CC Genotype Research Articles

Vitamin D deficiency and the vitamin D receptor (VDR) gene polymorphism rs2228570 (FokI) are associated with an increased susceptibility to hypertension among the Bangladeshi population.

Vitamin D receptor (VDR) gene is implicated in hypertension vulnerability due to its role in regulating the renin-angiotensin system (RAS) and blood pressure. In this case-control study, a carefully selected cohort of 111 hypertensive individuals and 100 healthy controls underwent serum analysis using HPLC to measure 25-hydroxy vitamin D levels. Polymorphic variations in the VDR gene were detected and characterized using the PCR-RFLP method. At first, lower 25-hydroxy vitamin D levels were observed in hypertensive individuals compared to controls (p<0.001). The genotype frequency of the VDR gene TaqI showed no significant difference between cases and controls (p>0.05). Similarly, no significant difference was found in the VDR gene BsmI genotype frequency between hypertensive patients and controls (p>0.05). However, a statistically significant distinction was observed in the VDR gene FokI genotype frequency between cases and controls (p<0.01). The odds ratios for FokI genotypes (CC, CT, TT, and CT+TT) were 1.0, 0.590, 1.566, and 0.963, respectively. Furthermore, serum 25-hydroxy vitamin D levels were significantly higher in control subjects compared to hypertensive patients across all genotypes of VDR (p<0.001). Hypertensive patients, excluding those with the FokI VDR gene CC genotype, exhibited significantly higher systolic blood pressure levels compared to the control group (p<0.05). Similarly, hypertensive subjects displayed elevated diastolic blood pressure levels compared to the control group (p<0.001). Overall, the results suggest the presence of a potential inverse correlation between serum 25-hydroxy vitamin D levels and hypertension. The association analysis conducted indicated that there is no significant association between TaqI and bsmI genotypic variants and the risk of developing hypertension. However, it was observed that VDR gene polymorphisms do have a clear association with hypertension susceptibility, as evidenced by the significantly higher occurrence of FokI genotypic variants in hypertensive patients. Our study therefore introduces the possibility of utilizing 25-hydroxy vitamin D deficiency and VDR gene polymorphisms as a biomarker for hypertension.

Relationship between XPA, XPB/ERCC3, XPF/ERCC4, and XPG/ERCC5 Polymorphisms and the Susceptibility to Head and Neck Carcinoma: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.

Background and Objectives: Nucleotide Excision Repair (NER), the most extensively researched DNA repair mechanism, is responsible for repairing a variety of DNA damages, and Xeroderma Pigmentosum (XP) genes participate in NER. Herein, we aimed to update the previous results with a meta-analysis evaluating the association of XPA, XPB/ERCC3, XPF/ERCC4, and XPG/ERCC5 polymorphisms with the susceptibility to HNC. Materials and Methods: PubMed/Medline, Web of Science, Scopus, and Cochrane Library databases were searched without any restrictions until 18 November 2023 to find relevant studies. The Review Manager 5.3 (RevMan 5.3) software was utilized to compute the effect sizes, which were expressed as the odds ratio (OR) with a 95% confidence interval (CI). Results: Nineteen articles were involved in the systematic review and meta-analysis that included thirty-nine studies involving ten polymorphisms. The results reported that the CC genotype of rs17655 polymorphism showed a significantly decreased risk of HNC in the recessive model (OR: 0.89; 95%CI: 0.81, 0.99; p-value is 0.03). In addition, the CT genotype (OR: 0.65; 95%CI: 0.48, 0.89; p-value is 0.008) of the rs751402 polymorphism was associated with a decreased risk, and the T allele (OR: 1.28; 95%CI: 1.05, 1.57; p-value is 0.02), the TT (OR: 1.74; 95%CI: 1.10, 2.74; p-value is 0.02), and the TT + CT (OR: 2.22; 95%CI: 1.04, 4.74; p-value is 0.04) genotypes were associated with an increased risk of HNC. Conclusions: The analysis identified two polymorphisms, rs17655 and rs751402, as being significantly associated with the risk of HNC. The study underscored the influence of various factors, such as the type of cancer, ethnicity, source of control, and sample size on these associations.

Gene Polymorphisms of NLRP3 Associated With Plasma Levels of 4β-Hydroxycholesterol, an Endogenous Marker of CYP3A Activity, in Patients With Asthma.

Inflammation decreases the activity of cytochrome P450 3A (CYP3A). Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) is responsible for regulating the inflammatory response, and its genetic polymorphisms have been linked to inflammatory diseases such as asthma. However, there have been few studies on the effect of NLRP3 on CYP3A activity. We aimed to investigate the association between polymorphisms in the NLRP3 gene and plasma 4β-hydroxycholesterol (4βOHC), an endogenous marker of CYP3A activity, in patients with asthma. In this observational study including 152 adult asthma patients, we analyzed 10 NLRP3 gene single-nucleotide polymorphisms (SNPs). Plasma 4βOHC levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that five SNPs were associated with significantly lower plasma 4βOHC concentrations. Among these SNPs, rs3806265, rs4612666, rs1539019, and rs10733112 contributed to a significant increase in plasma IL-6 concentrations. Moreover, a multivariate regression model showed that the rs3806265 TT, rs4612666 CC, rs1539019 AA, and rs10733112 TT genotypes were significant factors for decreased plasma 4βOHC, even after including patient background factors and CYP3A5*3 (rs776746) gene polymorphisms as covariates. These results were also observed when plasma 4βOHC concentrations were corrected for cholesterol levels. We conclude that NLRP3 gene polymorphisms are involved in increasing plasma IL-6 concentrations and decreasing plasma 4βOHC concentrations in patients with asthma. Therefore, NLRP3 gene polymorphisms may be a predictive marker of CYP3A activity in inflammatory diseases such as asthma.

New Genetic Markers of Skin T-Cell Lymphoma Treatment.

Cutaneous T-cell lymphomas (CTCL) can be described as chronic skin inflammation lesions with the content of malignant T cells and they are considered to be T-cell-mediated skin diseases. CD147 is recognized as a 58-kDa cell surface glycoprotein of the immunoglobulin superfamily; it can induce the synthesis of MMPs (matrix metalloproteinases) on the surface of tumor cells where it was originally identified. It can also function in adjacent tumor fibroblasts using CD147-CD147 interactions. The polymorphism rs8259 T/A is situated in the untranslated region (3'UTR) of the CD147 gene. HLA DRB1*1501 takes part in the process of presentation and recognition of different antigens to T cells. It can be expressed by antigen-presenting cells-macrophages, dendritic cells, and B cells. The aim of the study is to test genotype-phenotype associations of both polymorphisms including therapy in a large cohort of CTCL patients. A final total of 104 CTCL patients were enrolled in the study. For the first remission at the clinic department, they were treated by means of local skin-directed therapy, phototherapy, and systemic therapy. Genomic DNA was isolated from peripheral blood leukocytes. A standard technique using proteinase K was applied. The polymorphisms rs8259 T/A (CD147 gene) and rs3135388 (HLA DRB1*1501) were detected through standard PCR-restriction fragment length polymorphism methods. The severity of the disease (patients with parapsoriasis, stages IA and IB, vs patients with stages IIB, IIIA, and IIIB) was associated with the CD147 genotype: the AA variant was 3.38 times more frequent in more severe cases, which reflects the decision on systemic therapy (p = 0.02, specificity 0.965). The AA genotype in the CD147 polymorphism was 12 times more frequent in patients who underwent systemic therapy of CTCL compared to those not treated with this therapy (p = 0.009, specificity 0.976). The same genotype was also associated with radiotherapy-it was observed 14 times more frequently in patients treated with radiotherapy (p = 0.009, specificity 0.959). In patients treated with interferon α therapy, the AA genotype was observed to be 5.85 times more frequent compared to the patients not treated with interferon therapy (p = 0.03, specificity 0.963). The HLA DRB1*1501 polymorphism was associated with local skin-directed therapy of CTCL. The CC genotype of the polymorphism was observed to be 3.57 times more frequent in patients treated with local therapy (p = 0.008, specificity 0.948). When both polymorphisms had been calculated together, even better results were obtained: the AACC double genotype was 11 times more frequent in patients with severe CTCL (p = 0.009, specificity 0.977). The TACT double genotype was associated with local skin-directed therapy (0.09 times lower frequency, p = 0.007, sensitivity 0.982). The AACC genotype was 8.9 times more frequent in patients treated by means of systemic therapy (p = 0.02, specificity 0.976) and as many as 18.8 times more frequent in patients treated with radiotherapy (p = 0.005, specificity 0.969). Thus, the AACC double genotype of CD147 and DRB1*1501 polymorphisms seems to be a clinically highly specific marker of severity, systemic therapy and radiotherapy of patients with T-cell lymphoma. Although genotyping results were not known during the treatment decision and could not modify it, the clinical decision on severity and therapy reflected some aspects of the genetic background of this complicated T-cell-associated disease very well.

Sirtuin-1 level and gene polymorphisms in multiple sclerosis

BackgroundSirtuin-1 (SIRT1) may affect multiple sclerosis (MS) disease. This study aimed to investigate the level of serum SIRT1, mRNA expression and genetic polymorphisms in Egyptian MS sufferers. Also, to assess its role as a possible biomarker in predicting the risk of MS and to evaluate the association between its levels and disability of MS. Measurement of SIRT1, serum level, mRNA expression level and genotyping for sirtuin-1 gene polymorphisms in 240 Egyptian subjects; 120 MS sufferers and 120 healthy control subjects.ResultsThere was a significant diminishment of level of serum sirtuin-1, and sirtuin-1 mRNA expression in MS sufferers compared to control subjects. Different sirtuin-1 single nucleotide polymorphism frequencies were statistically significant in MS sufferers compared to the control subjects. Moreover, a negative correlation of serum level of sirtuin-1 in MS sufferers with MS disease duration, disability according to Expanded Disability Status Scale (EDSS) score, cholesterol, and triglyceride serum levels. Regarding the sirtuin-1 gene polymorphisms in MS sufferers, the rs7895833 GG genotype had significant higher cholesterol, and low-density lipoprotein (LDL) levels than the GA and AA genotypes and that the rs7069102 GG genotype had a higher LDL level than the CG and CC genotypes while the rs2273773 TT genotype was significantly associated with cholesterol, and LDL levels than the TC and CC genotypes. No significant difference was detected in EDSS score comparing different sirtuin-1 genotypes among MS sufferers. In MS sufferers, rs7895833 G allele can be independently associated with cholesterol, triglycerides, and LDL levels. rs7069102 C allele can be independently associated with LDL level. With regard to rs2273773, T allele, it can be independently associated with cholesterol and LDL levels.ConclusionThere was a significant association between different sirtuin-1 gene polymorphisms and dyslipidemia which may modulate the course of MS disease. Furthermore, serum sirtuin-1 level can be considered as a possible predictor of disability in multiple sclerosis sufferers.

Association of VEGF+936 C/T Polymorphism with Susceptibility to Type 2 Diabetic Retinopathy: A Meta-Analysis.

The objective of this study is to explore the relationship between the vascular endothelial growth factor (VEGF)+936 C/T polymorphism and the risk of type 2 diabetic retinopathy (T2DR) by a method of meta-analysis. Six online databases were queried to identify studies investigating the VEGF+936 C/T polymorphism that influenced T2DR up to August 2023. The statistical tool of the pooled data was adopted using Stata 15.0 software. The experimental group comprised patients with T2DR, while patients with type 2 diabetes mellitus without retinopathy were considered as the controls. The odds ratio (OR) was utilized as effect size. Eight eligible publications were identified in this review, including 1546 patients with T2DR. The combined results revealed that the VEGF+936 C/T polymorphism was significantly associated with the T2DR risk under the allelic (C/T: OR=0.54, p<0.001), the dominant (CC+CT/TT: OR=0.37, p<0.001), recessive (CC/CT+TT: OR=0.52, p=0.001), homozygous (CC/TT: OR=0.31, p<0.001), and heterozygous (CT/TT: OR=0.55, p=0.005) gene models. No significant correlation was observed regarding the VEGF+936 C/T polymorphism that contributed to the risk of proliferative diabetic retinopathy (PDR) versus non-PDR. In conclusion, the VEGF+936 C/T polymorphism significantly contributed to the T2DR risk. Specifically, at the VEGF+936 C/T locus, the presence of allele C and genotypes CC, CT, and CC+CT were found to be associated with a reduced risk of T2DR.

Impact of ITPA gene polymorphism for predicting anemia and treatment outcome in HCV infected patients taking Sofosbuvir Ribavirin therapy

BackgroundGlobally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy.MethodsThis prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied.ResultsA total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction.ConclusionPretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.

Maternal and Offspring Fatty Acid Desaturase Variants, Prenatal DHA Supplementation, and Dietary n–6:n–3 Fatty Acid Ratio in Relation to Cardiometabolic Health in Mexican Children

BackgroundSingle-nucleotide polymorphisms (SNPs) in fatty acid desaturase (FADS) genes may modify dietary fatty acid requirements and influence cardiometabolic health (CMH). ObjectivesWe evaluated the role of selected variants in maternal and offspring FADS genes on offspring CMH at the age of 11 y and assessed interactions of genotype with diet quality and prenatal docosahexaenoic acid (DHA) supplementation. MethodsWe used data from offspring (n = 203) born to females who participated in a randomized controlled trial of DHA supplementation (400 mg/d) from midgestation to delivery. We generated a metabolic syndrome (MetS) score from body mass index, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and fasting glucose and identified 6 distinct haplotypes from 5 offspring FADS SNPs. Dietary n–6 (ω–6):n–3 fatty acid ratios were derived from 24-h recall data (n = 141). We used generalized linear models to test associations of offspring diet and FADS haplotypes with MetS score and interactions of maternal and offspring FADS SNP rs174602 with prenatal treatment group and dietary n–6:n–3 ratio on MetS score. ResultsAssociations between FADS haplotypes and MetS score were null. Offspring SNP rs174602 did not modify the association of prenatal DHA supplementation with MetS score. Among children with TT or TC genotype for SNP rs174602 (n = 88), those in the highest n–6:n–3 ratio tertile (>8.61) had higher MetS score relative to the lowest tertile [<6.67) (Δ= 0.36; 95% confidence interval (CI): 0.03, 0.69]. Among children with CC genotype (n = 53), those in the highest n–6:n–3 ratio tertile had a lower MetS score relative to the lowest tertile (Δ= –0.23; 95% CI: –0.61, 0.16). ConclusionsThere was evidence of an interaction of offspring FADS SNP rs174602 with current dietary polyunsaturated fatty acid intake, but not with prenatal DHA supplementation, on MetS score. Further studies may help to determine the utility of targeted supplementation strategies and dietary recommendations based on genetic profile.

DRD3 Predicts Cognitive Impairment and Anxiety in Parkinson's Disease: Susceptibility and Protective Effects.

A possible genetic contribution of dopamine D3 receptor (DRD3) to cognitive impairment in Parkinson's disease (PD) has yet to be investigated. To explore the effects of rs6280 (Ser9Gly) genotype on PD patients' cognitive performance and to clarify possible interactions with psychopathology. Two hundred and fifty-three consecutive PD patients underwent neurological and neuropsychological evaluations, which included: Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Dementia Rating Scale-2 (DRS-2), and Hospital Anxiety and Depression Scale (HADS). rs6280 polymorphism was genotyped for all PD patients and for 270 ethnically matched healthy volunteers (HC). Non-parametric group comparisons and logistic regressions were used for data analyses. rs6280 genotype did not differ between PD and HC groups. PD patients with rs6280 CC genotype had more impaired cognitive performance (i.e., <1st percentile of demographically adjusted norms) on DRS-2 subscales Initiation/Perseveration and Construction than those with TT genotype. These associations remained statistically significant when other covariates (e.g., demographic features, disease duration, severity of motor symptoms in OFF and ON states, anti-parkinsonian medication, and psychopathology symptoms) were taken into consideration. PD patients with rs6280 TC had less anxiety (i.e., HADS Anxiety≥11) than those with TT (p = 0.012). This association was also independent of other covariates. Study findings suggest that rs6280 CC genotype predisposes to executive dysfunction and visuoconstructional deficits, whereas the heterozygous genotype protects from anxiety in PD. These effects do not appear to be dependent of one another. rs6280 is not a genotypic susceptibility factor for PD.

No Association of Stathmin1 Gene Polymorphism with Trait or State Anxiety in the Chinese Population.

Stathmin 1 (Stmn1) is a neuronal growth-associated protein which was found to be involved in fear processing both in animals and humans. Moreover, it has been demonstrated that 2 single nucleotide polymorphisms (SNPs) of the Stmn1 gene (rs182455 and rs213641) significantly impacted individual fear and anxiety responses in German. However, there have been no reports on the correlation between Stmn1 SNPs and anxiety in Chinese. The present study thus aimed to explore such correlation. A sample of 567 healthy Han Chinese adults were genotyped for the Stmn1 SNP, namely rs182455, using polymerase chain reaction and restriction fragment length polymorphism analysis. Anxiety was assessed by the Chinese version of 40-item State-Trait Anxiety Inventory (STAI), which measures 2 anxiety dimensions, state and trait anxiety. The numbers of CC, CT, and TT genotypes of rs182455 polymorphism were 227 (40.0%), 263 (46.4%), and 77 (13.6%), respectively. The genotype distribution did not deviate from the Hardy-Weinberg equilibrium (χ 2 = 0.004, P = .953). There were no significant differences in either state or trait anxiety among the 3 rs182455 genotype groups (F = 0.457, 0.415, P = .634, .660), between the 2 dominant model groups (t = 0.865, -0.195, P = .388, .845), or between the 2 recessive model groups (t = 0.106, 0.906, P = .916, .365). Moreover, no significant gender-specific differences in any STAI scores were found among the rs182455 genotype groups (all P > .05). No evidence was demonstrated for the association of the Stmn1 gene polymorphism rs182455 with either trait or state anxiety in Chinese adults.

Distribution of the SLC2A9 genotype and its association with the uric acid level in patients with arterial hypertension and atrial fibrillation

Asymptomatic hyperuricemia (HU) is widespread in the population and is one of the main risk factors for cardiovascular diseases. Evidence of numerous studies supports the association between increased uric acid (UA) levels and the risk of arterial hypertension (HTN) and/or atrial fibrillation (AF). One of the causes for an increase in UA levels and a significant risk factor for HU is the polymorphism of the SLC2A9 gene, a highly specific urate transporter in proximal renal tubule cells, encoding the GLUT9 protein.The aim of the study is to investigate the frequency of genotypes and alleles of the SLC2A9 gene rs734553 polymorphic variant and its association with the UA level in patients with HTN and AF, as well as in healthy individuals. 141 patients, including 50 healthy patients (group 1), 68 – with HTN and AF (group 2), 23 – with HTN (group 3) were examined.In the overall group of patients, the frequencies of the SLC2A9 gene rs734553 polymorphism were as follows: AA – 46.1 % (n = 65), AC – 36.2 % (n = 51), CC – 17.7 % (n = 25). According to the genotyping results of patients, in group 1 the AA genotype was 64 % (n = 32), AC – 22 % (n = 11), CC – 14 % (n = 7); in group 2 – 32.4 % (n = 22), 48.5 % (n = 33) and 19.1 % (n = 13); in group 3 47.8 % (n = 11), 30.4 % (n = 7) and 21.7 % (n = 5), respectively. The CC genotype patients (420 [413; 424] μmol/l) and the AC genotype patients (330 [284; 412] μmol/l) had higher uricemia values than those with the AA genotype (310 [281; 341] μmol/l) ( p = 0,003). HU with the AA genotype in group 2 was diagnosed in 2 (2.9 %) patients, with the AC genotype in 12 (17.6 %), and with the CC genotype in 10 (14.7 %) patients; in group 3 – 1 (4.3 %), 1 (4.3 %) and 3 (13 %), respectively. One patient (2 %) with HU in group 1 had the CC genotype.The distribution of genotype and allele frequencies of the SLC2A9 gene rs734553 polymorphic variant and its association with the UA level in patients with HTN and AF, as well as in healthy individuals were established. In patients with HTN and AF, the AC genotype occurred 3 times more often and the CC genotype occurred 2 times more often than in healthy patients. HU occurred significantly more often ( р = 0.003) in the group of patients with HTN and AF and the CC genotype, as well as in patients with the CC genotype.

Clinical efficacy of clopidogrel and ticagrelor in patients undergoing off-pump coronary artery bypass grafting: a retrospective cohort study.

Ticagrelor is reportedly more effective than clopidogrel in preventing atherothrombotic events in patients with percutaneous coronary intervention. However, the optimal antiplatelet therapy strategy after off-pump coronary artery bypass grafting (OPCABG) is yet to be established. This study was performed using the prospectively-maintained database at our institution. Patients who underwent OPCABG were divided into the clopidogrel and the ticagrelor groups. Propensity score matching analysis was performed between the two groups. The clinical outcome was the occurrence of major adverse cardiovascular event (MACE), defined as a composite of vascular death, myocardial infarction, or stroke 1 year after surgery. In total, 545 patients completed the entire follow-up assessment. After propensity score matching, 232 patients each were included in the clopidogrel and ticagrelor groups. The primary outcome occurred in 7.8% and 4.3% of patients in the clopidogrel and ticagrelor groups, respectively (P=0.113). CYP2C19 variants (*2, *3, and *17) did not impact the clinical outcomes, regardless of the use of clopidogrel or ticagrelor. The rates of MACE were significantly lower in patients carrying the ABCB1 C3435T CT/TT genotypes in the ticagrelor group than in those carrying the ABCB1 C3435T CC genotype in the clopidogrel group (1.4% vs. 9.1%, adjusted P=0.030), as well as those carrying the ABCB1 C3435T CC genotype in the ticagrelor group (1.4% vs. 8.9%, adjusted P=0.036). The ABCB1 C3435T CC genotype was significantly associated with the incidence of 1-year MACE (HR=1.558, 95% CI 1.109-2.188, P=0.011). Patients who experienced severe perioperative bleeding exhibited a significantly higher incidence of MACE than those who did not experience severe perioperative bleeding (14.0% vs. 4.9%, adjusted P=0.007). There was no significant difference in the 1-year MACE between patients receiving clopidogrel and those receiving ticagrelor after OPCABG. Notably, The ABCB1 C3435T CC genotype was related to a higher risk of MACE.

Abstract P18: Splicing polymorphism rs12459419 modulates antibody-bound internalization of CD33 isoforms

Abstract P18: Splicing polymorphism rs12459419 modulates antibody-bound internalization of CD33 isoforms

The prevalence of ADSL (rs3788579) and CYP1A2 (rs17861162) polymorphisms in female breast cancer patients in North-West Iran

IntroductionBreast cancer is a prevalent and significant contributor to cancer-related mortality among women worldwide. Its increasing incidence, especially in regions like North-West Iran, necessitates a deeper understanding of genetic factors contributing to its development. Genetic alterations, particularly single nucleotide polymorphisms (SNPs), are implicated in breast cancer susceptibility, making investigation in this context crucial. This study explores the role of CYP1A2-rs17861162 and ADSL-rs3788579 SNPs in breast cancer risk among Iranian women.MethodsThis study involved 200 female breast cancer patients and 200 healthy controls in North-West Iran. DNA was extracted from blood samples, and PCR–RFLP was used for genotyping the CYP1A2 and ADSL genes.ResultsThe CYP1A2-rs17861162 SNP exhibited a shift from the C allele to the G allele in breast cancer patients, resulting in a 21.7% decrease in CC genotype frequency and a 21.6% and 77.8% increase in CG and GG genotypes, respectively, compared to controls. In ADSL-rs3788579 SNP, breast cancer patients had a significantly higher prevalence of the T allele, with a 28.5% increase compared to controls. In healthy participants, CC was most common, while in the breast cancer group, TT was most common.ConclusionThis study highlights significant genetic alterations in CYP1A2-rs17861162 and ADSL-rs3788579 SNPs among breast cancer patients in North-West Iran, suggesting their potential as diagnostic and prognostic biomarkers. Further research is warranted to elucidate the precise mechanisms underlying their contributions to breast cancer susceptibility in this population.

The Association of Vitamin D Receptor Polymorphisms with COVID-19 Severity.

Association studies of vitamin D receptor (VDR) polymorphisms with COVID-19 severity have produced inconsistent results in different populations. Herein we examined VDR gene polymorphisms in a Caucasian Greek cohort of COVID-19 patients. This was a case-control study in a tertiary university hospital in Greece including 137 COVID-19 patients with varying disease severities and 72 healthy individuals. In total 209 individuals were genotyped for the FokI (rs10735810), ApaI (rs7975232), TaqI (rs731236) and BsmI (rs1544410) single-nucleotide polymorphisms (SNP) of the VDR gene by polymerase chain reaction and restriction fragment length polymorphism analysis (PCR-RFLPs). Statistical analyses were performed to determine the association between genotype and disease severity, adjusting for various confounding factors. Genotype distribution of the studied VDR SNPs in the control group was in Hardy-Weinberg equilibrium. The TaqI variant was differentially distributed between controls and COVID-19 patients according to the additive model (p = 0.009), and the CC genotype was significantly associated with an increased risk for severe COVID-19 according to the recessive model [OR: 2.52, 95%CI:1.2-5.29, p = 0.01]. Multivariate analysis demonstrated a robust association of COVID-19 severity and TaqI polymorphism in the recessive model even after adjusting for multiple confounders, including age, sex and CRP levels [Adj.OR:3.23, 95%CI:1.17-8.86, p = 0.023]. The distribution of FokI, ApaI and BsmI genotypes was similar between COVID-19 patients and controls. The CC genotype of TaqI polymorphism is significantly associated with an increased risk for severe COVID-19 independently of age, sex or degree of inflammation.

Role of polymorphism in vitamin D receptor gene on diabetic foot ulcer: A systematic review and meta-analysis

Context: Once vitamin D is converted to its active form, the molecule binds to its receptor (VDR) and performs its function as a transcription factor in modulating immune response, inflammation cascade, and insulin signaling. Among diabetic individuals, these activities are thought to be correlated with foot ulceration. Gene polymorphisms could change the function of VDR, thereby affecting the development of foot ulceration among individuals with diabetes. Aims: To construct evidence on the role of VDR gene variants or single nucleotide polymorphisms (SNPs) on diabetic foot ulcers. Methods: Records reporting the distribution of genotypes and/or alleles among diabetic foot ulcer (DFU) patients and published until 10 March 2023 were retrieved from 12 major databases using predetermined keywords. The original research articles included in the study were assessed for reporting quality using the Newcastle Ottawa Scale. The quality of genotypic and allelic data was appraised by Hardy-Weinberg equilibrium (HWE). A quantitative analysis-based fixed-effects model was performed to estimate the proportion of genotype and allele frequencies among DFU patients. Results: Three studies were included in the systematic review reporting the FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232) SNPs. Based on pooled estimates, among DFU patients CC, CT, and TT genotypes of VDR FokI SNPs had a prevalence of 45%, 43%, and 12%, respectively, without significant heterogeneity found in the reported data (p-Het&lt;0.001; I2&gt;0%). ApaI and FokI were associated with DFU, while no association in all genotypic and allelic models was found between TaqI or BsmI and DFU. CC genotype of BsmI and T allele of FokI was associated with oxidative stress (one of the underlying factors in DFU). Conclusions: Certain genotypes and alleles of FokI and ApaI SNPs could act as the risk factor for foot ulceration among diabetic individuals. More high-quality studies are still needed to draw solid conclusions on the role of VDR SNPs among DFU patients.

Polymorphisms of IFN signaling genes and FOXP4 influence the severity of COVID-19

BackgroundThe clinical manifestations of COVID-19 range from asymptomatic, mild to moderate, severe, and critical disease. Host genetic variants were recognized to affect the disease severity. However, the genetic landscape differs among various populations. Therefore, we explored the variants associated with COVID-19 severity in the Guangdong population.MethodsA total of 314 subjects were selected, of which the severe and critical COVID-19 patients were defined as “cases”, and the mild and moderate patients were defined as “control”. Twenty-two variants in interferon-related genes and FOXP4 were genotyped using the MassARRAY technology platform.ResultsIFN signaling gene MX1 rs17000900 CA + AA genotype was correlated with a reduced risk of severe COVID-19 in males (P = 0.001, OR = 0.050, 95%CI = 0.008–0.316). The AT haplotype comprised of MX1 rs17000900 and rs2071430 was more likely to protect against COVID-19 severity (P = 6.3E-03). FOXP4 rs1886814 CC genotype (P = 0.001, OR = 3.747, 95%CI = 1.746–8.043) and rs2894439 GA + AA genotype (P = 0.001, OR = 5.703, 95% CI = 2.045–15.903) were correlated with increased risk of severe COVID-19. Haplotype CA comprised of rs1886814 and rs2894439 was found to be correlated with adverse outcomes (P = 7.0E-04). FOXP4 rs1886814 CC (P = 0.0004) and rs2894439 GA + AA carriers had higher neutralizing antibody titers (P = 0.0018). The CA + AA genotype of MX1 rs17000900 tended to be correlated with lower neutralizing antibody titers than CC genotype (P = 0.0663), but the difference was not statistically significant.ConclusionOur study found a possible association between MX1 and FOXP4 polymorphisms and the severity of COVID-19. Distinguishing high-risk patients who develop severe COVID-19 will provide clues for early intervention and individual treatment strategies.

ВСТРЕЧАЕМОСТЬ ПОЛИМОРФИЗМА ГЕНОВ COL1A1, VDR У ПАЦИЕНТОВ С КОСТНЫМИ КИСТАМИ

Background. The relationship between the decrease in bone mineral density, a violation of bone metabolism and functionally defective alleles of the VDR and SOL1A1 genes was proved. Taking into account the peculiarities of bone biodynamics and the fact that in the period from 5 to 16 years, the bone mineral density increases by 3 times, which coincides with the age period for the detection of bone cysts in children, the study of polymorphism of the VDR and COL1A1 genes (which mainly regulate bone formation) in patients with bone cysts is relevant today. Aim. To investigate the polymorphism of collagen type 1 (COL1A1), vitamin D receptor (VDR) genes in children with bone cysts, to establish the influence of the gene factor on the development of this pathology. Material and methods. During the period from June to December 2021, the polymorphism COL1A1, VDR was studied in 27 patients diagnosed with bone cysts. 41 patients with other orthopedic and traumatological pathology were examined as comparison groups. Genotyping of polymorphic alleles of the VDR and COL1A1 gene was performed by "real time" polymerase chain reaction. Results. In patients with bone cysts, the frequency of heterozygous genotype AG and homozygous GG was the same – 37% for each, the AA genotype accounted for 26%. In children from the comparison group, heterozygous genotype AG and homozygous AA were found with the same frequency – 39% each, genotype GG – 22% each. In patients with bone cysts, the frequency of homozygous genotype AA and heterozygous CA was the same – 15% for each, the CC genotype accounted for 70%. In children from the comparison group, homozygous genotype CC was found in 70.5% of cases, heterozygous genotype CA – 27%, homozygous genotype AA – 2.5%. Conclusions. It was found that the percentage of mutant homozygous type for the VDR and COL1A1 genes is higher in patients with bone cysts. There is a certain genetically determined relationship between bone cysts and a violation of bone formation and bone resorption.

SIRT3 rs11246020 Polymorphism Associated Postprandial Triglyceride Dysmetabolism.

Energy metabolism is regulated by SIRT3, no research has been done on the connection between lipid metabolism in the oral fat test and SIRT3 polymorphism. Thus, we conducted a case-control study to investigate the connection between postprandial lipid and SIRT3 polymorphism. 402 non-obese Chinese subjects were enrolled and their postprandial lipid response to oral fat tolerance test (OFTT) was observed to understand the relationship between rs11246020 gene and postprandial triglyceride metabolism. In a binary logic regression model, a protective effect of the T allele of the rs11246020 SIRT3 for postprandial hypertriglyceridemia was shown (OR=0.417, 95% CI = 0.219-0.794, p=0.008). Compared to the CC genotype, individuals with the TT+CT variant of the rs11246020 SIRT3 gene demonstrated significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.04), postprandial plasma glucose (PPG) (p=0.037), fasting plasma glucose (FPG) (p=0.02), and 4-hour triglyceridemia (Tg) (p=0.032). The C allele of rs11246020 SIRT3 gene may be a risk factor to increased possibility of postprandial triglyceridemia after an oral fat test, which involved in the mechanism of glucose and insulin metabolism.

TNFRSF1B Gene Variants in Clinicopathological Aspects and Prognosis of Patients with Cutaneous Melanoma.

Regulatory T lymphocytes play a critical role in immune regulation and are involved in the aberrant cell elimination by facilitating tumor necrosis factor connection to the TNFR2 receptor, encoded by the TNFRSF1B polymorphic gene. We aimed to examine the effects of single nucleotide variants TNFRSF1B c.587T>G, c.*188A>G, c.*215C>T, and c.*922C>T on the clinicopathological characteristics and survival of cutaneous melanoma (CM) patients. Patients were genotyped using RT-PCR. TNFRSF1B levels were measured using qPCR. Luciferase reporter assay evaluated the interaction of miR-96 and miR-1271 with the 3'-UTR of TNFRSF1B. The c.587TT genotype was more common in patients younger than 54 years old than in older patients. Patients with c.*922CT or TT, c.587TG or GG + c.*922CT or TT genotypes, as well as those with the haplotype TATT, presented a higher risk of tumor progression and death due to the disease effects. Individuals with the c.*922TT genotype had a higher TNFRSF1B expression than those with the CC genotype. miR-1271 had less efficient binding with the 3'-UTR of the T allele when compared with the C allele of the SNV c.*922C>T. Our findings, for the first time, demonstrate that TNFRSF1B c.587T>G and c.*922C>T variants can serve as independent prognostic factors in CM patients.