a higher frequency in normal patients (all P < 0.05). Patients with R-ISS stage I and II had higher survival rates than those with stage III (P < 0.05). Patients, who received chemotherapy followed by autologous stem cell transplantation, had longer survival time than those who only received chemotherapy (P < 0.05). Low levels of LDH and β2-MG were associated with better survival rates (P < 0.05). Cox regression identified that LDH levels, β2-MG levels, and R-ISS staging were the risk factors for the death of MM. Mann-Whitney U test found a significant difference in survival time between MM patients with different BNIP3L rs2874670 genotypes after BD chemotherapy (P < 0.05). Conclusion: To our knowledge, this is the first study to find that BNIP3L rs2874670 could increase MM susceptibility in China. Different BNIP3L rs2874670 genotypes may affect the prognosis of MM patients receiving BD chemotherapy.

A study of polymorphism and the serum level of Haptoglobin of people suffering from sickle cell disease and/or hepatitis C

Background. Haptoglobin is a type of alpha2 globulin found in human plasma. Its primary function is to bind to the globin portion of free hemoglobin in the bloodstream. Objectives. To examine the genetic polymorphism of the Haptoglobin (Hp) gene in patients diagnosed with sickle cell anemia, hepatitis C, and the co-occurrence of sickle cell anemia and hepatitis C . Patients and methods. A total of 130 participants were categorized into several groups: 40 patients with sickle cell anemia, 40 patients with hepatitis C, 10 patients with both sickle cell anemia and hepatitis C, and 40 individuals in the control group. The DNA was extracted and the polymerase chain reaction (PCR) was conducted using genotype-specific primers for the three areas of the haptoglobin gene. The genotypes were identified by running electrophoresis on agarose gels and calculating the proportion of each allele that was amplified. After obtaining the sequencing results of the haptoglobin gene and for the studied samples and for the three plots Hp2, Hp 1S and Hp 1F, Sequences for all three segments were registered in the NCBI Genome Bank for the first time locally and some were given independent accession numbers, and it will be considered a database for any future researcher working on the Hp genotypes in Iraq. Results. In Sickle cell Patient Hp1-1(0.13), Hp2-2(0.55), Hp2-1(0.32), Hepatitis-C Patient Hp1-1(0.13), Hp2-2(0.63), Hp2-1(0.24), Sickle cell with Hepatitis C Patient Hp1-1(0.20), Hp2-2(0.60), Hp2-1(0.20), and Control group Hp1-1 (0.30), Hp2-2 (0.50), Hp2-1 (0.20). Hp2-2 was the most common phenotype across all categories, The T allele and TT genotype seem more visible in sickle cell anemia and hepatitis diseases than the AA genotypes of Hp-2 643 T&gt;, and no correlation between patients and health control group with Hp1S gene. Also, the present study reports that there is no correlation between patients of sickle cell anemia and health control group with Hp-1F 867 G &gt; A gene, but the G allele and GG genotype more visible in hepatitis diseases than the AA genotypes of Hp-1F 867 G &gt; A gene. Conclusions. The Hp2-2 haptoglobin phenotype was the most common among patients. Different groups may have an influence on the development of sickle cell anemia and hepatitis C.

Genotype frequency analysis of rs2025804 LEPR genetic variant in Iranian population.

The LEPR gene is a key focus in obesity research, with studies linking its polymorphisms to various diseases like polycystic ovarian syndrome and energy intake disorders. This study aims to investigate the prevalence of the rs2025804 variant within LEPR and its distribution among healthy individuals across diverse ethnic groups in Iran. The frequency of the rs2025804 genotype in the LEPR gene was analyzed in 1142 healthy adults representing different ethnicities in Iran. Saliva samples were randomly collected, and genomic DNA was extracted using a standard kit. Genotyping was performed using the Illumina Infinium Global Screening Array-24 BeadChip. Genotype and allele frequencies were calculated using SPSS software version 22, with a 95% confidence level. Among the 1142 individuals surveyed across 29 provinces, 683 (59.81%) had genotype AA, 408 (35.73%) had genotype AG, and 51 (4.47%) had genotype GG. The allele frequencies for A and G were found to be 1774 (77.67%) and 510 (22.32%), respectively. Our findings show a unique allele distribution compared to other ethnic groups, with genotype AA being the most prevalent (59.81%), followed by AG (35.73%) and GG (4.47%). Allele frequencies are A (77.67%) and G (22.32%). This study documents the genotype and allele frequencies of rs2025804 in the LEPR gene among healthy Iranians for the first time. Routine LEPR genotyping could potentially serve as a screening tool for obesity-related disorders, given these results. This enhances our understanding of genetic diversity and holds promise for targeted healthcare interventions.

Four SNPs in the untranslated region of the NOTCH2 gene involved in reproductive traits in fertile and anestrum Holstein Friesian cattle

BackgroundThere are no studies belong NOTCH2 gene polymorphism in relation to reproductive and productive traits in Holstein cattle. The objective of the present study was to investigate the effect of NOTCH2 gene polymorphisms on productive and reproductive performance of fertile and anestrum cattle.MethodsThe cattle were classified into anestrus for 3–12 months postpartum (n = 115, 37.7%) and normal cyclic fertile (n = 190, 62.3%). Age at 1st calving, calving interval, calf birth weight, milk yield and days of milking data were obtained from the farm records for all animals. Blood samples were collected from fertile and anestrum animals for DNA extraction and the PCR as well as single-strand conformation polymorphism techniques (SSCP) were performed for detection of the NOTCH2 gene polymorphism.ResultsThe sequencing results showed that NOTCH2 gene in cattle is polymorphic with 5 genotypes AA, AG, GG, CC and CT. Four novel SNPs as transition single base substitution mutations were detected at 3: 23,192,033 (A/G), 3:23192149 (C/T), 3:23192071 (C/T) and 3:23192143 (G/A). GG genotype of NOTCH2 gene was associated with shorter calving interval and heavier calf birth weight in both fertile and anestrum cattle.ConclusionsNOTCH2 gene in cattle could be used as a genetic marker involved in reproductive traits in both fertile and anestrum cattle.

A Preliminary Screening of Single Nucleotide Polymorphism (SNP) of A1 and A2 Beta-casein Alleles in Dairy Cattle

Milk containing A1 variants in the beta-casein gene is considered to be a risk factor for coronary heart disease (CHD), type I diabetes (DM-I), autism, and schizophrenia due to the release of beta-casomorphin 7 (BCM-7). The objectives of this study were to screen for polymorphism of beta-casein in dairy cattle and to examine the allelic and genotypic frequencies of A1 and A2 variants. A total of 290 cattle blood samples were collected from two states and the samples were extracted. This was followed by PCR amplification for exon 7 of the beta-casein gene (CSN2). The PCR products were then subjected to DNA sequencing. The sequencing results were aligned and the variants were screened. In Pahang, 125 samples are of the A2A2 genotype, followed by A1A2 (n=97) and A1A1 (n=28). While in Melaka, the highest genotype was A2A2 (n=20) as compared to A1A2 (n=18) and A1A1 (n=2). Meanwhile, the frequency of the A2 allele was higher than A1 in both states. The high genotypic frequencies of A2A2 in these cattle populations could be influenced by the cattle breed as well as the rate of crossbreeding on the farm. Thus, screening of dairy cattle for A1 and A2 beta-casein could be used in selecting the preferred animals for breeding.

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

Maximal Fat Oxidation During Exercise in Healthy Individuals: Lack of Genetic Association with the FTO rs9939609 Polymorphism

Background/Objectives: Previous studies suggest that there is a genetically determined component of fat oxidation at rest and during exercise. To date, the FTO gene has been proposed as a candidate gene to affect fat oxidation during exercise because of the association of the “at-risk” A allele with different obesity-related factors such as increased body fat, higher appetite and elevated insulin and triglyceride levels. The A allele of the FTO gene may also be linked to obesity through a reduced capacity for fat oxidation during exercise, a topic that remains largely underexplored in the current literature. The aim of this study was to analyze the association between the FTO rs9939609 polymorphism with the rate of fat oxidation during exercise and metabolic syndrome criteria in healthy participants. Methods: A total of 80 healthy participants (41 men and 39 women) underwent comprehensive assessments, including measurements of anthropometric variables, blood pressure and blood measures of fasting glucose, triglycerides, low- and high-density lipoprotein cholesterol (LDL-c and HDL-c), insulin, interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations. Additionally, the Homeostatic Model Assessment (HOMA-IR) was used to evaluate insulin resistance. Peak oxygen uptake (VO2peak) and maximal fat oxidation rate (MFO) were also measured during an incremental cycling test. FTO rs9939609 genotyping (TT, AT, AA) was performed using genomic DNA samples obtained from a buccal swab and measured with PCR. Results: There were 32 participants (40.0%) with the TT genotype; 31 (38.8%) with the AT genotype; and 17 (21.2%) with the AA genotype. Age, body characteristics, VO2peak, blood pressure and blood variables were similar across all three genotypes. However, serum insulin concentration and HOMA-IR were associated with the FTO rs9939609 genotype with higher values in AA with respect to AT and TT participants (p &lt; 0.050). Still, MFO was similar in TT, AT and AA participants (0.35 ± 0.13, 0.37 ± 0.11, 0.33 ± 0.11 g/min, p = 0.702). In the dominant model, there was no statistical difference between TT and A allele carriers. However, the recessive model revealed that AA participants had higher values of body mass, body mass index, blood insulin concentration and HOMA-IR than T allele carriers (p &lt; 0.050), with no differences in MFO. Conclusions: In our sample of healthy individuals, the FTO rs9939609 polymorphism was associated with several phenotypes associated with obesity and insulin resistance, particularly under the AA vs. T allele/recessive model. However, the FTO rs9939609 polymorphism was not associated with MFO during exercise as fat oxidation was similar across genotypes. This suggests that reduced fat oxidation during exercise is unlikely to be a cause of the obesogenic influence of the FTO AA genotype. Clinically, these findings suggest that the obesogenic effects of the FTO AA genotype are unlikely driven by impaired fat oxidation during exercise. Instead, attention should focus on mechanisms like appetite regulation and energy intake. Moreover, exercise interventions may still effectively mitigate obesity risk, as AA individuals retain normal fat oxidation capacity during exercise.

Interferon Gamma Gene Polymorphisms in Greek Primary Breast Cancer Patients.

Breast cancer is a heterogeneous disease with distinct clinical subtypes, categorized by hormone receptor status, which exhibits different prognoses and requires personalized treatment approaches. These subtypes included luminal A and luminal B, which have different prognoses. Breast cancer development and progression involve many factors, including interferon-gamma (IFNG). Moreover, single nucleotide polymorphisms (SNPs) in IFNG have been associated with cancer risk. However, the functional role of IFNG polymorphisms in primary breast cancer subtypes, luminal A and luminal B, is unclear. A total of 138 breast cancer tissues were acquired: 81 had luminal A, 42 had luminal B, 10 had triple-negative, and 3 had human epidermal growth factor receptor 2 (HER2) subtypes, while 2 had missing data. The tissues were evaluated in relation to luminal A and luminal B primary breast cancer subtypes. DNA was extracted from freshly frozen samples, and three SNPs (rs1861493 (chr12:68157416 (GRCh38.p13)), rs1861494 (chr12:68157629 (GRCh38.p13)) and rs2430561 (chr12:68158742 (GRCh38.p13))) in the IFNG gene were selected and evaluated based on previously published associations with cancer or other diseases. The data showed that IFNG polymorphisms rs1861493 and rs1861494 were associated with breast cancer risk, with the A allele of rs1861493 and T allele of rs1861494 being noted as the risk alleles. Furthermore, the IFNG polymorphism rs2430561 was associated with breast cancer risk, with the A allele being the risk allele. In addition, the risk alleles were more prevalent in the more aggressive subtype, luminal B breast cancer, compared to luminal A. Similarly, the rs2430561 AA genotype was associated with the breast cancer severity. IFNG polymorphisms rs1861493, rs1861494, and rs2430561, with their respective risk alleles, are associated with increased breast cancer risk and severity. These risk alleles are more prevalent in the aggressive luminal B subtype compared to luminal A, indicating their role in both the prevalence and prognosis of breast cancer in a Greek population.

The role of SNP (rs11908352) genetic polymorphisms on serum level of matrix metalloproteinase-9 in rheumatoid arthritis

Background. MMP-9 plays a significant role in the destruction of the extracellular matrix (ECM) in various physiological and pathological processes, including tissue remodeling. MMP-9 is elevated in pathologies involving abnormal immune responses. The extent of joint damage varies significantly among individuals with rheumatoid arthritis (RA), and much of its genetic inheritance remains unexplained. Multiple autoimmune diseases share common genetic risk factors that may also influence disease progression. Genetic variants in MMP-9 could potentially affect its transcriptional expression or enzymatic activity. Objective. To evaluate the impact of serum MMP-9 levels and the SNP (rs11908352) in a group of patients with rheumatoid arthritis compared to a control group. Methods. Seventy-three RA patients with a mean age of 47.91 ± 1.44 years were included in this study, compared to sixty-eight healthy controls matched in age and gender, with a mean age of 46.42 ± 1.51 years. Serum levels of MMP-9 and rs11908352 SNPs were examined in individuals with RA and compared to the control group. Results. The findings revealed a notable increase in MMP-9 levels in RA patients compared to healthy controls (1.85 ± 0.12 vs. 1.31 ± 0.10). Additionally, rs11908352 SNP analysis showed a statistically insignificant rise in the frequency of the AA genotype and A allele in the patient group compared to controls (24.66% vs. 16.18%; p = 0.297; OR = 1.70) and (51.0% vs. 44.0%; p = 0.285; OR = 1.30), respectively. Genotype frequencies CA, CC, and allele frequency C showed nonsignificant decreases in RA patients compared to controls (52.05% vs. 55.88%; p = 0.736; OR = 0.86), (23.29% vs. 27.94%; p = 0.566; OR = 0.78), and (49.0% vs. 56.0%; p = 0.285; OR = 0.77), respectively. Patients with the AA genotype exhibited markedly elevated serum MMP-9 levels compared to the control group (p = 0.007). Conclusion. The results of this study demonstrated a significant correlation between serum MMP-9 levels and rs11908352 genetic variation in RA patients, suggesting that specific genetic regions associated with autoimmune diseases may influence the severity of joint damage in rheumatoid arthritis.

Impact of Thrombomodulin Polymorphism -33G>A on Acute Myocardial Infarction Risk and Circulating Inflammatory Markers.

There is increasing evidence that thrombomodulin (THBD) polymorphisms, along with inflammatory markers [i.e., C-reactive protein (CRP), fibrinogen, albumin], may increase the risk of acute myocardial infarction (AMI). The aim of the study was to investigate the role of the THBD -33G>A polymorphism (rs1042579) as a marker of AMI risk and to correlate it with serum levels of inflammatory markers. Case-control study of 277 AMI patients and 329 healthy controls. A binary logistic regression analysis was performed to evaluate the association between the parameters studied and AMI risk. The frequencies of genotypes AA, GA, and GG of the THBD -33G>A polymorphism were 31.4%, 45.5%, and 23.1% in patients and 21.6%, 44.1%, and 34.3% in controls. A significant association was found between the AA genotype of the THBD -33G>A polymorphism (AA: OR = 2.011, 95% CI 1.561-3.074, P < .001) or A allele (A: OR = 1.725, 95% CI 1.493-2.510, P < .001) and AMI risk. A backward stepwise logistic regression method combining AMI status as the dependent variable and conventional risk factors (age, smoking, arterial hypertension (HTA), diabetes, dyslipidemia, CRP, albumin, fibrinogen, serum angiotensin converting enzyme (ACE) activity, serum malondialdehyde, conjugated dienes, glutathione peroxidase, cardiac troponin-I (cTnI) and THBD AA genotype) as independent variables showed that the most predictive risk factors for AMI were smoking, HTA, albumin, fibrinogen, CRP, ACE activity, cTnI, and the THBD AA-genotype with odds ratios of 2.942, 2.203, 2.352, 1.323, 1.652, 1.014, 2.105, and 3.781 respectively. The AA genotype was associated with increased diastolic blood pressure, CRP, ACE activity, and albumin levels. The study shows that the THBD -33G>A polymorphism should be included in the stratification of AMI risk.

Association Among MCT1 rs1049434 Polymorphism, Athlete Status, and Physiological Parameters in Japanese Long-Distance Runners.

Monocarboxylate transporters (MCTs) comprise 14 known isoforms, with MCT1 being particularly important for lactate transport. Variations in lactate metabolism capacity and aerobic performance are associated with the T1470A polymorphism in MCT1. We aimed to investigate the frequency of the T1470A polymorphism and compare relevant physiological parameters among long-distance runners, wherein these parameters are fundamental to athletic performance. We included 158 Japanese long-distance runners (LD) and 649 individuals from the general Japanese population (CON). The frequency of the T1470A polymorphism was compared between these groups and across athletic levels using the chi-square test. Additionally, physiological data were collected from 57 long-distance runners, and respiratory gas measurements were obtained using the mixing-chamber method during a graded incremental exercise test. We observed a significant difference between the LD and CON groups in the dominant model and between the sub-28 min group and 28 min or above group in the recessive model. As the competitive level increased, the frequency of the AA genotype also increased. When comparing physiological parameters between the AA genotype and T allele, subjects with the AA genotype showed significantly higher values for oxygen uptake at lactate threshold (p = 0.001), oxygen uptake at onset of blood lactate accumulation (p = 0.01), maximal oxygen uptake (p = 0.005), and maximal blood lactate concentration (p = 0.038). These results suggest that the AA genotype of the T1470A polymorphism of MCT1 is an effective genotype associated with athletic status and aerobic capacity in Japanese long-distance runners.

Vitamin D binding protein and receptor prevalence in a large population with periodontitis: single nucleotide polymorphism and transcriptomic profiling

BackgroundThere is an ongoing controversy regarding the expression of vitamin D receptor (VDR) and binding protein (VDBP) genes, as well as their polymorphisms, in periodontitis. We examined eight single nucleotide polymorphisms (SNPs) and performed a transcriptome-level bioinformatics analysis to clarify their relationship with periodontitis.MethodsTo explore VDR and VDBP polymorphisms, 600 subjects were included, including 307 patients with chronic periodontitis (CP) and 293 healthy controls. Genomic DNA was extracted from peripheral venous blood collected from each subject. A MassARRAY system was used to detect SNPs, including rs1544410G/A (BsmI), rs2228570C/T (FokI), rs7975232G/T (ApaI), rs731236T/C (TaqI), rs739837G/T, rs9729G/T, and rs3847987C/A in the VDR gene, and rs7041A/C in the VDBP gene. Then, we analyzed transcriptome sequencing datas of gingival tissues from two single-cell transcriptome sequencing studies to identify differential expression profiles. The objective was to further explore the potential association between VDR gene and gingival tissues in individuals with CP.ResultsThe regression analysis model revealed a significant relationship between rs739837G/T (P = 0.04) and rs7041A/C (P = 0.03) polymorphisms and CP susceptibility. Subjects carrying the TT genotype of rs739837 showed a decreased risk of developing CP compared to those carrying the GG + GT genotype (OR = 0.53, 95% CI = 0.29–0.99). Individuals carrying the AC + CC genotype of rs7041 showed a reduced risk of developing CP compared to those with the AA genotype (OR = 0.70, 95% CI = 0.51–0.97). Furthermore, allele C of rs7041 was found to have a protective effect against periodontitis (P = 0.03, OR = 0.75, CI = 0.58–0.98). However, no association was found between CP susceptibility and six other 6 SNPs (rs1544410, rs2228570, rs7975232, rs9729, rs731236, and rs3847987). Differential levels of VDR transcription were observed in gingival tissues during CP.ConclusionsVDR genetic variability and transcriptional expression are significant factors affecting susceptibility to CP. These findings suggested that rs739837 TT in VDR and rs7041 A/C in VDBP may be protective against periodontitis.