Variant Genotypes Research Articles

Association of the rs1126616 and rs9138 Variants in the SPP1 Gene among Mexican Patients with Systemic Lupus Erythematosus and Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a multisystem disease considered a prototype of the main autoimmune disease and presents serious complications, such as lupus nephritis (LN), which generates a significant impact on morbidity and mortality. The SPP1 gene encodes the osteopontin (OPN) protein, which plays a crucial role in the regulation of inflammation and immunity. The variants rs1126616 and rs9138 of this gene have been associated with the inflammatory response. The study aims to analyze the association of the rs1126616 and rs9138 variants of the SPP1 gene in SLE Mexican-Mestizo patients without LN (SLE-LN). In this cross-sectional study, a total of 171 genomic DNA samples from SLE patients were clinically confirmed, of which 111 were SLE without LN, 60 were SLE with LN, and 100 healthy individuals were included as reference group. The rs1126616 variant was genotyped using PCR-RFLPs, and the rs9138 variant was genotyped using qPCR TaqMan. The TT genotype, the recessive model [OR 2.76 (95% CI 1.31-5.82), p = 0.011], and the T allele [OR 2.0 (95% CI 1.26-3.16), p = 0.003] of the rs1126616 variant are risk factors for SLE with LN. By contrast, the rs9138 variant did not show statistically significant differences among SLE patients stratified by LN. In our study of SLE Mexican-Mestizo patients with and without NL, demographic and clinical characteristics do not differ from other SLE populations, and the TT genotype of the rs1126616 variant of the SPP1 gene confers a risk factor for the presentation of LN. Otherwise, the rs9138 variant did not show association with NL.

HLA-DPB1 genotype variants predict DP molecule cell surface expression and DP donor specific antibody binding capacity.

The contribution of alloresponses to mismatched HLA-DP in solid organ transplantation and hematopoietic stem cell transplantation (HCT) has been well documented. Exploring the regulatory mechanisms of DPB1 alleles has become an important question to be answered. In this study, our initial investigation focused on examining the correlation between the rs9277534G/A SNP and DPB1 mRNA expression. The result showed that there was a significant increase in DPB1 mRNA expression in B lymphoblastoid cell lines (BLCLs) with the rs9277534GG genotype compared to rs9277534AA genotype. In addition, B cells with the rs9277534GG exhibited significantly higher DP protein expression than those carrying the rs9277534AA genotype in primary B cells. Furthermore, we observed a significant upregulation of DP expression in B cells following treatment with Interleukin 13 (IL-13) compared to untreated B cells carrying rs9277534GG-linked DPB1 alleles. Fluorescence in situ hybridization (FISH) analysis of DPB1 in BLCL demonstrated significant differences in both the cytoplasmic (p=0.0003) and nuclear (p=0.0001) localization of DP mRNA expression comparing DPB1*04:01 (rs9277534AA) and DPB1*05:01 (rs9277534GG) homozygous cells. The study of the correlation between differential DPB1 expression and long non-coding RNAs (lncRNAs) showed that lnc-HLA-DPB1-13:1 is strongly associated with DP expression (r=0.85), suggesting the potential involvement of lncRNA in regulating DP expression. The correlation of DP donor specific antibody (DSA) with B cell flow crossmatch (B-FCXM) results showed a better linear correlation of DP DSA against GG and AG donor cells (R2 = 0.4243, p=0.0025 and R2 = 0.6172, p=0.0003, respectively), compared to DSA against AA donor cells (R2 = 0.0649, p=0.4244). This explained why strong DP DSA with a low expression DP leads to negative B-FCXM. In conclusion, this study provides evidence supporting the involvement of lncRNA in modulating HLA-DP expression, shedding lights on the intricate regulatory mechanisms of DP, particularly under inflammatory conditions in transplantation.

The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population.

Early-onset Type 1 diabetes (EOT1D) is considered a disease subtype with distinctive immunological and clinical features. While both Human Leukocyte Antigen (HLA) and non-HLA variants contribute to age at T1D diagnosis, detailed analyses of EOT1D-specific genetic determinants are still lacking. This study scrutinized the involvement of the HLA class II locus in EOT1D genetic control. We conducted genetic association and regularized logistic regression analyses to evaluate genotypic, haplotypic and allelic variants in DRB1, DQA1 and DQB1 genes in children with EOT1D (diagnosed at ≤5 years of age; n=97), individuals with later-onset disease (LaOT1D; diagnosed 8-30 years of age; n=96) and nondiabetic control subjects (n=169), in the Portuguese population. Allelic association analysis of EOT1D and LaOT1D unrelated patients in comparison with controls, revealed that the rare DRB1*04:08 allele is a distinctive EOT1D susceptibility factor (corrected p-value=7.0x10-7). Conversely, the classical T1D risk allele DRB1*04:05 was absent in EOT1D children while was associated with LaOT1D (corrected p-value=1.4x10-2). In corroboration, HLA class II haplotype analysis showed that the rare DRB1*04:08-DQ8 haplotype is specifically associated with EOT1D (corrected p-value=1.4x10-5) and represents the major HLA class II genetic driver and discriminative factor in the development of early onset disease. This study uncovered that EOT1D holds a distinctive spectrum of HLA class II susceptibility loci, which includes risk factors overlapping with LaOT1D and discriminative genetic configurations. These findings warrant replication studies in larger multicentric settings encompassing other ethnicities and may impact target screening strategies and follow-up of young children with high T1D genetic risk as well as personalized therapeutic approaches.

Contribution of Radiation Sensitive Protein 51 Genotypes to Pterygium Risk in a Taiwanese Population.

In current literature, there is a notable lack of studies investigating the role of radiation-sensitive protein 51 (RAD-51) in pterygium diagnosis. Nevertheless, reports indicate elevated expression levels of RAD-51 among recurrent pterygium cases compared to those with primary pterygium. However, the genomic involvement of RAD-51 has yet to be explored in any population. This study aimed to assess the contribution of RAD-51 genotypes to pterygium risk in a representative Taiwanese population. RAD-51 rs1801320 genotyping was successfully conducted in a Taiwanese cohort comprising 140 pterygium cases and 280 non-pterygium controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. The distribution of RAD-51 rs1801320 genotypes (GG, CG, and CC) in the pterygium group (70.0%, 25.7%, and 4.3%, respectively) did not significantly differ from that in the non-pterygium group (73.6%, 23.6%, and 2.8% for GG, CG, and CC genotypes, respectively; p for trend=0.6337). Carriers of the variant CG and CC RAD-51 rs1801320 genotypes exhibited 1.15- and 1.58-fold increased pterygium risk, respectively (95%CI=0.72-1.84 and 0.53-4.67, p=0.6552 and p=0.5914, respectively). In the dominant model, there appeared to be a slight association between variant genotypes CG and CC and pterygium risk (OR=1.19, 95%CI=0.76-1.87, p=0.0223). Allelic analysis revealed that the RAD-51 rs1801320 variant C allele was not significantly linked to pterygium risk (17.1% versus 14.6%, OR=1.20, 95%CI=0.82-1.78, p=0.3991). Variant genotypes at RAD-51 rs1801320 were firstly identified to associate with susceptibility to pterygium among Taiwanese individuals. Nonetheless, these findings warrant validation in larger and more diverse populations.

Association of genetic polymorphism of glutathione S-transferases with colorectal cancer susceptibility in snuff (Naswar) addicts.

The current study aimed to investigate the relationship between polymorphisms in detoxifying (GSTM1, GSTT1, and GSTP1) genes and their association with colorectal cancer (CRC) in tobacco addicts of Pashtun ethnicity. Polymorphisms in the selected genes were genotyped in a case-control study consisting of 100 histologically confirmed male CRC patients and 100 birth-year and gender-matched healthy controls using the PCR-RFLP method. The GSTM1 null, and GSTT1 null genotypes were significantly contributed to the risk of CRC in the cases (OR= 3.131, 95% CI: 1.451-6.758, P = 0.004, and OR= 3.541, 95% CI: 1.716-7.306, P = 0.001, respectively), whereas the association observed for GSTP1 Val/Val (1.139, 95% CI: 0.356-3.644, P = 0.826) did not show statistical significance. The combined GSTM1 null and GSTT1 null showed a 41-fold increased risk (95% CI: 4.945-351.950, P = 0.001), while, the combined GSTM1 null and GSTP1 Ile/Val or Val/Val variant genotypes exhibited about 3-fold (95% CI: 1.196-7.414, P = 0.019) increased risk to CRC. Similarly, the combined GSTT1 null and GSTP1 Ile/Val or Val/Val variant genotypes showed about a 3-fold (95% CI: 1.285-8.101, P = 0.013) increased risk of CRC. In the combination of three GST genotypes, the GSTM1 null, GSTT1 null, and GSTP1 Ile/Val or Val/Val variant genotypes demonstrated a more than a 22-fold (95% CI: 2.441-212.106, P = 0.006) increased risk of CRC. Our findings suggest that GSTM1 and GSTT1 polymorphism and its combination with GSTP1 may be associated with CRC susceptibility in the Naswar addicted Pashtun population of Khyber Pakhtunkhwa, Pakistan.

Genetic association of the BsmI variant of vitamin D receptor gene with risk of morbid obesity.

The aim of this study was to evaluate the vitamin D receptor (VDR) BsmI variant in morbidly obese patients compared with healthy normal controls. The study included 103 patients with morbid obesity and 120 healthy individuals serving as normal controls. The DNA samples obtained from blood were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The gender, age, smoking status, triglycerides, total cholesterol, insulin, mean body mass index, and frequency of allele and genotype of the BsmI variant in the VDR gene in morbidly obese patients were evaluated. The body mass index of the patients was 47.14 ± 7.19. The VDR B/B, B/b, and b/b genotype frequencies were 27.2% versus 28.3%; 54.4% versus 50%; and 18.4% versus 21.7% in the morbidly obese patients and the control group, respectively. There was no statistically significant difference between patients and control subjects in the genotype and allele distribution of the VDR BsmI variant (p>0.05). Both patients and control genotype frequencies are consistent with Hardy-Weinberg equilibrium. The BsmI variant in the VDR gene may not seem to predispose to morbid obesity in our study population. Further studies with a larger number of subjects are needed to make a more precise evaluation of this relationship.

The characterization and comorbidities of heterozygous Bardet-Biedl syndrome carriers.

Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. Materials and Methods: This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. Results: We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. Conclusion: We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.

The role of polymorphic cytochrome P450 gene (CYP2B6) in B-chronic lymphocytic leukemia (B-CLL) incidence and outcome among Egyptian patients.

Cytochromes P450 (CYPs) play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75% of the total metabolism of commercially available drugs, including chemotherapeutics. The gene expression and enzyme activity of CYPs are variable between individuals, which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics, as well as differences in the efficacy and toxicity of clinically used drugs. This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients, as well as the clinical outcome after receiving cyclophosphamide chemotherapy. DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex- and age-matched healthy individuals. The presence of the CYP2B6*9 (G516T) polymorphism was examined by PCR-based allele specific amplification (ASA). Patients were further indicated for receiving chemotherapy, and then they were followed up. The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models, comprising allelic (T-allele vs. G-allele, OR = 4.8, p < 0.001) and dominant (GT + TT vs. GG, OR = 5.4, p < 0.001) models. Following cyclophosphamide chemotherapy, we found that the patients with variant genotypes (GT + TT) were less likely to achieve remission compared to those with the wild-type genotype (GG), with a response percentage of (37.5% vs. 83%, respectively). In conclusion, our findings showed that the CYP2B6*9 (G516T) polymorphism is associated with B-CLL susceptibility among Egyptian patients. This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

MiR-146a expression and the miR-146a gene variant rs2910164 as diagnostic and prognostic biomarkers of oral cancer

This study aimed to analyze the diagnostic and prognostic significance of miR-146a-5p in oral cancer and the association of the rs2910164 gene variant with miR-146a-5p expression. Thirty-five oral cancer patients participated in the study. Expression of miR-146a-5p in oral cancer, adjacent noncancerous tissue, and the rs2910164 genotype variant were examined by real-time PCR. No difference was observed in miR-146a-5p expression between cancerous and non-cancerous tissues (P=0.272). It was concluded that miR-146a-5p is not a good diagnostic biomarker. There was no difference in miR- 146a-5p expression depending on the rs2910164 genotype. The rs2910164 variant was associated with tumor histological grade (P=0.037), stage (P=0.036), and lymph node status (P=0.025). There was a difference in survival between oral cancer patients with high and low miR-146a-5p expression (P=0.026), but not between patients with the GG and GC genotypes (P=0.400). Oral cancer patients with the wild-type GG genotype and high miR-146a-5p expression had significantly shorter survival when compared to patients with miR-146a-5p expression below the optimal cut-off and the wild-type genotype (P=0.035). A high miR-146a-5p level could be considered a potential biomarker of poor survival in patients with oral cancer, especially in those with the wild-type GG genotype of the rs2910164 variant.

Single nucleotide variants in the CCL2, OAS1 and DPP9 genes and their association with the severity of COVID-19 in an Ecuadorian population.

COVID-19 has a broad clinical spectrum, ranging from asymptomatic-mild form to severe phenotype. The severity of COVID-19 is a complex trait influenced by various genetic and environmental factors. Ethnic differences have been observed in relation to COVID-19 severity during the pandemic. It is currently unknown whether genetic variations may contribute to the increased risk of severity observed in Latin-American individuals The aim of this study is to investigate the potential correlation between gene variants at CCL2, OAS1, and DPP9 genes and the severity of COVID-19 in a population from Quito, Ecuador. This observational case-control study was conducted at the Carrera de Biologia from the Universidad Central del Ecuador and the Hospital Quito Sur of the Instituto Ecuatoriano de Seguridad Social (Quito-SUR-IESS), Quito, Ecuador. Genotyping for gene variants at rs1024611 (A>G), rs10774671 (A>G), and rs10406145 (G>C) of CCL2, OAS1, and DPP9 genes was performed on 100 COVID-19 patients (43 with severe form and 57 asymptomatic-mild) using RFLP-PCR. The genotype distribution of all SNVs throughout the entire sample of 100 individuals showed Hardy Weinberg equilibrium (P=0.53, 0.35, and 0.4 for CCL2, OAS1, and DPP9, respectively). The HWE test did not find any statistically significant difference in genotype distribution between the study and control groups for any of the three SNVs. The multivariable logistic regression analysis showed that individuals with the GG of the CCL2 rs1024611 gene variant had an increased association with the severe COVID-19 phenotype in a recessive model (P = 0.0003, OR = 6.43, 95% CI 2.19-18.89) and for the OAS1 rs10774671 gene variant, the log-additive model showed a significant association with the severe phenotype of COVID-19 (P=0.0084, OR=3.85, 95% CI 1.33-11.12). Analysis of haplotype frequencies revealed that the coexistence of GAG at CCL2, OAS1, and DPP9 variants, respectively, in the same individual increased the presence of the severe COVID-19 phenotype (OR=2.273, 95% CI: 1.271-4.068, P=0.005305). The findings of the current study suggests that the ethnic background affects the allele and genotype frequencies of genes associated with the severity of COVID-19. The experience with COVID-19 has provided an opportunity to identify an ethnicity-based approach to recognize genetically high-risk individuals in different populations for emerging diseases.

ПРОЯВЛЕНИЯ ЭПИДЕМИЧЕСКОГО ПРОЦЕССА ЭНТЕРОВИРУСНОЙ ИНФЕКЦИИ В СУБЪЕКТАХ ДАЛЬНЕВОСТОЧНОГО И СИБИРСКОГО ФЕДЕРАЛЬНЫХ ОКРУГОВ РОССИЙСКОЙ ФЕДЕРАЦИИ В 2023 Г. ПРОГНОЗ ЗАБОЛЕВАЕМОСТИ ЭНТЕРОВИРУСНОЙ ИНФЕКЦИЕЙ НА 2024 Г.

The annual increase in the incidence of enterovirus infection (EVI) in the population of the Far East and Eastern Siberia determines the need for constant epidemiological surveillance of EVI using molecular typing of enteroviruses.In 2023, a significant excess of the long-term average incidence rate of EVI was noted in 8 of the 16 analyzed territories of the Far Eastern and Siberian federal districts. The main clinical forms of EVI were herpangina and exanthema forms. Among the identified types of enteroviruses in 2023, coxsackievirus A6 predominated. Phylogenetic analysis revealed the circulation of a new variant of the eC2 genotype of the ECHO30. The calculation of prognostic indicators showed that an increase in EVI incidence in 2024 is expected in five analyzed territories. The manifestations of the EVI epidemic process in the territories of the Far Eastern and Siberian federal districts in 2023 were influenced by the active circulation of the coxsackievirus A6 and the emergence of a new ECHO30 genovariant. In the territories with high EVI incidence rates predicted for 2024, attention should be paid to the timely organization of epidemic control measures.

Impacts of Matrix Metalloproteinase-9 Promoter Genotypes on Asthma Risk.

The overexpression of matrix metalloproteinase-9 (MMP9) has been observed in asthmatic patients, yet the role of MMP9 genotype in determining asthma susceptibility remains unresolved. This study aimed to elucidate the contribution of MMP9 promoter rs3918242 genotype to asthma risk in Taiwan. A cohort comprising 453 non-asthmatic healthy controls and 198 asthmatic cases was assembled, and the MMP9 rs3918242 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism methodology. Our findings indicated that people carrying the variant CT or TT genotype of MMP9 rs3918242 did not demonstrate an elevated risk of asthma compared to wild-type CC carriers (odds ratio=1.28 and 1.72, 95% confidence interval=0.87-1.87 and 0.72-4.13; p=0.2417 and 0.3201, respectively). Furthermore, individuals carrying the T allele at MMP9 rs3918242 did not exhibit a higher risk of asthma than those carrying the C allele (odds ratio=1.31, 95% confidence interval=0.96-1.79, p=0.0869). Interestingly, a positive association was observed between MMP9 rs3918242 CT or TT genotypes and the severity of asthma symptoms among asthmatic patients (p=0.0035). Although the T allele at MMP9 rs3918242 was not associated with asthma risk, it may serve as a predictor for asthma symptom severity. These findings warrant validation in larger and more diverse populations to further elucidate the significance of MMP9 in asthma etiology.

Superoxide Dismutase (rs2070424, rs4880, rs2536512) and Catalase (rs794316, rs1001179) SNPs and their Association with Breast Cancer Risk: Findings from a Hospital Based Case-Control Study.

The antioxidant enzymes are important cellular components involved in detoxification of reactive oxygen species (ROS) and protect cells from ROS induced oxidative damage. Single nucleotide polymorphisms (SNPs) of antioxidant enzyme coding genes such as superoxide dismutase (SOD) and catalase (CAT) may alter the enzyme activity which can influence susceptibility towards carcinogenesis. Therefore, the present study was planned to investigate possible SNPs of SOD (SOD1 (Cu,Zn-SOD), SOD2(Mn-SOD), SOD3(EC-SOD) and CAT genes and their possible association with breast cancer risk in rural Indian women. In this case-control study, the association of SOD and CAT gene polymorphism was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The study was conducted among 400 clinically breast cancer patients and 400 healthy women in a population of South-Western Maharashtra. The logistic regression analysis was carried out to calculate Odds ratio (OR) with 95% confidence interval and p-value, where p ≤0.05 was considered as statistically significant. The results of analysis of genotype frequency distribution showed significant association of rs4880 SNP of Mn-SOD with BC risk at homozygous variant (CC/CC) genotype (OR 2.46; 95%CI, 1.61-3.75; p<0.0001) and corresponding frequency of variant (C) allele (OR 1.53; 95%CI, 1.25-1.86; p<0.0001). In CAT gene polymorphisms the variant (T/T) was increased significantly in BC cases as compared to controls (OR 3.45; 95%CI, 2.17-5.50; p<0.0001) along with its variant (T) allele (OR 2.01; 95%CI, 1.63-2.48; p<0.0001). The results implied that, C/C genotype of SOD2-1183T/C polymorphism and T/T genotype of CAT-262 C/T polymorphism may be associated with an increased breast cancer risk. However, SOD1-251 A/G and SOD3-172 G/A polymorphisms did not show any significant difference in variant homozygous genotypes of patients compared to controls.

Genetic Polymorphisms of XPC, XPD, XPG Genes and their Association with Radiotherapy Induced Toxicity among Head and Neck Cancer Patients: A Hospital Based Study from Maharashtra.

The present study was planned to investigate possible association of single nucleotide polymorphisms (SNPs) of nucleotide excision repair (NER) genes such as XPC, XPD, XPG with acute radiation induced toxicities such as skin reactions and oral mucositis in normal tissue from head and neck cancer (HNC) patients receiving radiotherapy. Methods: Two hundred and fifty HNC patients receiving radiotherapy were enrolled in this study and the acute toxicity reactions and radiation response were recorded. Association of SNPs rs2228001 of XPC, rs238406, rs13181 of XPD and rs17655 of XPG gene with normal tissue reactions in the form of dermatitis and mucositis were studied by PCR-RFLP and direct DNA sequencing. The results of univariate analysis of SNPs of XPC, XPD and XPG showed that XPC polymorphism at codon 939 of exon 15 (A>C) was not associated with dermatitis (OR=0.30, 95% CI: 0.06-1.39; p=0.125), or oral mucositis (OR=1.14, 95% CI: 0.41-3.20; p=0.793). The XPD codon 156 of exon 6 (C>A) and codon 751 of exon-23 A>C) polymorphism showed no association with radiosensitivity in HNC patients (OR=1.50, 95% CI: 0.60-3.71; p=0.080) for dermatitis, (OR=1.54, 95% CI: 0.66-3.61; p=0.312) for oral mucositis. The 1104 Asp variant genotype or allele of XPG (OR=1.35 95% CI: 0.50-3.64; p=0.541) showed no association with degree of radiotherapy associated dermatitis or mucositis (OR=0.80, 95% CI: 0.32-2.03; p=0.648) in HNC patients. The variant C allele of 2920 A/C genotype of XPC gene at codon 939 of exon 15, found protective with developing skin reactions with grade >1 (OR=0.60, 95% CI: 0.36-0.97; p=0.039) in HNC patients treated with radiotherapy. The results obtained in this study concluded that the SNPs rs2228001of XPC, rs238406, rs13181 SNPs of XPD and rs17655 SNP of XPG are not associated with normal tissue toxicity in HNC patients treated with radiotherapy. Radiotherapy with high radiation dose was significantly associated with oral mucositis in response to radiotherapy.

Vitamin D status in connection with VDR and GC genes polymorphism in coal mining workers

Vitamin D is a unique compound that can enter the human body not only with food, but also be synthesized in the skin under the influence of ultraviolet radiation. Individual differences in the need for this vitamin may be associated with the carriage of polymorphic variants of genes that implement its biological effects, which include VDR BsmI C>T (rs1544410), VDR TaqI A>G (rs731236) and GC rs2282679 T>G. At risk for vitamin D deficiency are workers in the coal mining industry, whose working conditions combine limited insolation and a pronounced deficiency of vitamins in the diet. The purpose of the study was to assess vitamin D plasma level in coal mining workers depending on the carriage of polymorphic variants of the VDR BsmI C>T (rs1544410), VDR TaqI A>G (rs731236) and GC rs2282679 T>G genes and professional working conditions. Material and methods. The study included 154 coal mining workers. The main group consisted of 100 workers associated with the underground nature of work, the comparison group - 54 ground workers of the enterprise. In all individuals, the level of 25-hydroxyvitamin D in blood plasma was determined by enzyme-linked immunosorbent assay and genotyping was performed for three polymorphic loci: VDR rs1544410, rs731236, GC rs2282679 by real-time PCR. Results. A statistically significant decrease in the concentration of plasma vitamin D in the underground workers was revealed, compared with the level of this vitamin in ground workers of the enterprise (p=0.037). Underground workers - carriers of the CT genotype of the VDR rs1544410 gene, AG of the VDR rs731236 gene and TT of the GC rs2282679 gene had a lower 25(OH)D level in blood plasma compared to owners of similar genotype variants in the comparison group (p<0.05). Among ground workers, carriers of the TT genotype of the GC rs2282679 gene had a significantly higher vitamin D plasma level compared to carriers of the TG and GG genotypes (p=0.02). An association of the GC gene with vitamin D level in blood plasma was revealed according to a dominant model of inheritance (OR=0.47, 95% CI 0.23-0.97; p=0.037, for owners of the TT genotype, compared with carriers of the TG+GG genotypes). Conclusion. The development of personalized diets based on individual genetic status may be of great importance for the prevention of diseases associated with vitamin D deficiency in individuals at risk.

PVUII (RS2234693) POLYMORPHISM OF THE ESTROGEN RECEPTOR ALPHA GENE IN WOMEN FROM SUMY OBLAST, UKRAINE, WITH ENDOMETRIAL HYPERPLASTIC PROCESS

Introduction. The endometrial hyperplastic process is an estrogen-dependent benign condition of the uterus, which is frequently a cause of infertility, ovarian-menstrual cycle disorders, and malignant transformation into uterine cancer. The effect of estrogen on the endometrium is realized through the estrogen receptor alpha. It is manifested by a whole range of biological changes, including cell reproduction and growth, tissue development, etc. Estrogen receptor alpha is encoded by the ESR1 gene, which is located on chromosome 6q25 and has eight exons and seven introns. Today, about 9,000 polymorphisms of the ESR1 gene have been described, some of which are associated with gene activity changes. Such functional polymorphisms include the PvuII polymorphism (rs2234693), which occurs due to the substitution of thymine (T) for cytosine (C) in the first intron of the gene. Objective. The purpose of this study was to assess the frequency of allelic variants of the estrogen receptor alpha gene for the PvuII polymorphism in patients with endometrial hyperplastic process living in the Sumy Oblast of Ukraine and to study its relationship with the histological variant of endometrial hyperplastic process, anthropometric parameters, age categories, medical history, and concomitant diseases. Materials and Methods. Genomic DNA was isolated from blood samples of 95 women with endometrial hyperplastic processes and 80 healthy women. The rs2234693 polymorphism was studied using a polymerase chain reaction with subsequent restriction fragment length polymorphism analysis (PCR-RFLP). The data were processed and statistically analyzed with Microsoft Excel and SPSS Statistics 29.0 for Windows software package. Descriptive statistics, Student's test, ANOVA method, and Pearson's chi-squared test were used in this study. Results with P &lt; 0.05 were considered statistically significant. Results. The distribution of genotype variants for the PvuII polymorphism of the ESR1 gene in women with endometrial hyperplastic process was: homozygotes for the major allele (T/T) – 31.6%, heterozygotes (T/C) – 49.5%, homozygotes for the minor allele (C/C) – 18.9%; in the control group, these values were 30%, 52.5%, and 17.5%, respectively. There was no difference in the distribution of genotypes in patients with endometrial hyperplastic processes and healthy women (χ2 = 0.163, P = 0.922). No associations were found between the PvuII polymorphism and the histological variant of endometrial hyperplastic processes (χ2 = 4.14, P = 0.387), anthropometric parameters (P &gt; 0.05), age (χ2 = 2.98, P = 0.560), medical history (P &gt; 0.05), or concomitant genital and extragenital conditions (P &gt; 0.05). Conclusions. There was no difference in the distribution of T/T, T/C, and C/C genotypes for the PvuII polymorphism in the estrogen receptor alpha gene between patients with endometrial hyperplastic process and the control group. There was no correlation between the genotype variant for the studied polymorphism and the histological variant of the endometrial hyperplastic process, anthropometric parameters, age, medical history, concomitant genital and extragenital conditions in patients of the Sumy Oblast, Ukraine.

Initial screening of the rs104893657 variant of the PAX8 gene in women with hypothyroidism from Northeastern Slovakia.

Thyroid diseases are among the most common endocrinopathies and metabolic disorders. Hypothyroidism is caused by insufficient production of thyroid hormones with a higher prevalence in women. Causes for the development of endocrine diseases may be mutations in genes that encode peptide hormones. The aim of this scientific study was to determine the genotype and allele frequencies of the rs104893657 variant of the PAX8 gene and to determine the genotype versus phenotype association. The study population consisted of 135 women from northeastern Slovakia who were divided on the basis of screening into two groups: a control group without diagnosed hypothyroidism (CG = 67) and a group of women with hypothyroidism (HY = 68). Biochemical markers - thyroid-stimulating hormone (TSH), prealbumin (PREA), calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) were determined using Cobas Integra 400 plus, Cobas e411 analysers (Roche). Genotyping was performed using TaqMan® SNP Genotyping Assay instrument 7500 Fast Real-Time PCR Systems (Applied Biosystem). Student's t-test revealed a statistically significant difference between CG and HY in biochemical parameters: TSH (p < 0.001), P (p = 0.008). By Chi-square test we found no statistically significant difference in the representation of genotypes (p = 0.788) in the rs104893657 polymorphism of PAX8 gene. The T allele was not associated with hypothyroidism in Slovak women (p = 0.548). In CC genotype we found statistically significant difference between CG and HY in parameters TSH (p < 0.001) and P (p = 0.006). The mutant T allele was detected at low frequency in both groups of women studied. The association of the T allele with the development of hypothyroidism in Slovak women was not confirmed. The results of this work provide initial information on the distribution of genotypes and alleles in the studied variant of PAX8 gene in the Slovak female population.

Quit Attempts Among Smokers and its Association with CYP2A6 (rs56113850) Polymorphisms

Introduction: Nicotine serves as the primary addictive component of tobacco. While it is not a carcinogen itself, it plays an important role in encouraging smoking and ongoing exposure to numerous carcinogenic substances found in tobacco. The half-life of nicotine tends to be extended in individuals with reduced P450 2A6 activity, and smokers with lower enzyme activity frequently reduce either the intensity of their smoking or the number of cigarettes they consume when compared to individuals with 'normal' enzyme activity. Hence, a study assessed CYP2A6 polymorphisms and quit attempts among smokers. Materials and methods: 5ml of salivary samples were collected from 100 smokers and 100 nonsmokers who had visited Saveetha Dental College in April- May 2023. DNA isolation was done, followed by PCR analysis and Amplification with RFLP. Quit attempts, duration of quit attempts, and methods employed for smoking abstention were assessed using a questionnaire. The statistical association between quit attempts and CYP2A6 (rs56113850) polymorphism was done using the Chi-square test. Results: About 27.9% of smokers had an attempt to quit smoking previously; the rest of smokers (72.1%) did not make an attempt to quit the habit. About 74% smokers have the normal allele (T), the rest 26% have a variant allele (C), about 73% of non-smokers have a normal allele, and the rest 27% have a variant allele. Association between CYP2A6 allele variants and interest to quit scale showed that the normal genotype has a higher scale of interest in quitting tobacco, and the homozygous variant genotype shows the least interest towards quitting tobacco usage, suggesting that there is an association between gene polymorphism and quit attempts. Conclusion: In the present study, there is an association between quit attempts and CYP2A6 polymorphisms among the smokers who had visited the dental hospital. However, the association is not statistically significant.

INFLUENCE OF LGALS-3 GENE POLYMORPHISM (rs2274273) ON THE PLASMA LEVELS OF GALECTIN-3 IN WOMEN WITH ESSENTIAL HYPERTENSION AND CHRONIC HEART FAILURE IN RESIDENTS OF THE PODILLYA REGION OF UKRAINE

Background. Individual genetic features can influence to formation of structural and functional changes in organs during EH and encourage the search for biological markers of the state of the myocardium and conclusions about their diagnostic effectiveness.&#x0D; Aim: to improve the early diagnosis of changes in the structure and function of the myocardium and the formation of prerequisites for chronic heart failure (CHF) in women with EH carriers of various polymorphic variants of the LGALS-3 gene (rs2274273), based on galectin-3 plasma level.&#x0D; Materials and methods. 180 postmenopausal women, average age 57,34±0,45, residents of the Podillya region of Ukraine were examined. The main group included 113 women with EH, of which 62 people had EH II, 51 people - EH with CHF C stage according to the ESH 2023 classification. The control group included 67 women without signs of cardiovascular pathology. In addition to the general clinical examination, the research used the enzyme immunoassay method to determine the level of galectin-3 in blood plasma, genotyping of the LGALS3 gene (rs2274273) by means of polymerase chain reaction, and ultrasound of the heart. The statistical processing of the obtained results was carried out using the package of statistical programs SPSS, STATISTICA v. 10.0. Using the MedCalc Software Ltd. Odds ratio calculator (https://www.medcalc.org/calc/odds_ratio.php) the conformity of the frequency distribution of genotypes in the studied population to the Hardy-Weinberg equilibrium was checked and calculated the odds ratio (OR) of the development of left ventricular myocardial hypertrophy (LVH) and CHF on the background of EH. The threshold levels of galectin-3 in blood plasma for the diagnosis of LVH and CHF were calculated using the ROC analysis method.&#x0D; Results. During study the frequency distribution of genotype variants of the galectin-3 gene (rs2274273) among women residents of the Podillya region of Ukraine, it was found that both in people without cardiovascular pathology and in patients with EH II and EH III, the GA genotype predominates, although there is a significant difference between the frequency of occurrence genotypes GA and GG are not noted (p&gt;0.05). The AA genotype variant is significantly less frequent than both the GA and GG genotypes (p&lt;0.01). The frequency distribution of genotype variants corresponds to the Hardy-Weinberg equilibrium. Moreover, the ratio between genotypes in patients of different stages of EH does not reliably differ from that in the control group. However, in EH complicated by CHF among patients with LVEF &lt; 50% A allele carriers significantly predominate compared to GG homozygotes (79.31%, n=23 vs. 20.69%, n=6). In patients with EH, it was found that the concentration of galectin-3 in blood plasma in carriers of the A allele is significantly higher than in carriers of the GG genotype: EH without CHF - 16.82±0.54 ng/ml vs. 12.82±0.54 ng/ml (p&lt;0.01); EH with CHF – 35.70±1.53 ng/ml vs. 25.39±1.38 ng/ml (p&lt;0.001). The threshold levels of galectin-3 plasma concentrations, which indicate the presence of LVH and CHF, are significantly higher in carriers of the A allele than in carriers of the GG genotype.&#x0D; Conclusion. The carriers of the A allele of the LGALS3 gene (rs2274273) have a greater chance of developing CHF with a LVEF &lt; 50% (OR 4.60; 95% CI 1.35 - 15.73 z statistic 2.43 p&lt;0.01 χ2=6 .28; p=0.0122) and correspondingly higher levels of galectin-3 in blood plasma compared to carriers of the GG genotype.

The Contribution of DNA Ligase 4 Polymorphisms to Colorectal Cancer.

While numerous biomarkers associated with genetic susceptibility to colorectal cancer (CRC) have been identified and validated through epidemiological studies, the specific influence of DNA ligase 4 (Lig4) genotypes remains unexplored. This study aimed to elucidate the hitherto unexamined relationship between Lig4 genotypes and CRC risk. The genotypes of Lig4 rs1805388 were determined applying the polymerase chain reaction-restriction fragment length polymorphism methodology. The potential association between these genotypes and CRC risk was assessed in a Taiwanese population comprising 362 CRC cases and an equal number of age- and sex-matched controls. In the genotypic analysis, the distribution of CC, CT, and TT genotypes for Lig4 rs1805388 among CRC cases was 54.7%, 38.1%, and 7.2%, respectively. This distribution was not significantly different from the controls, which exhibited genotypic frequencies of 57.2%, 36.7%, and 6.1%, respectively (p for trend=0.7314). Analysis of allelic distribution indicated that individuals carrying the T allele of Lig4 rs1805388 displayed a slightly elevated CRC risk compared to those carrying the C allele (odds ratio=1.10, 95% confidence interval=0.87-1.39, p=0.4685). The variant genotypes of Lig4 rs1805388 may not serve as predictive markers for CRC risk in the Taiwanese population.