Rs1800629 Polymorphism Research Articles

Interleukin-1β rs1143634 Polymorphism and Susceptibility to Periodontitis in the Iraqi Population.

Periodontitis is a complex multifactorial inflammatory disease, and its genetic basis has been studied. The Interleukin-1 beta (IL-1β) is a crucial proinflammatory mediator in the pathogenesis of periodontitis with high polymorphism. This study aimed to investigate whether the rs1143634 genetic variant of the IL-1β gene is associated with an increased risk for periodontitis. For this purpose, genotyping of the IL-1β rs1143634 polymorphism was performed using the polymerase chain reaction-restriction fragment length polymorphism method on 90 patients within the age range of 35-60 years old. They were divided into two groups: 64 periodontitis cases (stage 3 and 4 periodontitis according to 2017 classification) and 26 racially matched healthy cases as the control group. Fisher's exact test showed a significant decrease in TT homozygous genotype in periodontitis cases, compared to the control group (P=0.018), suggesting that this genotype is a protective factor in the test population. Allele frequency showed an elevated odd ratio (1.24) and increased risk for periodontitis in subjects with allele C and reduced odd ratio (0.81) and reduced risk for periodontitis in subjects with allele T. Allele T of IL-1β rs1143634 polymorphism could be a protective factor, while Allele C of this polymorphism could be a risk factor for periodontitis in the studied Iraqi population.

Role of FokI rs2228570 and Tru9I rs757343 Polymorphisms in the Mortality of Patients Infected with Different Variants of SARS-CoV-2

Low vitamin D levels are associated with the severity of coronavirus disease 19 (COVID-19). Vitamin D receptor gene polymorphisms, such as Tru9I rs757343 and FokI rs2228570, have been suggested to be potential risk factors for severe COVID-19 outcomes. This study investigated how Tru9I rs757343 and FokI rs2228570 polymorphisms influenced the mortality rate of COVID-19 in relation to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. The polymerase chain reaction-restriction fragment length polymorphism assay was used to genotype Tru9I rs757343 and FokI rs2228570 genotypes in 1,734 recovered and 1,450 deceased patients. Our results demonstrated that the high mortality rate was correlated with FokI rs2228570 TT genotype in all three variants but was much higher in the Omicron BA.5 variant than in the Alpha and Delta variants. Furthermore, in patients infected with the Delta variant, FokI rs2228570 CT genotype was more highly correlated with the mortality rate compared to other variants. Thus, a high mortality rate was correlated with the Tru9I rs757343 AA genotype in the Omicron BA.5 variant, whereas this relationship was not observed in the other two variants. The T-A haplotype was related to COVID-19 mortality in all three variants, but its effect was more pronounced in the Alpha variant. Moreover, the T-G haplotype was significantly associated with all three variants. Our findings showed that the effects of Tru9I rs757343 and FokI rs2228570 polymorphisms were related to SARS-CoV-2 variants. However, further studies are still required to validate our findings.

Influence of IL-6 rs1800795 and IL-8 rs2227306 polymorphisms on COVID-19 outcome.

Severe coronavirus disease 2019 (COVID-19) is mainly precipitated by an uncontrolled inflammatory response and cytokine storm. Pro-inflammatory cytokines such as IL-6 and IL-8 levels were markedly increased in complicated cases. Genetic polymorphisms may have a role in this dysregulated expression during SARS-CoV-2 infection. Our aim was to assess the influence of IL-6 and IL-8 single nucleotide polymorphisms (SNPs) on COVID-19 outcomes. 240 subjects were involved in the study; 80 cases with severe COVID-19, 80 cases with mild COVID-19, and 80 healthy subjects. IL-6rs1800795(G/C) and IL-8 rs2227306(C/T) genotyping was performed using real-time polymerase chain reaction (PCR). Ages ranged between 20-67 years in all groups. There was a statistically significant association between the male gender and severe COVID-19. A significantly higher expression of IL-6rs1800795GG and IL-8rs2227306CC genotypes was observed among patients with severe COVID-19 than other groups. At the allele level, IL-6rs1800795G and IL-8rs2227306C alleles were more frequent among patients with severe COVID-19 when compared with other groups. Haplotypes' frequency clarified that the coexistence of IL-6 rs1800795G and IL-8rs2227306C alleles in the same person increased the risk of severe COVID-19 outcomes. Carriers of IL-6rs1800795C and IL-8 rs2227306T alleles are at lower risk of developing severe COVID-19. Multivariate logistic regression analysis showed that old age, male gender, IL-6 rs1800795CG+GG, and IL-8 rs2227306CT+CC genotypes could be independent risk factors for severe COVID-19 outcomes. IL-6 rs1800795G and IL-8 rs2227306C alleles are significantly associated with severe COVID-19 outcomes, especially if they coexist. They may be used as prognostic markers for COVID-19.

Serum vitamin D levels and vitamin D receptor gene ApaI and TaqI polymorphisms in patients with morphea: a case-control study.

A uncommon inflammatory condition called morphea causes fibrosis in the skin and subcutaneous tissue. The key stages in the pathophysiology are vascular damage, immunological response, and fibrosis. Numerous research have examined the relationships between the immune system, fibrosis, and vitamin D, but the exact pathogenetic pathways of morphea remain poorly understood. The purpose of this study was to investigate serum 25(OH)D levels and the ApaI (rs7975232) and TaqI (rs731236) polymorphisms of the vitamin D receptor (VDR) in morphea patients. There were 48 age- and sex-matched controls and 41 morphea patients total. VDR polymorphisms were found using PCR tests and gel electrophoresis, and serum 25(OH)D levels were determined using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). The patient group consisted of 37 females (90.2%) and 4 males (9.8%). The patients' mean age was 38.68 ± 17.54years. In terms of VDR ApaI and TaqI polymorphisms, there was no discernible difference between the patient and control groups. TaqI polymorphism heterozygosity was discovered in all patients with progressive disease, and this finding was statistically significant (p = 0.012). Patients' mean serum 25(OH)D levels were 16.98 ± 11.55ng/mL, while those in the control group were 18.02 ± 14.30ng/mL. VDR polymorphisms, vitamin D levels, disease subtype, age of onset, and responsiveness to treatment did not significantly correlate. In our research, we discovered that TaqI polymorphism may be related to the severity of the disease and that the polymorphisms of the VDR ApaI and TaqI were not associated with morphea susceptibility.

Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway and Their Relationship with High Blood Pressure Risk.

High blood pressure (HBP) is the leading risk factor for cardiovascular disease (CVD) and all-cause mortality worldwide. The progression of the disease leads to structural and/or functional alterations in various organs and increases cardiovascular risk. Currently, there are significant deficiencies in its diagnosis, treatment, and control. Vitamin D is characterized by its functional versatility and its involvement in countless physiological processes. This has led to the association of vitamin D with many chronic diseases, including HBP and CVD, due to its involvement in the regulation of the renin-angiotensin-aldosterone system. The aim of this study was to evaluate the effect of 13 single nucleotide polymorphisms (SNPs) related to the vitamin D metabolic pathway on the risk of developing HBP. An observational case-control study was performed, including 250 patients diagnosed with HBP and 500 controls from the south of Spain (Caucasians). Genetic polymorphisms in CYP27B1 (rs4646536, rs3782130, rs703842, and rs10877012), CYP2R1 rs10741657, GC rs7041, CYP24A1 (rs6068816, and rs4809957), and VDR (BsmI, Cdx2, FokI, ApaI, and TaqI) were analyzed by real-time PCR using TaqMan probes. Logistic regression analysis, adjusted for body mass index (BMI), dyslipidemia, and diabetes, showed that in the genotypic model, carriers of the GC rs7041 TT genotype were associated with a lower risk of developing HBP than the GG genotype (odds ratio (OR) = 0.44, 95% confidence interval (CI): 0.41-0.77, p = 0.005, TT vs. GG). In the dominant model, this association was maintained; carriers of the T allele showed a lower risk of developing HBP than carriers of the GG genotype (OR = 0.69, 95% CI: 0.47-1.03; TT + TG vs. GG, p = 0.010). Finally, in the additive model, consistent with previous models, the T allele was associated with a lower risk of developing HBP than the G allele (OR = 0.65, 95% CI: 0.40-0.87, p = 0.003, T vs. G). Haplotype analysis revealed that GACATG haplotypes for SNPs rs1544410, rs7975232, rs731236, rs4646536, rs703842, and rs10877012 were associated with a marginally significant lower risk of developing HBP (OR = 0.35, 95% CI: 0.12-1.02, p = 0.054). Several studies suggest that GC 7041 is associated with a lower active isoform of the vitamin D binding protein. In conclusion, the rs7041 polymorphism located in the GC gene was significantly associated with a lower risk of developing HBP. This polymorphism could therefore act as a substantial predictive biomarker of the disease.

Association between interleukin-10 gene polymorphisms (rs1800871, rs1800872, and rs1800896) and severity of infection in different SARS-CoV-2 variants

BackgroundPolymorphisms in the interleukin-10 (IL10) gene have been linked to the severity of the patients infected with the viral infections. This study aimed to assess if the IL10 gene polymorphisms rs1800871, rs1800872, and rs1800896 were linked to coronavirus disease 19 (COVID-19) mortality in different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the Iranian population.MethodsFor genotyping IL10 rs1800871, rs1800872, and rs1800896, this study used the polymerase chain reaction-restriction fragment length polymorphism method in 1,734 recovered and 1,450 deceased patients.ResultsThe obtained finding indicated IL10 rs1800871 CC genotype in the Alpha variant and CT genotype in the Delta variant had a relationship with COVID-19 mortality; however, there was no association between rs1800871 polymorphism and the Omicron BA.5 variant. The COVID-19 mortality rate was associated with IL10 rs1800872 TT genotype in the Alpha and Omicron BA.5 variants and GT in the Alpha and Delta variants. The COVID-19 mortality rate was associated with IL10 rs1800896 GG and AG genotypes in the Delta and Omicron BA.5; nevertheless, there was no association between rs1800896 polymorphism with the Alpha variant. According to the obtained data, the GTA haplotype was the most common of haplotype in different SARS-CoV-2 variants. The TCG haplotype was related to COVID-19 mortality in the Alpha, Delta and Omicron BA.5 variants.ConclusionThe IL10 polymorphisms had an impact on COVID-19 infection, and these polymorphisms had different effects in various SARS-CoV-2 variants. To verify the obtained results, further studies should be conducted on various ethnic groups.

Association between IL-6 rs1800795 and IL-1β rs 16944 gene polymorphisms with clinical severity of COVID-19 patients in Surakarta, Central Java, Indonesia

Background: Cytokine plays a pivotal role in the pathogenesis of coronavirus disease 2019 (COVID-19). Cytokine storm is characterized by rapid elevation of an inflammatory circulating cytokine such as interleukin-6 (IL-6) and IL-1. However, according to evidence, genetic variables may affect the development and course of infectious diseases. Multiple genetic polymorphisms, mostly single-nucleotide polymorphisms (SNPs), have been linked to this setting's predisposition to viral infections. This study aimed to determine the frequency distribution of IL-6 SNPs rs1800795 and IL-1β SNPs rs16944 and rs1143627 gene polymorphisms and their association with the clinical severity of COVID-19 patients in Surakarta, Indonesia. This study aims to determine the association between IL-6 rs1800795 and IL-1β rs16944 with COVID-19 clinical severity. Methods: This study used a cross sectional design conducted at Universitas Sebelas Maret Hospital and centralized isolation of the Donohudan Hajj Dormitory from May to November 2021. A total of 120 COVID-19 patients were divided into 3 groups: asymptomatic, mild-moderate, and severe-critical. The detection of IL-6 SNPs rs1800795 and IL-1β SNPs rs16944 was carried out by quantitative PCR (qPCR) examination, and IL-6 and IL-1β were determined by the ELISA method. Result: There was no significant association between IL-6 SNPs rs1800795 (p=1.000) and IL-1β SNPs rs16944 (p=0.119) with clinical severity. In IL-1β SNPs rs16944 gene polymorphisms, the GG genotype was more commonly found in the asymptomatic group. AG genotype was commonly found in the symptomatic group (mild to critical). There was a significant association between IL-1β levels and clinical severity (p=0.03), whereas the association between IL-6 levels and clinical severity is not significant (p=0.103). Conclusion: There was a correlation between IL-1β levels with clinical severity. In IL-1β SNPs rs16944, the GG genotype may act as a protective factor, whereas the AG genotype may act as a factor that increases the clinical severity of COVID-19.

Association of ApaI rs7975232 and BsmI rs1544410 in clinical outcomes of COVID-19 patients according to different SARS-CoV-2 variants

A growing body of research has shown how important vitamin D is in the prognosis of coronavirus disease 19 (COVID-19). The vitamin D receptor is necessary for vitamin D to perform its effects, and its polymorphisms can help in this regard. Therefore, we aimed to evaluate whether the association of ApaI rs7975232 and BsmI rs1544410 polymorphisms in different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were influential in the outcomes of COVID-19. The polymerase chain reaction-restriction fragment length polymorphism method was utilized to determine the different genotypes of ApaI rs7975232 and BsmI rs1544410 in 1734 and 1450 patients who had recovered and deceased, respectively. Our finding revealed that the ApaI rs7975232 AA genotype in the Delta and Omicron BA.5 and the CA genotype in the Delta and Alpha variants were associated with higher mortality rate. Also, the BsmI rs1544410 GG genotype in the Delta and Omicron BA.5 and the GA genotype in the Delta and Alpha variants were related to a higher mortality rate. The A-G haplotype was linked with COVID-19 mortality in both the Alpha and Delta variants. The A-A haplotype for the Omicron BA.5 variants was statistically significant. In conclusion, our research revealed a connection between SARS-CoV-2 variants and the impacts of ApaI rs7975232 and BsmI rs1544410 polymorphisms. However, more research is still needed to substantiate our findings.

Single Nucleotide Polymorphisms in IL-1A RS1800587, IL-1B RS1143634 and Vitamin D Receptor Rs731236 in Stage III Grade B/C Periodontitis.

The purpose of the study is to determine the prevalence of interleukin (IL)-1A (rs1800587), IL-1B (rs1143634) and vitamin D receptor (VDR) (TaqI, rs731236) gene polymorphisms in the Turkish population and their association with Stage III Grade B/C periodontitis. Systemically and periodontally healthy individuals (N = 100) and Stage III Grade B/C periodontitis patients (N=100) based on clinical and radiographic examination were included in this research. Clinical attachment level, probing depth, bleeding on probing, plaque and gingival indices of the subjects were measured. Genotyping of IL-1A (rs1800587), IL-1B (rs1143634) and VDR (rs731236) polymorphisms was conducted by Real Time PCR. Allelic and genotypic distributions of IL-1A (rs1800587) gene polymorphism were not associated with periodontitis (p>0.05). In IL-1B (rs1143634) gene polymorphism, the C allele was detected more frequently in healthy individuals compared with the periodontitis patients (p=0.045). CC genotype and C allele in VDR (rs731236) gene polymorphism was higher in periodontitis patients (p=0.031, p=0.034, respectively). In comparison with Grade B periodontitis patients and healthy subjects, CC genotype and C allele were observed more frequently in the Grade B periodontitis in terms of alleles (C/T) and genotypes for VDR (rs731236) polymorphism (p=0.024, p=0.008, respectively). This study presents that the VDR (rs731236) polymorphism are associated with enhanced susceptibility to Stage III periodontitis in the Turkish population. Furthermore, VDR (rs731236) polymorphism may be used as an identification criteria to discriminate Grade B and Grade C in Stage III periodontitis.

A preliminary study on the association between pro-inflammatory cytokine IL-1 beta polymorphisms and susceptibility to hepatitis C infection in Malay male Malay drug abusers

Introduction: Hepatitis C virus (HCV) infection frequently leads to liver complications, such as fibrosis, cirrhosis, and hepatocellular carcinoma. The incidence of HCV infection transmission among drug abusers is concerning. Interleukin-1 beta (IL-1b) is a pro-inflammatory cytokine secreted during innate and adaptive immune responses and plays a pivotal role in chronic inflammatory diseases. Functional single nucleotide polymorphisms in IL-1b cause it to play different roles in disease susceptibility and progression. This study aimed to investigate the association between genetic polymorphisms of pro-inflammatory cytokines (IL-1b) and HCV infection susceptibility in Malay male drug abusers. Methods: In total, 48 male Malay drug abusers were included in this retrospective case-control study. Genomic DNA was extracted from whole blood samples and analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the IL-1b rs16944 and rs1143634 polymorphisms. Results: Analysis of IL-1b rs1143634 revealed that the C/C genotype was common in both the case and control groups; however, no statistical significance was observed (p = 0.068, c2 = 3.755). Genotyping of IL-1b demonstrated that all samples were of the homozygous mutant type (T/T). Conclusion: There was no association between IL-1b polymorphism (rs1143634 and rs16944) and hepatitis C infection susceptibility among Malay male drug abusers.

Оцінка ризику розвитку соматотропної недостатності залежно від розподілу частот алелей і генотипів поліморфного локусу rs1544410 BsmI гена рецептора вітаміну D

Growth hormone deficiency (GHD) is a disease caused by a significant disturbance in the growth hormone (GH) /growth factor system, it occures as a result of various hereditary or acquired causes and is characterized, first of all, by a significant delay in the child's growth and physical development. GHD can be isolated or combined with deficiency of other adenohypophysis hormones. The presence of a relationship between the GH /growth factor system and vitamin D (vit D) determines the involvement of genetic changes in the vit D receptor (VDR) in the pathogenesis of GHD. Purpose - to assess the risk of developing GHD based on the investigation of the distribution of allele frequencies and genotypes of the polymorphic locus rs1544410 BsmI of the VDR gene. Materials and methods. The determination of VDR BsmI gene (rs1544410) polymorphism was performed using the polymerase chain reaction method, followed by analysis of the length of restriction fragments upon their detection by agarose gel electrophoresis in 22 prepubertal children with GHD. The serum 25-hydroxycalciferol (25(OH)D) level was determined by immunochemiluminescent method on microparticles (Abbott, USA). Results. G/A allele was most often found in children with isolated GHD and multiple pituitary insufficiency (MPH) (43.8% and 83.3%, respectively). In the presence of G/A and G/G genotypes, the risk of GHD is reliably high: OR=3.60 (95% CI 1.40-9.23); OR=10.69 (95% CI 2.34-48.85) respectively; with the A/A genotype variant the risk of GHD is reliably low OR=0.11 (95% CI 0.04-0.33). Carrying the G allele of the polymorphic locus rs1544410 Bsm I of the VDR gene is associated with the risk of developing GHD OR=5.58 (95% CI 4.51-6.90; p<0.001). A significantly difference in the peak GH release was established in patients carrying the G/G and A/A, G/G and G/A alleles. 83.33% of children with MPH and 68.49% with isolated GHD had hypovitaminosis D. Vit D deficiency was recorded in carriers of all three types of alleles. Conclusions. In the presence of G/A and G/G genotypes, the risk of GHD increases, in the presence of the A/A genotype, it decreases. The G allele carrier of the polymorphic locus rs1544410 Bsm I of the VDR gene is associated with the risk of developing GHD OR=5.58 (95% CI 4.51-6.90; p<0.001), despite the ideal distribution of genotypes. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Evaluation of the Association of VDR rs2228570 Polymorphism with Elite Track and Field Athletes' Competitive Performance.

The present study aimed to examine the vitamin D receptor (VDR), rs2228570 polymorphism, and its effect on elite athletes' performance. A total of 60 elite athletes (31 sprint/power and 29 endurance) and 20 control/ physically inactive, aged 18-35, voluntarily participated in the study. The International Association of Athletics Federations (IAAF) score scale was used to determine the performance levels of the athletes' personal best (PB). Whole exome sequencing (WES) was performed by the genomic DNA isolated from the peripheral blood of the participants. Sports type, sex, and competitive performance were chosen as the parameters to compare within and between the groups by linear regression models. The results showed no statistically significant difference between the CC, TC, and TT genotypes within and between the groups (p > 0.05). Additionally, our results underlined that there were no statistically significant differences for the association of rs2228570 polymorphism with PBs within the groups of the (p > 0.05) athletes. The genetic profile in the selected gene was similar in elite endurance, sprint athletes, and in controls, suggesting that rs2228570 polymorphism does not determine competitive performance in the analyzed athlete cohort.

The forkhead box protein P3 gene rs3761548 promoter polymorphism confers a genetic contribution to the risk of preeclampsia: A systematic review and meta-analysis

Various studies have investigated the risk of preeclampsia with the forkhead box protein P3 (FOXP3) gene rs2232365 and rs3761548 polymorphisms. However, the results remained contradictory. A comprehensive literature search was conducted using the Cochrane Library, PubMed, and Web of Science (up to Oct 11, 2021). Meta-analysis was carried out in the R language environment for statistical computing and graphics. A fixed-effect or random-effects model was used according to the statistical significance of heterogeneity among included studies. The pooled odds ratios and corresponding 95% confidence intervals were calculated to estimate the strength of the effect. For the rs2232365 polymorphism, statistical significance was detected neither in the overall population nor among the East Asian and West Asian subgroups. However, for rs3761548, the summarized statistics revealed a significant association between the C allele carriage and preeclampsia risk in the homozygote, heterozygote, and dominant models. The further stratified analysis found this effect might be specific to West-South Asian ethnic subgroups. To sum up, this meta-analysis showed that the FOXP3 rs3761548 polymorphism was significantly associated with preeclampsia susceptibility, and it had a deleterious effect especially in the West-South Asian population. In contrast, rs2232365 may serve as neither a protective nor a risk factor for preeclampsia onset.

Interleukin 12B rs3212227 and rs6887695 single nucleotide polymorphisms are associated with the susceptibility to preeclampsia: Genetic, haplotype and bioinformatics analysis

It is well-known that functional single nucleotide polymorphisms (SNPs) in IL-12B gene might intensely change the protein expression level, or modify its functions, which might result in immune disorders. The association between common IL-12B SNPs with preeclampsia (PE) risk has remained unclear yet. In a case-control study, 253 PE patients and 250 healthy subjects were genotyped for SNPs in IL-12B rs3212227 by PCR-RFLP and in IL-12B rs6887695 by AS-PCR. Novel in-silico analysis were performed to predict the potential functions of these polymorphisms, as well. The rs3212227 variation in IL12B gene showed an association with susceptibility to PE. The AC and CC genotypes and also C allele of this SNP were more frequent in patients. Likewise, they were frequent in early onset and late onset PE. The G allele and GC and CC genotype of rs6887695 SNP correlated negatively with PE development and it shown protective effect on PE risk. In addition, the AG and CC haplotypes of IL-12B were more prevalent in PE patients. Then, IL12B AC haplotype was less frequent in PE compare to healthy pregnant women. In-silico analysis of IL-12B rs3212227 gene polymorphism might not have significant impact on the mRNA structure and transcription of IL-12B. The results of our study revealed a significant relationship between rs3212227A/C and rs6887695G/C polymorphisms in IL-12B gene and the risk of PE in the Iranian population.

The 4G/5G polymorphism of plasminogen activator inhibitor type 1 is a predictor of allergic cough.

Background: It has been suggested that genetic factors may be substantially linked to allergy disorders. This study aims to investigate the relationship between the genetic susceptibility of Chinese patients with allergy disorders and the polymorphisms of plasminogen activator inhibitor 1 gene (PAI-1) rs1799762, cysteinyl leukotriene receptor 1 gene (CYSLTR1) rs320995, gasdermin B gene (GSDMB) rs7216389, glycoprotein IIIa gene (GPIIIa) rs5918, glycoprotein Ib alpha gene (GP1BA) rs6065, platelet endothelial aggregation receptor 1 gene (PEAR1) rs12041331, and tumor necrosis factor alpha gene (TNF-α) rs1800629. Methods: From the Peking Union Medical College Hospital, this study enrolled 60 healthy participants and 286 participants with allergic diseases. TaqMan-minor groove binder (MGB) quantitative polymerase chain reaction (qPCR) was used to examine the gene polymorphisms in each group. Results: The TaqMan-MGB qPCR results were completely consistent with the DNA sequencing results, according to other studies in this medical center (Kappa = 1, p < .001). Only the distribution of PAI-1 rs1799762 was different between patients with allergic cough and healthy people (χ2 = 7.48, p = .0238). With regard to cough patients, the 4G4G and 5G5G genotypes were more frequent (allergic cough vs. healthy individuals: 4G4G 57.9% vs. 26.7%; 5G5G 20.0% vs. 13.3%), but the 4G5G genotype was more frequent in healthy people (allergic cough vs. healthy individuals: 45.7% vs. 60.0%). The CYSLTR1 rs320995, GSDMB rs7216389, GPIIIa rs5918, GP1BA rs6065, PEAR1 rs12041331, and TNF-α rs1800629 polymorphisms, however, did not show any of such relationships. Conclusion: The PAI-1 rs1799762 polymorphisms may be associated with the genetic susceptibility of Chinese allergic disease patients with cough performance.

Role of the Vitamin D Receptor (VDR) in the Pathogenesis of Osteoporosis: A Genetic, Epigenetic and Molecular Pilot Study.

The vitamin D receptor (VDR) regulates bone development and calcium homeostasis, suggesting a central role in musculoskeletal diseases such as osteoporosis (OP). Several studies have examined the contribution of VDR polymorphisms and epigenetic signatures in bone metabolism and OP risk, with sometimes inconclusive results. Our study aimed to explore the association between genetic variability, expression and the methylation pattern of VDR with the risk of OP in a cohort of Caucasian patients. Genomic DNA from 139 OP, 54 osteopenic (Ope) and 73 healthy (CTR) subjects were used for genotyping the rs731236 (TaqI), rs2228570 (FokI) and rs11568820 (Cdx2) polymorphisms of the VDR gene by an allelic discrimination assay. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of VDR expression levels and pyrosequencing analysis of a VDR promoter CpG island were carried out in a subcohort (25 OP and 25 CTR) of subjects. Data obtained showed a significantly higher OP risk for rs11568820 G/A and A/A genotypes (p = 0.05). qRT-PCR revealed lower VDR gene expression levels in the OP group compared to CTR subjects (p = 0.0009), also associated with both the rs11568820 A/A genotype (p = 0.03) and femoral fragility fractures (p = 0.05). No association was found between the methylation pattern of the region analyzed of the VDR promoter and its expression levels. Our results identify a significative association between Cdx2 rs11568820 polymorphism and OP risk. In addition, the VDR transcriptomic profile suggests a putative interconnection with OP progression, providing a useful tool to stratify OP phenotype and fragility fracture risk.

Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus.

STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4 genes has a major impact on the generation of autoimmunity. However, there are few studies evaluating the impact of these variants on the production of proinflammatory cytokines such as IFN-γ and IL-17A. Methods-A case-control study was carried out with 206 Mexican mestizo patients residing in Western Mexico with a diagnosis of SLE and a group of 80 patients without autoimmune diseases was captured to determine the cut-off point for high IFN-γ levels. In this study, SLE patients with high IFN-γ levels were considered as cases (cut-off > 15.6 pg/mL), and SLE patients with normal IFN-γ levels were considered as controls (cut-off ≤ 15.6 pg/mL). Disease activity was identified from the systemic lupus erythematosus disease activity index (SLEDAI). For the determination of levels of cytokines IFN-γ, IL-12, and IL17A, commercial ELISA kits were used. Genotyping of STAT4 rs7574865 (G > T) was performed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. Results-The patients with SLE had a median age of 45 years with a range of disease duration from 4 years to 18 years; 45.6% were identified as having disease activity. In this sample, we identified a high IFN-γ prevalence of 35.4%. The levels of IFN-γ were higher in the patients with genotype TT than GG. We found that TT genotype conferred a higher risk of high IFN-γ when compared to the GG and GT genotypes. Conclusions-In this study, we identified that the polymorphic genotype TT of the STAT4 gene rs7574865 polymorphism is associated with increased levels of IFN-γ. However, its strength of association was weak, so complementary studies are needed to evaluate its impact on SLE patients.

Association between polymorphism loci rs7041, rs4588 in vitamin D-binding protein receptor gene with comorbid with mortality sepsis patients in intensive care unit General Hospital M. Djamil Padang, West Sumatra

Background: Many factors influence the disease, one of which is comorbidity. Comorbid is a condition in which a person simultaneously suffers from two or more diseases. The disease is generally chronic. Patients with comorbid diseases are more at risk of experiencing increased healthcare costs, experiencing obstacles in the healing process, and even death. Loci rs7041 and rs4588 polymorphism of VDBP receptor gene contributed to the pathogenesis of sepsis patients. According to several previous studies, Vitamin D levels and comorbidities affected the mortality of sepsis patients. Several previous studies had linked VDBP with mortality in sepsis. This study aimed to determine the relationship between the loci rs7041 and rs4588 polymorphism and comorbidities with the mortality of sepsis patients. Method: This research was a descriptive observational study with a prospective cohort design. The total data for this study were 80 samples, consisting of 40 samples of Vitamin D deficiency and 40 samples of non- deficiency Vitamin D. Data were analyzed using the Chi-Square test or the fisher test. Result: The average age of patients with vitamin D deficiency was 56 years, for females (77,5%), mean APACE II score (20), and mean SOFA score (7). Non-deficient vitamin D with an average age of 50 years, males (70,0%), mean APACE II score (18) and mean SOFA score (5). Diabetes mellitus was the highest comorbidities in rs7041 locus polymorphism (80,0%), underweight in rs4588 locus polymorphism (66,7%) and obesity for non-survival events (64,3%). There was no significant association between comorbidities and rs7041 locus polymorphism, rs4588 locus polymorphism and severity sepsis patients with pValue &gt; 0,05. Conclusion: Obesity is the highest comorbid for mortality in sepsis patients, but loci rs7041 and rs4588 polymorphisms have no relation to comorbidities.

АССОЦИАЦИИ ПОЛИМОРФИЗМА ГЕНА РЕЦЕПТОРА ВИТАМИНА D (VDR) И РЕЦЕССИИ ДЕСНЫ В СМЕННОМ ПРИКУСЕ

Subject of study. The development of new approaches to early diagnosis and identification of predisposition to the formation of gingival recession in children is an urgent task of modern dentistry. It is known that vitamin D plays an important role, affecting, among other things, the immune system and calcium-phosphorus homeostasis through the vitamin D receptor (VDR). In connection with the above, a promising direction is the study of polymorphisms of the vitamin D receptor gene to determine markers of gingival recession in a removable bite.&#x0D; Purpose: to study the relationship of the polymorphic marker Bsm I (rs1544410 T/C) of the VDR gene with a predisposition to gingival recession in children in a removable bite living in the Republic of Tatarstan.&#x0D; Methodology. We examined 81 children with gingival recession in a removable bite (8 ± 1 years old) living in the Republic of Tatarstan. DNA was isolated from buccal epithelial cells. Genotyping of the rs1544410 polymorphism of the VDR gene was performed using a real-time PCR.&#x0D; Results. A positive relationship was found for the rs1544410 T allele of the VDR gene with class II gingival recession in a removable bite according to Miller's classification (p = 0.021, r = 0.258), and recession depth (p = 0.029, r = 0.24). &#x0D; Conclusions. 1. A positive correlation was found between the risk allele T of the BsmI (rs1544410) polymorphism of the VDR gene and clinical manifestations of gingival recession in a removable bite in a sample of the population of the Republic of Tatarstan. 2. The distribution of alleles and genotypes of the BsmI (rs1544410) polymorphism of the VDR gene did not differ between the observation and control groups.

Association of cytotoxic T-lymphocyte-associated protein 4 polymorphisms with recurrent pregnancy loss: A case-control study.

A large proportion of cases of recurrent pregnancy loss (RPL) are associated with immunological factors. This study investigated the association between single nucleotide polymorphisms of cytotoxic T-lymphocyte-associated protein (CTLA)-4 gene in women with a history of RPL compared to healthy women. A case-control study was performed on 2 groups consisting of 120 healthy women with no history of abortion and at least one delivery (control) and 120 women with a history of 2 or more primary RPLs (case). In addition, 5 mL of peripheral blood sample was taken from all subjects. The frequencies of CTLA-4 rs3087243 and rs231775 polymorphisms were assayed by restriction fragment length polymorphism polymerase chain reaction and rs5742909 using the high-resolution melting real-time polymerase chain reaction method. The mean age of the women in the control and RPL groups were 30.03 4.23 (range 21-37), and 28.64 3.61 yr (range 20-35), respectively. Pregnancy loss numbers ranged between 2-6 in women with a history of RPL, and between 1 and 4 in the successful pregnancy group. Statistical analysis showed a significant difference between the genotypes of GG and AG in the 2 groups in rs3087243 polymorphism (OR 1.00 for GG genotype and OR 2.87 for AG genotype, p = 0.0043). No significant difference was observed in the genotype frequencies of rs231775 and rs5742909 polymorphisms, of the 2 groups (p = 0.37, and p = 0.095), respectively. Our findings indicated that CTLA-4 polymorphism, rs3087243, might be associated with a risk of RPL in Iranian women.