Rs1800629 Polymorphism Research Articles

Association of Matrix Metalloproteinase-1 Promoter Genotypes With Endometriosis Risk.

Over-expression of matrix metalloproteinase-1 (MMP-1) has been suggested as a biomarker for endometriosis. However, the genetic influence of MMP-1 in the pathogenesis of endometriosis remains unclear, with its role yet to be fully elucidated. This study aimed to investigate the association between MMP-1 rs1799750 promoter polymorphisms and the risk of developing endometriosis. This hospital-based case-control study included 203 women diagnosed with endometriosis and 636 age-matched controls. Genotyping of the MMP-1 rs1799750 polymorphism was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Among the patients with endometriosis, the distribution of genotypes 2G/2G, 2G/1G, and 1G/1G at MMP-1 rs1799750 was 52.7%, 41.4%, and 5.9%, respectively. This distribution significantly differed from that of the control group, which exhibited frequencies of 41.3%, 48.3%, and 10.4%, respectively (p for trend=0.0092). In the dominant model, carriers of the 2G/1G and 1G/1G genotypes had a reduced prevalence in the endometriosis group compared to 2G/2G carriers [odds ratio (OR)=0.63, 95% confidence interval (95%CI)=0.46-0.87, p=0.0058]. Additionally, the 1G allele frequency in the endometriosis group was 26.6%, significantly lower than the 34.5% observed in controls (OR=0.69, 95%CI=0.54-0.88, p=0.0037). The 1G allele of MMP-1 rs1799750 is associated with reduced susceptibility to endometriosis in the Taiwanese population. These results highlight the potential of MMP-1 rs1799750 polymorphism as a protective genetic marker, warranting further investigations to explore its genotype-phenotype correlation and underlying biological mechanisms.

STAT4 gene polymorphism may be associated with microscopic polyangiitis susceptibility in a Chinese Guangxi population: A case-control analysis based on propensity score matching.

Microscopic polyangiitis (MPA) is a severe multisystem autoimmune disease featured by small-vessel vasculitis with few or no immune complex, also has a significant genetic predisposition. Growing evidence has confirmed that STAT4 gene is tightly associated with multiple autoimmune diseases, but its contribution to MPA onset is still elusive. The aim was to investigated the association between STAT4 gene polymorphisms (rs7572482, rs7574865 and rs12991409) and MPA susceptibility in a Guangxi population of China. 260 MPA patients and 295 healthy adult volunteers were selected, 1:1 propensity score matching (PSM) was performed to control potential confounding variables, then 199 MPA patients and 199 healthy adult volunteers matched in gender, ethnicity and age were included in this study. High-throughput sequencing and multiplex PCR were applied to detect the target STAT4 SNPs. SHEsis and SNPstats were used to evaluated the allele frequency, genotype frequency, linkage disequilibrium (LD), haplotype, and the association between SNPs and the MPA susceptibility in multiple genetic models. SNP-SNP interactions were explored based on generalized multifactor dimensionality reduction (GMDR) algorithm. Some clinical indicators, such as renal pathology and therapeutic effects, were collected and compared. The allele and genotype frequencies of rs7574865 displayed significant diversities between case group and control group (p < 0.05). Strong LD was found between rs7572482 and rs12991409 (D'=0.9). The haplotype GGT was related to a reduced risk of MPA (OR = 0.661, 95 %CI: 0.469-0.931, p = 0.017), and haplotype GTT might perform an increased risk of MPA (OR = 1.922, 95 %CI: 1.225-3.015, p = 0.004). Rs7574865 polymorphism was associated with an increased risk of MPA in codominant model (OR:2.03; p = 0.0093), dominant model (OR: 1.88p = 0.0023), and overdominant model (OR:1.57; p = 0.027). In Han and male subgroups, rs7574865 polymorphism dramatically increased the MPA risk. GMDR suggested that STAT4 rs7574865 and PTPN22 rs3811021 composed the most risk combinations (p = 0.0010). Moreover, renal pathology, Birmingham vasculitis activity score (BVAS), and alanine aminotransferase (ALT) might be linked with STAT4 gene polymorphisms (p < 0.05). The genetic polymorphism of STAT4 may be associated with MPA susceptibility and renal pathological classification in Chinese Guangxi population; the T allele of rs7574865 may be an important risk factor for MPA.

"Association of vitamin D blood deficiency and the rs731236 polymorphism vitamin D receptor with primary knee osteoarthritis in subjects from Mexico".

Vitamin D deficiency is a public health problem worldwide. Some studies have associated serum vitamin D deficiency with knee osteoarthritis. Additionally, some vitamin D receptor polymorphisms have been linked to knee osteoarthritis. This study analyzed the associations among the rs731236 polymorphism of the vitamin D receptor, blood levels of vitamin D and primary knee osteoarthritis in a population from northern Mexico.A case‒control study was conducted from November 2023 to June 2024 with 449 unrelated participants. The vitamin D concentration in the blood was measured semiquantitatively. The presence of vitamin D receptor gene polymorphism genotypes (rs731236) was determined via the rhAmpTM SNP Assay methodology. We used the chi-square test to compare the groups and odds ratios with confidence intervals to calculate risk.In the presence of vitamin D deficiency, subjects showed a 1.5-fold increased risk of primary knee osteoarthritis (59.5%; p = 0.001). Notably, this association remained significant for subjects carrying the AA and AG genotypes and in a dominant model (60.0%, p = 0.023; 61.1%, p = 0.008 and 59.0%, p = 0.042, respectively), after including a multivariate association model.Our study identified a high prevalence of Vitamin D deficiency among individuals with primary knee osteoarthritis. This study suggests a potential association between deficient levels of vitamin D and primary KOA in carriers of the AA and AG rs731236 genotypes. Key Points • We observed a significant 1.5-fold increased risk of primary knee osteoarthritis in the presence of vitamin D deficiency. • Vitamin D deficiency is significantly associated with primary knee osteoarthritis in carriers of AA and AG genotypes of rs73123.

Association of -607C/A (rs1946518) and -137G/C (rs187238) polymorphisms and immune response in radiation-exposed workers

Purpose Interleukin-18, transforming growth factor-β, and superoxide dismutase are important cytokines and antioxidants in protecting the body from damage caused by radiation exposure through an immune response mechanism. Genetic polymorphisms −607 C/A and −137 G/C are thought to affect the IL-18 cytokine in carrying out its function as a biomarker to indicate adverse conditions due to radiation. The purposes of this study were to investigate the association between 607 C/A and −137 G/C SNPs on the concentrations of IL-18, and to measure TGF-β and SOD activity in radiation workers and control group. Material and method We enrolled 40 radiation workers and 40 non-radiation workers as a control group. We determined genotype distribution of −607 C/A and −137 G/C SNPs and their correlation with IL-18 concentration by using PCR-RFLP method. We also measured the IL-18, TGF-β concentration, and SOD activity by using Elisa assay. Results and conclusion No relationship was found between −607 C/A and −137 G/C on IL-18 concentrations in all genotype groups, and no significant difference in IL-18 and TGF-β concentrations in the radiation worker and control groups. Significant differences were found only in lower SOD activity in radiation workers compared to controls. The −607 C/A and −137 G/C did not significantly correlate with IL-18 cytokine production in all genotypes. There was no significant difference between IL-18 and TGF-β concentrations in the radiation worker and control groups. However, there was a very significant decrease in the SOD activity of the radiation workers by 3.31 times compared to the controls.

Assessment of the impact of VDR polymorphisms on selected hormonal, metabolic and mineral balance markers in young women with hyperandrogenism.

Hyperandrogenism is a frequently recognized endocrine imbalance in which there is excessive production of androgens. The purpose of the study was to investigate the impact of vitamin D receptor (VDR) gene polymorphisms on chosen bone metabolism and biochemical parameters in women with hyperandrogenism. Eighty young females with hyperandrogenism were enrolled in the study, in whom selected parameters of bone turnover, endocrine and metabolic parameters were determined. Two polymorphisms of the VDR gene were analyzed: rs731236 (TaqI) and rs1544410 (BsmI), using real-time polymerase chain reaction (PCR). Statistical tests were performed in this research with the program SPSS Statistics 17.0 for Windows. The rs731236 and rs1544410 polymorphisms of the VDR gene turned out to be statistically significantly related to the concentration of insulin determined in the 60 'glucose tolerance test. There was no relationship between the studied polymorphisms of the VDR gene and the determined parameters of bone metabolism and other biochemical parameters. The research presented that VDR gene variants may influence disturbances in carbohydrate metabolism in young women with hyperandrogenism.

The VDR rs1544410 and rs11568820 Variants and the Risk of Osteoporosis in the Polish Population.

Vitamin D affects bone metabolism and calcium-phosphate metabolism. Its deficiency leads to bone mineralization disorders and is the cause of abnormal skeletal development from fetal life to the period of completed skeletal growth. In later periods of life, vitamin D deficiency leads to bone metabolism disorders, i.e., osteoporosis. Disturbance of the balance between osteoblasts responsible for bone formation and osteoclasts associated with bone resorption results in reduced bone mass and bone weakening, and consequently leads to susceptibility to fractures. Analysis of genetic variants of the vitamin D receptor (VDR) concerns their relationship with metabolic bone diseases, and the results of previous studies assessing the relationship of polymorphisms with bone mineral density, fracture risk, or osteoporosis are not clear. Therefore, the aim of our study was to determine the effect of rs1544410 and rs11568820 polymorphisms of the VDR gene on the risk of developing osteoporosis in the Polish population. The study included 197 women with osteoporosis, 98 women with osteopenia, and 147 healthy controls. The real-time PCR method was used to determine the rs1544410 and rs11568820 polymorphisms of the VDR1 gene. Analysis of the results in the group with osteopenia showed that for the rs1544410 polymorphism, heterozygous GA genotypes occurred in 37.8% of the study group and 47.6% of the controls (OR = 0.60; 95%CI: 0.34-1.05), and homozygous AA in 15.3% of the study group and 17.0% of the controls (OR = 0.68; 95%CI: 0.32-1.44) (p = 0.185, AIC = 332.4; AIC-Akaike information criterion). The best model for this variant turned out to be the dominant model OR = 0.62; 95%CI: 0.37-1.04; p = 0.071, AIC = 330.5. In the case of the rs11568820 polymorphism of the VDR gene, the GG genotype was more common in women with osteopenia compared to controls (75.5% vs. 70.1%). Genotypes containing at least one mutant A allele were present in 24.5% of women with osteopenia and 29.9% of controls (OR = 0.76; 95%CI: 0.43-1.36; p = 0.349; AIC = 332.9). Analyzing the rs1544410 polymorphism in women with osteoporosis, the GA genotype was present in 42.1% of the study group and 47.6% of patients with normal bone density (OR = 0.74; 95%CI: 0.46-1.19), and the AA genotype in 15.7% of the study group and 17.0% of controls (OR = 0.78; 95%CI: 0.41-1.46) (p = 0.441). In the case of the rs11568820 polymorphism, the GA genotype occurred in 22.3% of the study subjects and 27.2% of the control patients (OR = 0.76; 95%CI: 0.46-1.25), and the AA genotype in 2.0% of the study subjects and 2.7% of the controls (OR = 0.69; 95%CI: 0.17-2.83) (p = 0.511). For both variants, the model with the lowest AIC value was the dominant model, in which for the rs1544410 variant OR = 0.75; 95%CI: 0.48-1.17; p = 0.203; AIC = 472.0 was obtained, while for rs11568820-OR = 0.75; 95%CI: 0.47-1.22; p = 0.250; AIC = 472.3. The obtained results indicate that the rs1544410 and rs11568820 polymorphisms of the VDR gene do not affect the development of osteoporosis in the Polish population.

Interleukin-1β rs16944 and rs1143627 polymorphisms and risk of developing major depressive disorder: A case-control study among Bangladeshi population.

Epidemiological research suggests that altered levels of cytokine are associated with pathophysiology and the development of major depressive disorder (MDD). Based on earlier study, IL-1β rs16944 and rs1143627 polymorphisms may increase the risk of depression. Here, we aimed to evaluate the correlation between these polymorphisms and MDD susceptibility among the population in Bangladesh. Blood samples were collected from 100 MDD patients and 70 matched controls. Study participants were evaluated by DSM-5 criteria and PCR-RFLP method were applied for genotyping. The IL1β rs1143627 and rs16944 polymorphisms were found to have a significant association with the risk of MDD. In case of rs1143627 CT heterozygous genotype (OR = 2.22, 95% CI = 1.08-4.55, p-value = 0.029) and combined CT+TT (OR = 2.35, 95% CI = 1.15-4.79, p-value = 0.019) genotype was strongly associated with the increased risk of MDD in comparison to CC common genotype. Moreover, the over-dominant model indicated a 2.15-fold higher risk for MDD development (OR = 2.15, 95% CI = 1.05-4.40, p-value = 0.036). On the other hand, the IL1β rs16944 polymorphisms revealed that the TC+CC combined genotype in the dominant model showed a 2.06-fold increased risk for MDD development compared to the TT common homozygote (OR = 2.06, 95% CI = 1.06-3.99, p-value = 0.032). Studies suggests that IL1β rs16944 and rs1143627 polymorphisms are associated with an increased risk of MDD. These findings will provide us with valuable insights into the pathophysiology of MDD.

Interleukin-17A and Interleukin-17F Gene Polymorphisms in Egyptian Patients with Chronic Hepatitis C and Hepatocellular Carcinoma.

Interleukin IL-17A and IL-17F are critical cytokines involved in inflammatory processes. Genetic variations in IL-17A and IL-17F might be linked to chronic hepatitis C (CHC) and an increased risk of hepatocellular carcinoma (HCC), a cancer associated with long-term inflammation. This study aims to examine the relationship between specific polymorphisms in IL-17A (rs2275913) and IL-17F (rs763780) and their association with HCV-related HCC in an Egyptian population. Authors conducted a case-control study involving 52 patients with chronic hepatitis C, 49 patients with HCV-related HCC, and 51 healthy controls. The study assessed the connection between the IL-17A rs2275913 and IL-17F rs763780 polymorphisms and chronic hepatitis C patients. Genotyping was performed using real-time PCR with TaqMan MGB-probe allelic discrimination. No significant differences in genotype and allele frequencies for IL-17A rs2275913 and IL-17F rs763780 were observed between CHC or HCC patients and control subjects. However, significant associations were found indicating an increased risk of HCC linked to CHC: the GG genotype of IL-17A rs2275913 in a recessive model (P = 0.0129); and CT and CT + CC genotypes as well as the C allele of IL-17F rs763780 (P = 0.0038, P = 0.0055 and P = 0.0277, respectively). The study identifies a significant association between IL-17F rs763780 polymorphisms and a higher risk of HCC in Egyptian patients with chronic hepatitis C. No significant correlation was found between the IL-17A rs2275913 polymorphism and either chronic hepatitis C or HCC.

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.

Investigating the Role of IL-17A gene rs2275913 Variant in Rosacea: In Silico Analysis Suggests Further Studies

Interleukine-17 (IL-17), a crucial component of the body's immune response against pathogens, is also implicated in various inflammatory processes. Notably, the skin of rosacea patients exhibits chronic inflammation, and IL-17 is known to induce the production of additional pro-inflammatory chemokines and cytokines. This inflammatory cascade can contribute to the hallmark features of rosacea, including dilated blood vessels, immune cell infiltration, and the development of papules and pustules. The study aimed to examine whether a specific genetic variation in the IL-17A gene (-197 G&gt;A; rs2275913) is associated with rosacea susceptibility. We compared the IL-17A variant and rosacea risk in 31 healthy individuals and 25 with rosacea. Genotyping of the IL-17A variant was performed using the PCR-RFLP method. Genotype and allele frequency distributions were compared across groups using the chi-square test (χ2). Additionally, gene ontology (GO) analysis of the IL-17A gene using web-based tools is also demonstrated. No significant association between the rs2275913 polymorphism and rosacea susceptibility was observed in this study (p=0.124) but in silico analysis suggested that the IL-17A gene interaction network might play a role in the disease. Given its critical function in regulating IL-17A and related genes, particularly in immune defense and inflammatory processes, further investigation into its potential influence on rosacea development is required.

Genetic predisposition meets cytokine imbalance: the influence of TNF-α (-308) polymorphism and TGF-β levels in pediatric acute lymphoblastic leukemia in Egypt

Evading apoptosis fuels the aggressive nature of acute lymphoblastic leukemia (ALL). This study explored the potential roles of TNF-α, a pro-apoptotic cytokine, and TGF-β, a pro-proliferative factor, in the risk of developing ALL in Egyptian children. We investigated the TNF-α rs1800629 polymorphism and serum TGF-β levels in 100 ALL patients and 100 healthy controls. Notably, specific variations in TNF-α (GA, AA genotypes, and dominant model) were associated with an increased risk of ALL, suggesting impaired apoptosis. Conversely, ALL patients exhibited significantly lower TGF-β levels, potentially promoting uncontrolled proliferation. Our findings suggest that lower TGF-β and the TNF-α (-308) dominant model are associated with an increased risk of ALL. Additionally, TGF-β demonstrated exceptional accuracy (AUC 0.995) as a potential marker, with 100% sensitivity and 96% specificity. These findings suggest that TNF-α and TGF-β may be associated with ALL susceptibility, though further research with larger and more diverse populations is necessary to confirm these results.

Long-term prognosis of adverse cardiovascular events in patients with chronic heart failure depending on the rs1143634 polymorphism of the interleukin-1β gene

The course and prognosis of chronic heart failure (CHF) are associated with the activation of inflammatory cascades, the severity of which is genetically determined.Aim: To analyze adverse cardiovascular events in patients with chronic heart failure over 5 years depending on the rs1143634 polymorphism of the interleukin-1β gene.Material and Methods. Clinical signs were studied, genotyping was carried out at the polymorphic locus rs1143634 of the IL-1β gene in patients with CHF of ischemic origin (n = 445, average age 66.4 ± 10.4 years). Information on patient outcomes over 5 years was obtained by telephone interview with endpoints: all-cause death, cardiovascular death, fatal and non-fatal cardiovascular events formed a composite endpoint. Time to event was analyzed using the Kaplan-Meier method; hazard ratio – Cox regression. Statistical processing was carried out in the Jamovi, R 4.3.1 programs.Results and conclusions. The occurrence of genotypes of the rs1143634 polymorphism of the IL-1β gene in patients with CHF and the genetic control group did not differ and was commensurate with the theoretically expected Hardy–Weinberg equilibrium. Carriers of the TT genotype were characterized by a high level of inflammation and the development of myocardial infarction at a young age. In patients with CHF of the TT genotype, the risk of death from all causes is 2.85 times higher, achieving the combined endpoint is 3.3 times higher, fatal cerebral stroke is 17.1 times higher compared to CC, 14.9 times higher than compared to ST genotype. In patients with CHF and chronic kidney disease of the TT genotype, the risk of death from cerebral stroke is 29.33 times higher than the CC genotype, and 29.12 times higher for the CT genotype. In patients with CHF in combination with diabetes mellitus, the frequency of hospitalizations due to cardiac decompensation in the TT genotype is higher than in the CC and CT genotypes (χ2 = 6.33, p = 0.042).chronic heart failure; rs1143634 polymorphism of the IL-1β gene; prognosis; cardiovascular complications

Correlation between rs7041 and rs4588 polymorphisms in vitamin D binding protein gene and COVID-19-related severity and mortality

BackgroundThe vitamin D binding protein (DBP) plays a critical role in both innate and adaptive immune systems, participating in several clinical conditions, including coronavirus disease 2019 infection severity, and mortality rate. The study aimed to investigate the correlation between rs7041 and rs4588 polymorphisms in the DBP gene and Coronavirus Disease-2019 (COVID-19) severity and mortality, in patients of Suez Canal University Hospitals in Ismailia, Egypt.MethodsA case-control study enrolled 220 individuals; 140 COVID-19 patients and 80 healthy controls. Serum 25(OH) vitamin D levels were determined by the enzyme-linked immunosorbent assay (ELISA), and rs7041 and rs4588 polymorphisms of the DBP gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThe study found that both groups had vitamin D deficiency, which was considerably lower in the COVID-19 patients group compared to controls. Among COVID-19 patients, there was a significant difference in vitamin D levels according to the disease severity indicating that vitamin D levels can be used as predictors of COVID-19 severity. Negative significant correlations between genetic variants rs4588 CA genotype and genetic variants rs7041 TT genotype and COVID-19 prevalence (p = 0.006 and 0.009 respectively) were proved. No significant correlations between all the genetic variants of both rs4588 and rs7041 and COVID-19 severity (p > 0.05). Positive significant correlations between both genetic variants rs4588 CA genotype and genetic variants rs7041 TG genotype and COVID-19 mortality (p = 0.029 and 0.031 respectively).Conclusionvitamin D deficiency increased the severity of COVID-19. The DBP polymorphism correlated with vitamin COVID-19 prevalence and mortality.

Higher relapse and worse overall survival in recipients with CTLA-4 AA genotype of rs231775 following single-unit cord blood transplantation in adults

We retrospectively investigated the impact of CTLA-4 polymorphism on outcomes for adult patients who received single-unit cord blood transplantation (CBT) at our institution. CTLA-4 genotyping was performed using real-time polymerase chain reaction with the TaqMan® SNP genotyping assay for rs231775. This study included 143 recipient–donor pairs. The multivariate analysis showed that recipient rs231775 AA was associated with worse overall survival (OS) (hazard ratio [HR], 2.92; p = 0.008) and a higher relapse rate (HR, 4.79; p = 0.002), but donor rs231775 was not. The rs231775 polymorphism in recipients and donors did not affect non-relapse mortality, hematopoietic recovery, or acute and chronic graft-versus-host disease. The beneficial effects of rs231775 GG+GA recipients on OS and relapse were notable in subgroups of patients with high-risk disease status and those with myeloid diseases. The polymorphism of CTLA-4 rs231775in recipients might be associated with the clinical outcomes of single-unit CBT.

Bone Fracture Incidence in Postmenopausal Women: Results of a 10 Year Follow Up in a RAC-OST-POL Study of rs1544410, rs7975232 and rs731236 Polymorphisms.

The clinical significance of the genetic influence of vitamin D receptor polymorphisms has still not been well-analyzed. To verify whether rs1544410, rs7975232 and rs731236 polymorphisms are associated with a higher 10-year fracture risk in postmenopausal women. The study group was a subset of a pre-defined population as part of the broader epidemiological research called the RAC-OST-POL Study and consisted of 358 postmenopausal women, chosen randomly from Racibórz (Poland) inhabitants (mean baseline age 65 ± 6.9 years, BMI 31.2 ± 5.5 kg/m2). From all participants' medical history, data concerning co-morbidities, fracture history, the medication used, parental history of bone fractures, cigarettes and alcohol use were taken at baseline. Moreover, rs1544410, rs7975232 and rs731236 polymorphisms were analyzed. Next, over the following 10 years, participants were contacted once a year and questioned concerning new fractures events and their circumstances. We did not find statistically significant main effects on the fracture incidence of single-polymorphism variants. However, there were some significant findings dependent on the co-existence of these polymorphisms and medical factors. Women with a positive history of parental fracture and configuration of CC rs7975232, AA rs731236 and CC rs1544410 had a higher fracture incidence. The risk of bone fracture was also significantly higher in the group of heterozygotes of AC rs7975232 if their BMI value was in the categories of normal weight or overweight, or if they were treated with calcium or vitamin D. Polymorphisms of rs1544410, rs7975232 and rs731236 are connected with the fracture incidence in postmenopausal women. Nevertheless, its influence should be considered with co-existing clinical factors, especially paternal fracture history, prior fracture, BMI value, any osteoporotic treatment or calcium/vit. D supplementation.

Impact of IL-6 rs1800795 and rs1800796 polymorphisms on clinical outcomes of COVID-19: a study on severity of disease in Turkish population.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is exacerbated by cytokine storms, leading to severe inflammation. Interleukin-6 (IL-6) plays a critical role in this process, and variations in its promoter may influence disease severity. This study aims to investigate the relationship between IL6 promoter polymorphisms rs1800795 (G > C) and rs1800796 (G > C) and the severity of COVID-19 in the Turkish population. A total of 332 participants were included: 84 control, 80 with mild COVID-19, and 168 with severe COVID-19. IL6 polymorphisms were genotyped using the restriction fragment length polymorphism (RFLP) method. The genotypes rs1800795 GC (OR = 3.00, 95% CI: 1.669-5.398, p < 0.000), CC (OR = 7.44, 95% CI: 2.899-19.131, p < 0.000), and rs1800796 GC (OR = 2.76, 95% CI: 1.603-4.761, p < 0.000), as well as the alleles rs1800795 C (OR = 3.01, p < 0.000) and rs1800796 C (OR = 1.97, p = 0.002), may be associated with the severity of COVID-19. According to the Jonckheere-Terpstra (J-T) test, the most significant trends that vary linearly with disease severity were observed for D-dimer [J-T = 15.896, Effect size = 0.68 (0.61 to 0.76), p < 0.000] and CRP [J-T = 15.389, Effect size = 0.66 (0.59 to 0.73), p < 0.000]. The distribution of clinical parameters across genotype combinations (rs1800796/rs1800795*) showed that GC/GC* and GC/CC* were linked to a higher risk of severe inflammation, clotting, and organ damage. Additionally, it has been determined that the G-C and C-C haplotypes may be associated with increased severity of COVID-19. The rs1800795 and rs1800796 polymorphisms are linked to COVID-19 severity and could help guide future treatment strategies.

The association of the rs4588 and rs7041 polymorphisms of the VDBP gene and vitamin D status in obese individuals

BACKGROUND: Vitamin D (VD) plays an important role in bone metabolism, regulating phosphorus and calcium in the body. The VD binding protein (VDBP) binds to VD metabolites and transports them to the target tissues; it is assumed that polymorphisms of this gene influence the absorption of VD in the body. However, the relationship between polymorphisms of the VDBP gene and blood VD levels in obesity has not yet been sufficiently investigated. AIM: To identify the relationship of blood VD content (form 25(OH)D3) of obese and non-obese persons and the VDBP gene polymorphisms rs4588 and rs7041. METHODS: 80 residents of the Kaliningrad region participated in the study. The participants were divided according to VD status (norm, insuffient, deficiency and severe deficiency) and body mass index (BMI). Blood VD levels were determined using an ELISA. Genomic DNA was isolated from whole blood. Restriction analysis was performed with the endonucleases HaeIII and ErhI to determine the VDBP gene polymorphisms. RESULTS: There were no significant differences in blood VD levels of obese and non-obese individuals. Within the genotypes of the rs4588 polymorphism (CA), VD levels did not differ in individuals with different BMI (CС p=0.186; CA p=0.350, AA data is insufficient). However, when analyzing the allele frequencies in groups with different VD status, a significant difference was found in all groups compared to the control (insufficient p=0.009; deficiency p=0.010; severe deficiency p0.001). When analyzing the rs7041 polymorphism of the VDBP gene (TG), splitting groups by BMI within specific genotypes did not reveal differences in VD levels (TG p=0.150; GG p=0.087; TT data is insufficient), but we found a significant difference between control and severe deficiency (p0.001) based on allele frequencies of the rs7041 polymorphism. CONCLUSION: The VD content in blood of the obese individuals was comparable to that of the control group. The presence of the VDBP gene rs7041 and rs4588 polymorphisms has no influence on blood VD level, regardless of BMI. However, allele A of the rs4588 polymorphism is associated with an unfavorable VD status, while allele G of the rs7041 polymorphism is associated with normal blood VD levels.

Impact of gene polymorphisms involved in the vitamin D metabolic pathway on the susceptibility to and severity of autism spectrum disorder

This study explores the association between genetic variations in the vitamin D pathway and autism spectrum disorder (ASD) susceptibility and severity in Thai children. A total of 276 participants, including 169 children with ASD and 107 healthy controls, were recruited. Genotyping of vitamin D pathway genes (CYP2R1, CYP27B1, GC, and VDR) was conducted using TaqMan-based real-time PCR, while serum vitamin D levels were measured by chemiluminescence immunoassay. ASD severity was assessed via the Childhood Autism Rating Scale, 2nd Edition. Results reveal that the VDR gene (ApaI) rs7975232 is linked to a reduced ASD risk. In contrast, the GC gene rs7041 (A > C) polymorphism shows a significant association with increased ASD risk and severity, particularly in individuals with both the GC gene polymorphism and vitamin D insufficiency. Additionally, there was a higher prevalence of the GC1s isoform and GC1s-GC1s haplotype in children with ASD, associated with ASD severity. This study identified that individuals possessing GC rs7041 C alleles and the GC1s genotype (rs7041C/rs4588G) exhibit an increased susceptibility to and more severity of ASD. Further studies with larger cohorts are essential to fully understand these genetic polymorphisms’ roles.

A Meta-Analysis of Association Between Interleukin Polymorphisms (rs4073, rs1800925, rs1179251, rs1179246, rs2227485, rs17855750, and rs153109) and Colorectal Cancer Risk.

Interleukins (ILs) play a significant role in triggering the inflammatory response in blood vessels and immune cells. A systematic review and meta-analysis were conducted to investigate the relationship between IL-8 (rs4073), IL-13 (rs1800925), IL-22 (rs1179251, rs1179246, and rs2227485), and IL-27 (rs17855750 and rs153109) polymorphisms and the risk of developing colorectal cancer (CRC). Four databases were searched up until October 13, 2023, without any restrictions, to find relevant studies. The association was evaluated using crude odds ratios (ORs) and 95% confidence intervals in five genetic models. A total of twenty-three articles were entered into the meta-analysis. The pooled ORs (p-values) for the IL-8 (rs4073) polymorphism were 0.98 (0.63), 0.93 (0.44), 0.89 (0.13), 0.94 (0.38), and 0.99 (0.90) for studies following HWE without heterogeneity, and for all studies with high heterogeneity were 1.03 (0.69), 1.30 (0.07), 1.04 (0.71), 1.12 (0.20), and 1.23 (0.06). For the IL-13 (rs1800925) polymorphism, the pooled ORs were 1.44 (0.06), 2.58 (0.0004), 1.72 (0.16), 1.82 (0.09), and 2.37 (0.001) in AHHDR models, respectively. The pooled ORs of IL-22 (rs1179251) polymorphism for AHHDR models were 0.97 (0.92), 0.92 (0.90), 0.98 (p = 0.95), 1.08 (0.87), and 0.96 (0.82), respectively. The pooled ORs of IL-22 (rs1179246) polymorphism for AHHDR models were 0.98 (0.67), 0.97 (0.80), 0.92 (0.36), 0.93 (0.42), and 1.02 (0.84), respectively. The pooled ORs of IL-22 (rs2227485) polymorphism for AHHDR models were 1.47 (0.02), 2.03 (0.02), 1.28 (0.29), 1.52 (0.06), and 1.70 (0.04), respectively. The pooled ORs of IL-27 (rs17855750) polymorphism for AHHDR models were 0.53 (0.46), 0.19 (0.28), 1.10 (0.60), 0.55 (0.58), and 0.27 (p = 0.05), respectively. The pooled ORs of IL-27 (rs153109) polymorphism for AHHDR models were 1.28 (0.007), 1.45 (0.002), 1.40 (0.0002), 1.41 (< 0.0001), and 1.20 (0.09), respectively. The results reported that just the TT genotype of IL-13 (rs1800925), the T allele and TT genotype of IL-22 (rs2227485), and the G allele and GG, AG and GG + AG genotypes of IL-27 (rs153109) polymorphisms had an elevated risk in CRC patients.

The effect of the TNFα gene rs1800629 polymorphism on cytokine profile parameters in the complicated wound healing in combat trauma victims

Background. In the wound process, there is a high probability of complications in the form paratraumatic eczema (РТЕ), which determines the severity the course of wound repair. Genetic factors responsible for the regulation of cytokines a leading role in the etiopathogenesis of РТЕ. Aim — determine the relationship of TNFa gene rs1800629 with the development of РТЕ and IL-1ß, TNFα, IL-6. Materials and methods. The study included 162 patients after surgical interventions. Group I — 82 people with complications in the form PTE and II — 80 people without complications. The study rs1800629 TNFα gene was carried out by the poly- merase chain reaction method. The levels TNFα, IL-1β and IL-6 in the blood was determined by the enzyme immunoassay method. Results. A connection with PTE was established with of rs1800629 gene TNFα (p = 0.033 and p = 0.005). The genotypes GA (OR = 1.64; CI 0.83–3.24) and AA (OR = 2.94; CI 0.9–9.67), allele A (OR = 2.13; CI 1.26–3.6) rs1800629 influenced the increased chances of developing PTE. In group II the IL- 1β, TNFα, IL-6 indicators were increased (p &lt; 0.001) in carriers of the AA genotype rs1800629. Conclusion. rs1800629 TNFα gene is associated with development of PTE. An increase in the levels IL-1β, TNFα, IL-6 was associated with the presence of a pathogenetic factor — AA genotype rs1800629 TNFα gene in development of complications.