Rs2910164 Polymorphism Research Articles

DEVELOPMENT OF A METHOD FOR GENOTYPING THE 𝘔𝘛𝘏𝘍𝘙 RS1801133 POLYMORPHISM IN VIETNAMESE, USING THE POLYMERASE CHAIN REACTION WITH CONFRONTING TWO-PAIR PRIMERS

Aims: To develop a method using polymerase chain reaction with confronting two-pair primers (PCR-CTPP) to genotype MTHFR rs1801133 polymorphism in Vietnamese people. Methods: DNA samples from 15 Vietnamese people were used to evaluate this assay. The Sanger sequencing method was used to identify the standard genotypes of the rs1801133 polymorphism. Some bioinformatic softwares were used to design four a multiplex PCR-CTPP. Experimental procedures were conducted to verify the primers and components of the PCR method. Results: The protocol of the PCR-CTPP was successful developed with optimal inner/outer primers ratio, the melting temperature of primers, the components and the thermal cycling to identify MTHFR rs1801133 polymorphism. Conclusion: The PCR-CTPP protocol should be applied to genotyping MTHFR rs1801133 polymorphism in large cohorts to investigate the association between the polymorphism and metabolic syndrome in Vietnamese population.

Personalization of Anticoagulant Therapy with Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Chronic Kidney Disease Based on Pharmacogenetic Testing

Background. Polymorphic variants of the genes encoding these isoenzymes and carrier proteins involved in the pharmacokinetics of direct oral anticoagulants (DOAC) may alter their function and, therefore, hypothetically may increase the risk of bleeding associated with the use of DOAC. Aims to study the possible relationship between the presence of polymorphic variants of ABCB1 (rs2032582, rs1045642, rs1128503), CYP3A5 (rs776746) and CYP3A4 (rs35599367) genes on the residual equilibrium concentration (Cmin,ss /D) of apixaban, CYP3A isoenzyme activity and bleeding development in patients with AF and CKD C3C4 stages. Methods. The study included 142 patients with AF combined with chronic CKD stages C3 and C4, receiving apixaban therapy, aged 58 to 99 years (median age 84 years). Pharmacogenetic, pharmacokinetic testing and assessment of CYP3A isoenzyme group activity were performed. Results. Plasma concentration of apixaban depended on the stage of CKD: a higher level of Cmin,ss /D was observed in patients with CKD stage C4 compared to patients with CKD stage C3a and with CKD stage C3b. When studying the effect of rs1045642 (C3435T) polymorphism of ABCB1 gene on apixaban pharmacokinetics, it was found that carriers of homozygous TT genotype had lower median apixaban concentration in blood compared to carriers of CC and TC genotypes (p = 0.027 and 0.034 respectively). For rs2032582 polymorphism of ABCB1 gene, we recorded that patients with GG genotype had higher Cmin,ss /D level of apixaban compared to GT genotype carriers (p = 0.037). CYP3A metabolic activity was statistically significantly lower (p = 0.036) in the group with a history of bleeding compared with that in patients in the group without a history of bleeding (0.8 (0.5; 1.3) and 1.2 (0.7; 2.1); p = 0.036). CYP3A metabolic activity did not differ between patients with different CYP3A5 (rs776746) and CYP3A4 (rs35599367) polymorphism genotypes. For the rs1045642 polymorphic variant, there were fewer carriers of the heterozygous TC genotype (16 (45.7%) patients) among patients with bleeding during the follow-up period compared to patients with no bleeding (43 (53.1%) patients; p = 0.024). Conclusions. The results of the study indicate the presence of an association between genome-wide changes (polymorphic variants of the ABCB1 (rs1045642) and CYP3A5 (rs776746) gene and the presence of apixaban-associated bleeding in patients with AF and CKD stages 34. Mechanisms of such an association require further study.

Prognostic role and interaction of TERT promoter status, telomere length and MGMT promoter methylation in newly diagnosed IDH wild-type glioblastoma patients

The clinical relevance of promoter mutations and single nucleotide polymorphism rs2853669 of telomerase reverse transcriptase (TERT) and telomere length in patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) patients remains unclear. Moreover, some studies speculated that TERT promoter status might influence the prognostic role of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in newly diagnosed GBM. We carried out a large study to investigate their clinical impact and their interaction in newly diagnosed GBM patients. We included 273 newly diagnosed IDH wild-type GBM patients who started treatment at Veneto Institute of Oncology IOV - IRCCS (Padua, Italy) from December 2016 to January 2020. TERT promoter mutations (-124 C>T and-146 C>T) and SNP rs2853669 (-245 T>C), relative telomere length (RTL) and MGMT methylation status were retrospectively assessed in this prospective cohort of patients. Median overall survival (OS) of 273 newly diagnosed IDH wild-type GBM patients was 15 months. TERT promoter was mutated in 80.2% of patients, and most had the rs2853669 single nucleotide polymorphism as T/T genotype (46.2%). Median RTL was 1.57 (interquartile range 1.13-2.32). MGMT promoter was methylated in 53.4% of cases. At multivariable analysis, RTL and TERT promoter mutations were not associated with OS or progression-free survival (PFS). Notably, patients C carrier of rs2853669 (C/C+C/T genotypes) showed a better PFS compared with those with the T/T genotype (hazard ratio 0.69, P= 0.007). In terms of OS and PFS, all interactions between MGMT, TERT and RTL and between TERT and rs2853669 genotype were not statistically significant. Our findings suggest the presence of the C variant allele at the rs2853669 of the TERT promoter as an attractive independent prognostic biomarker of disease progression in IDH wild-type GBM patients. RTL and TERT promoter mutational status were not correlated to survival regardless of MGMT methylation status.

MiR-146a rs2910164 (G/C) polymorphism is associated with the development and prognosis of acute coronary syndromes: an observational study including case control and validation cohort

BackgroundPolymorphisms in microRNAs (miRNAs) play an important role in acute coronary syndromes (ACS). The purpose of this study was to assess the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with the development and prognosis of ACS and to explore the underlying mechanisms.MethodsA case–control study of 1171 subjects was included to determine the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with ACS risk. An additional 612 patients with different miR-146a rs2910164 genotypes, who underwent percutaneous coronary intervention (PCI) were included in the validation cohort and followed for 14 to 60 months. The endpoint was major adverse cardiovascular events (MACE). A luciferase reporter gene assay was used to validate the interaction of oxi-miR-146a(G) with the IKBA 3'UTR. Potential mechanisms were validated using immunoblotting and immunostaining.ResultsThe miR-146a rs2910164 polymorphism was significantly associated with the risk of ACS (Dominant model: CG + GG vs. CC, OR = 1.270, 95% CI (1.000–1.613), P = 0.049; Recessive model: GG vs. CC + CG, OR = 1.402, 95% CI (1.017–1.934), P = 0.039). Serum inflammatory factor levels were higher in patients with the miR-146a rs2910164 G allele than in those with the C allele. MiR-146a rs2910164 polymorphism in dominant model was associated with the incidence of MACE in post-PCI patients (CG + GG vs. CC, HR = 1.405, 95% CI (1.018–1.939), P = 0.038). However, the miR-34b rs4938723 polymorphism was not associated with the prevalence and prognosis of ACS. The G allele of miR-146a rs2910164 tends to be oxidized in ACS patients. The miRNA fractions purified from monocytes isolated from ACS patients were recognized by the 8OHG antibody. Mispairing of Oxi-miR-146a(G) with the 3'UTR of IKBA results in decreased IκBα protein expression and activation of the NF-κB inflammatory pathway. P65 expression was higher in atherosclerotic plaques from patients carrying the miR-146a rs2910164 G allele.ConclusionThe variant of miR-146a rs2910164 is closely associated with the risk of ACS in Chinese Han population. Patients carrying miR-146a rs2910164 G allele may have worse pathological change and poorer post-PCI prognosis, partly due to the oxidatively modified miR-146a mispairing with 3′UTR of IKBA and activating NF-κB inflammatory pathways.

Association between Susceptibility to Systemic Lupus Erythematous and Polymorphisms in miR-146a and miR-499: A Meta-Analysis

Introduction: This study aimed to determine whether miR-146a and miR-499 polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE). Methods: We searched the MEDLINE, EMBASE, and Cochrane databases. We performed a meta-analysis on the association of miR-146a rs2910164, rs2431697, rs57095329, and miR-499 rs3746444 polymorphisms with susceptibility to SLE. Results: Twenty-one studies from 17 reports, with 18,910 patients and 29,622 controls, were included in the meta-analysis. Meta-analysis revealed no association between SLE and the rs2910164 C allele (odds ratio [OR] = 0.999, 95% confidence interval [CI] = 0.816–1.222, p = 0.990). Stratification by ethnicity indicated no association between the miR-146a C allele and SLE in Arab or Latin American populations. The meta-analysis revealed an association between SLE and the miR-499 rs374644 CC + CT genotype in the overall group (OR = 1.313, 95% CI = 1.015–1.698, p = 0.038). Furthermore, meta-analysis revealed a significant association between SLE and the miR-146a rs2431697 C allele in the overall group (OR = 0.746, 95% CI = 0.697–0.798, p = 0.038). The miR-146a rs2431697 C allele is protective against SLE risk. Stratification by ethnicity indicated an association between the miR-146a rs2431697 C allele and SLE in Asian and European, but not Arab populations. The meta-analysis showed an association between the miR-146a rs57095329 G allele and SLE in Asian, but not Arab populations. Discussion/Conclusion: This meta-analysis suggests that the miR-146a rs2431697 polymorphism is a protective factor against the risk of SLE, and that the miR-146a rs57095329 and miR-499 rs3746444 polymorphisms are associated with susceptibility to SLE. However, miR-146a rs2910164 was not associated with susceptibility to SLE.

Effect of ERCC1 polymorphisms on the response to platinum-based chemotherapy: A systematic review and meta-analysis based on Asian population.

Platinum-based chemotherapy is one of the most common treatments for many cancers; however, the effect of chemotherapy varies from individual to individual. Excision repair cross complementation group 1 (ERCC1) is widely recognized as a key gene regulating nucleotide excision repair (NER) and is closely associated with platinum response. Many studies have yielded conflicting results regarding whether ERCC1 polymorphisms can affect the response to platinum and overall survival (OS). Therefore, it is necessary to perform a meta-analysis of patients with specific races and cancer types. Eight databases (EMBASE, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, Scopus, VIP, China Biology Medicine disc and Wanfang databases) were searched. Results were expressed in terms of odds ratios (ORs), hazard ratios (HRs) and 95% CIs. In this study, rs11615, rs2298881 and rs3212986 SNPs were studied. In the comparison between CT and TT on the response to platinum, esophageal cancer [I2 = 0%, OR = 6.18, 95% CI(1.89,20.23), P = 0.003] and ovarian cancer [I2 = 0%, OR = 4.94, 95% CI(2.21,11.04), P<0.001] showed that the rs11615 CT genotype predicted a better response. In the comparison between CC and TT, ovarian cancer [I2 = 48.0%, OR = 6.15, 95% CI (2.56,14.29), P<0.001] indicated that the CC genotype predicted a better response. In the meta-analysis of OS, the CC genotype was related to longer OS than TT in ovarian cancer [TT vs CC: I2 = 57.7%, HR = 1.71, 95% CI (1.18, 2.49), P<0.001]. The ERCC1 rs11615 polymorphism was related to the response to platinum and OS, but the correlation is based on specific cancer types in the Asian population.

The impact of single nucleotide polymorphisms in MTHFR and MTRR genes on disease activity and the presence of methotrexate treatment side effects in children with juvenile idiopathic arthritis.

To determine the impact of single nucleotide polymorphisms (SNPs) in MTHFR and MTRR genes on disease activity and the presence of MTX therapy adverse events in Polish children with juvenile idiopathic arthritis (JIA). SNP genotyping was performed using genomic DNA isolated from peripheral blood samples. Patients with MTHFR rs1801133 CT/TT variant had higher values of inflammatory markers, number of joints with active arthritis, and JADAS-71 value at the baseline of MTX treatment. Children with MTRR rs1801394 AG/AA variant presented higher inflammatory marker values at JIA diagnosis. MTHFR rs1801133 and MTRR rs1801394 polymorphisms are associated with higher disease activity at the moment of JIA diagnosis.

Identification of Functionally Significant Polymorphic Variants in miRNA Genes in Carotid Atherosclerosis

miRNAs are vital molecules of gene expression. They are involved in the pathogenesis of various common diseases, including atherosclerosis, its risk factors and complications. A detailed characterization of the spectrum of functionally significant polymorphisms of miRNA genes of patients with advanced carotid atherosclerosis is an actual research task. We analyzed miRNA expression and exome sequencing data of carotid atherosclerotic plaques of the same male patients (n = 8, 66–71 years of age, 67‒90% degree of carotid artery stenosis). For further study and analysis of the association between rs2910164 polymorphism of the MIR146A gene and advanced carotid atherosclerosis, we recruited 112 patients and 72 relatively healthy Slavic residents of Western Siberia. 321 and 97 single nucleotide variants (SNVs) were detected in the nucleotide sequences of pre- and mature miRNAs in carotid atherosclerotic plaques. These variants were located in 206 and 76 miRNA genes, respectively. Integration the data of exome sequencing and miRNA expression revealed 24 SNVs of 18 miRNA genes which were processed to mature form in carotid atherosclerotic plaques. SNVs with the greatest potential functional significance for miRNA expression predicted in silico were rs2910164:CG (MIR146A), rs2682818:AC (MIR618), rs3746444:AG (MIR499A), rs776722712:CT (MIR186), rs199822597:GA (MIR363). The expression of miR-618 was lower in carotid atherosclerotic plaques of patients with the AC rs2682818 genotype of the MIR618 gene compared with the CC genotype (log2FC = 4.8; p = 0.012). We also found the association of rs2910164:C (MIR146A) with the risk of advanced carotid atherosclerosis (OR = 2.35; 95% CI: 1.43–3.85; p = 0.001). Integrative analysis of polymorphism in miRNA genes and miRNA expression is informative for identifying functionally significant polymorphisms in miRNA genes. The rs2682818:AC (MIR618) is a candidate for regulating miRNA expression in carotid atherosclerotic plaques. The rs2910164:C (MIR146A) is associated with the risk of advanced carotid atherosclerosis.

Patients with Non-Alcoholic Fatty Liver Disease and Alcohol Dehydrogenase 1B/Aldehyde Dehydrogenase 2 Mutant Gene Have Higher Values of Serum Alanine Transaminase.

Patients with non-alcoholic fatty liver disease (NAFLD) share similar pathophysiologies to those of patients with alcohol liver disease. Alcoholic metabolic enzyme-related genes (alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2)) may be associated with pathophysiology in NAFLD patients. In this study, the association between ADH1B/ALDH2 gene polymorphism and serum metabolic factors, body statures, and hepatic steatosis/fibrosis status was evaluated in patients with NAFLD. Using biochemistry data, abdominal ultrasonography, fibrosis evaluation (Kpa), and steatosis evaluation (CAP), ADH1B gene SNP rs1229984 and ALDH2 gene SNP rs671 polymorphism were analyzed in sixty-six patients from 1 January 2022 to 31 December 2022. The percentage of the mutant type (GA + AA) was 87.9% (58/66) in the ADH1B allele and 45.5% (30/66) in the ALDH2 allele. Patients with the mutant-type ADH1B/ALDH2 allele had higher values of alanine aminotransferase (ALT) than the wild type (β = 0.273, p = 0.04). No association was observed between body mass index, serum metabolic factors (sugar and lipid profile), CAP, kPa, and ADH1B/ALDH2. A high proportion of the mutant-type ADH1B allele (87.9%) and ALDH2 allele (45.5%) was observed in patients with NAFLD. No association was observed between ADH1B/ALDH2 allele, BMI, and hepatic steatosis/fibrosis. Patients with the mutant-type ADH1B/ALDH2 allele had higher values of ALT than those with the wild type.

Association of SOD2 Polymorphism (Rs4880) and Competitive Performance in Track and Field Athletes

The rs4880 polymorphism in the SOD2 gene has frequently been associated with the athletic performance of the athletes in different populations. However, there were not any studies in the Turkish elite athletes. Thus, the aim of the study is to evaluate the impacts of SOD2 rs4880 polymorphism on competitive performance of Turkish elite athletes. A total of 60 elite athletes (31 sprint/power and 29 endurance) and 20 controls with the ages of 18-35 voluntarily participated in the study. World Athletics (WA) score table was used to determine the performance levels of the competitive performance/personal best (PB) of the athletes. Whole exome sequencing (WES) was performed by the genomic DNA isolated from peripheral blood of the participants. Sport type, sex and competitive performance were chosen as the parameters to compare within and between the groups by linear regression models. There were not any significances between the genotype and allele frequencies. Finally, there were not any associations between competitive performance and genotype frequencies within the sprint/power athletes while competitive performance was significantly (p=0.049) correlated with rs4880 polymorphism according to the over-dominant model within the endurance athletes. The rs4880 polymorphism in the SOD2 gene may be linked to the competitive performance of the endurance athletes. Still, further studies with more participants and analyzing multiple factors are needed.

ALDH2 rs671 Polymorphism Likely a Risk Factor for Hemorrhagic Stroke: A Hospital-Based Study.

Hypertension is the main risk factor for hemorrhagic stroke. Aldehyde dehydrogenase 2 (ALDH2) may inhibit the occurrence of hypertension by anti-oxidative stress and vascular dilation. The purpose was to investigate the relationship of ALDH2 polymorphisms with hemorrhagic stroke in Hakka Chinese. A total of 329 patients with hemorrhagic stroke and 515 controls were enrolled, and medical records (smoking and drinking history, hypertension, and diabetes) were collected. The genotypes of ALDH2 rs671 of the two groups were detected and analyzed. The proportion of the ALDH2 rs671 G/G, G/A, and A/A genotype in patients with hemorrhagic stroke was 55.9%, 37.4%, and 6.7%, respectively, while those were 65.0%, 30.7%, and 4.3% in controls, respectively. There was statistically significant difference in ALDH2 rs671 genotypes distribution (P=0.021) and alleles distribution (P=0.005) between patients and controls. Among hemorrhagic stroke patients, no statistically significant differences were observed between patients with ALDH2 different genotypes. Logistic regression analysis showed that there was significantly high risk of hemorrhagic stroke in men (male vs female: adjusted OR 1.711, 95% CI 1.154-2.538, P=0.008), the presence of hypertension (with vs without hypertension: adjusted OR 16.095, 95% CI 10.958-23.641, P<0.001), and the presence of ALDH2 rs671 G/A genotype (G/A vs G/G: adjusted OR 1.679, 95% CI 1.151-2.450, P=0.007) or A/A genotype (A/A vs G/G: adjusted OR 2.516, 95% CI 1.132-5.591, P=0.024). ALDH2 rs671 polymorphism likely a risk factor for hemorrhagic stroke.

Association of Methylenetetrahydrofolate Reductase (MTHFR) Gene C677T (rs1801133) polymorphism among Sudanese patients with chronic myelogenous leukemia

Association of Methylenetetrahydrofolate Reductase (MTHFR) Gene C677T (rs1801133) polymorphism among Sudanese patients with chronic myelogenous leukemia

Association of Methylenetetrahydrofolate Reductase (MTHFR) Gene C677T (rs1801133) polymorphism among Sudanese patients with chronic myelogenous leukemia

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular folate metabolism which plays an important role in carcinogenesis through DNA methylation. Objectives: The current study aimed to determine the association between MTHFR C677T polymorphisms and the risks of chronic myeloid leukemia (CML). Material and methods: This are hospital based cross sectional case control study, a total of 170 Sudanese subjects were enrolled, and 75 patients with chronic myeloid leukemia and 75 age- and sex matched healthy volunteers as a control group. Genomic DNA was extracted by sodium chloride method and The SNPs genotypes were determined using polymerase chain reaction followed by restriction fragment length polymorphism method. (PCR- RFLP). Data of this study were collected using a structured interview questionnaire and analyzed by statistical package for social sciences (version 21). Results: The frequency of the CC genotype was higher in the control group compared with patients (100%,96%), while of the CT genotype was higher in the case (4%) than in control (0.0%); the TT genotype was absent in both study groups, the frequencies T and C allele were 0.02 and 0.98 in CML patient group and 0.00, 0.100 respectively in the control group. There was no clinically significant association between age (P.value= 0.3), gender (P.value= 0.4) and genotype, also there was no statistically significant association when compare case with control genotype (p. value 0.08). Conclusion: C677T MTHFR polymorphism is not associated with the risk of CML among the Sudanese population

Methylenetetrahydrofolate reductase polymorphisms and elevated plasma homocysteine levels in small vessel disease.

Despite its public health importance, the causes of small vessel disease (SVD) are not fully understood. The presence of SVD in monogenic twins indicates the involvement of genetic factors in the pathogenesis of this disease. The purpose of this study was to investigate the association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with SVD risk. Patients with SVD and matched controls were recruited from Tianjin Union Medical Center and Tianjin Huanhu Hospital. Clinical and laboratory data were collected. Plasma total homocysteine (tHcy) and folate levels were measured, and MTHFR rs1801133 (C677T) and rs1801131 (A1298C) single-nucleotide polymorphisms were genotyped. We analyzed potential associations among SVD and MTHFR polymorphisms, tHcy, and folate levels. Patients with SVD displayed significantly decreased plasma folate levels (Z=-3.537, p<.001) and increased tHcy levels (Z=4.910, p<.001) compared with controls. Significantly different plasma tHcy levels were associated with rs1801133 (χ2 =6.664, p=.036), and post hoc analysis indicated higher plasma tHcy levels in individuals carrying the TT allele compared with levels in those carrying the TC allele (Z=2.478, p=.013). No significant differences in tHcy levels were observed for rs1801131 alleles. The genotype and allele frequencies of rs1801133 were different between SVD and control groups (χ2 =9.378, p=.009). There was no significant difference in distributions of rs1801131 genotypes between the two groups, and multivariable logistic regression analysis showed that rs1801131 and rs1801133 were not significantly associated with the risk of SVD. Our study indicates that an elevated plasma tHcy level is independently associated with the development of SVD. Although MTHFR rs1801133 is linked to increased plasma homocysteine (Hcy) levels, it is not a risk factor for SVD. rs1801131 is not related to Hcy levels or SVD risk.

Commentary: Association between the miR-146a rs2910164 polymorphism and childhood acute lymphoblastic leukemia susceptibility in an Asian population.

GENERAL COMMENTARY article Front. Genet., 20 March 2023Sec. Statistical Genetics and Methodology Volume 14 - 2023 | https://doi.org/10.3389/fgene.2023.1134659

Assessment of miR-146a Gene Polymorphisms in Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a multifactorial chronic autoimmune disease, with a wide spectrum of effect. The main feature of the disease is the production of a wide variety of autoantibodies as a result of immune tolerance loss. The work aims to evaluate the miRNA-146a gene polymorphism potential association with disease activity and chronicity changes in SLE patients. The study included 100 SLE patients and 50 matched controls. The systemic lupus erythematosus disease activity index (SLEDAI) was assessed. The single nucleotide polymorphism (SNP) of miR-146a gene (rs2910164) polymorphism was assayed by polymerase chain reaction (PCR) and sequencing technique in patients and control. 100 SLE patients were all females and with a mean of age 31.3 ± 10 years (16-63years) and disease duration of 5.8 ± 3.7years (1 month to 15 years). Most clinical manifestations presented in patients were 52% malar rash, 45% oral ulcers, 54% arthritis, and 45% neurological disorder. Proteinuria, ESR, creatinine and AST were significantly higher (65% vs. 10%, 4.1±36.1 vs. 11.8±9.9 mm/hr, 0.62±0.11 vs. 0.70±0.14 mg/dl and 25.37±26.50 vs. 17.23±3.58 U/L respectively) while the PLT was significantly lower (231.9±88.8 vs. 282.3±67.3 103/mL) (p&lt; 0.001) among SLE patients as compared to control. There were no significant variations in all study parameters across miRNA-146a genotypes (p greater than 0.05). There was a significant association of the homozygote GG genotype (66.7%) with the active SLE state (p=0.013). In conclusion, the results suggest a risk effect for the female gender and adult at a young age in the etiology of SLE. The miRNA-146a GG genotype is associated with increasing the disease activity and miRNA-146a polymorphism is not associated with the risk in SLE.

Influence of &lt;i&gt;ABCB1&lt;/i&gt; &lt;i&gt;3435C&gt;T&lt;/i&gt; polymorphism on methotrexate safety in patients with psoriasis

Background. Methotrexate is a highly effective systemic treatment for moderate to severe psoriasis, but drug toxicity may limit its use. Recent evidence suggests that it is necessary to take into account the individual characteristics of methotrexate pharmacokinetics, which are determined by the presence of polymorphisms of genes encoding methotrexate carrier proteins, to predict the risk of methotrexate-induced toxicity.&#x0D; Aims. The research aim is the assessment of associations of ABCB1 rs1045642 (3435CT) polymorphism with methotrexate safety for the patients with moderate and severe forms of psoriasis.&#x0D; Materials and methods. The study included 75 patients diagnosed with psoriasis treated with methotrexate during 21 day. Data on adverse drug reactions were collected using a clinically structured questionnaire, complete and biochemical blood tests, and urinalysis. The severity of adverse drug reactions was assessed using visual analog scales and the CTCAE toxicity scale. The severity of gastrointestinal ADR was assessed using the GSRS questionnaire. Genotyping was carried out by real-time PCR.&#x0D; Results. The gastrointestinal toxicity was detected in 38 patients (50.67%). The mean GSRS score was 7.97 9.18. Analysis of differences in the incidence of adverse drug reactions showed the presence of statistically significant differences in the frequency of adverse drug reactions in the gastrointestinal tract: the toxic effect of methotrexate was more often observed in carriers of the T allele of the ABCB1 rs1045642 polymorphism (3435CT), (CC 2 (14.3%), TC 18 (52.9%), TT 18 (66.7%), p = 0.006). Binomial regression demonstrated the presence of a statistically significant effect of the rs1045642 SNP polymorphism of the ABCB1 gene on the incidence of ADR from the gastrointestinal tract (OR = 8.64, p = 0.008).&#x0D; Conclusions. An association of ABCB1 rs1045642 SNP with the safety of gastrointestinal methotrexate therapy in patients with moderate and severe forms of psoriasis was revealed. The data obtained can be used to personalize the prescription of methotrexate to patients with psoriasis.

DNMT3B rs2424913 as a Risk Factor for Congenital Heart Defects in Down Syndrome

Impairments of the genes that encode enzymes that are involved in one-carbon metabolism because of the presence of gene polymorphisms can affect the methylation pattern. The altered methylation profiles of the genes involved in cardiogenesis may result in congenital heart defects (CHDs). The aim of this study was to investigate the association between the MTHFR rs1801133, MTHFR rs1801131, MTRR rs1801394, DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686, and DNMT3B rs2424913 gene polymorphisms and congenital heart defects in Down syndrome (DS) individuals. The study was conducted on 350 participants, including 134 DS individuals with CHDs (DSCHD+), 124 DS individuals without CHDs (DSCHD-), and 92 individuals with non-syndromic CHD. The genotyping was performed using the PCR-RFLP method. A statistically significant higher frequency of the DNMT3B rs2424913 TT in the DSCHD+ individuals was observed. The DNMT3B rs2424913 TT genotype, as well as the T allele, had significantly higher frequencies in the individuals with DS and atrial septal defects (ASDs) in comparison with the individuals with DS and other CHDs. Furthermore, our results indicate a statistically significant effect of the DNMT3B rs1569686 TT genotype in individuals with non-syndromic CHDs. The results of the study suggest that the DNMT3B rs2424913 TT genotypes may be a possible predisposing factor for CHDs in DS individuals, and especially those with ASDs.

TCF7L2, CASC8, and GREM1 polymorphism and colorectal cancer in south-eastern Romanian population.

Colorectal cancer (CRC) is a heterogeneous disease with an increasing trend and with multiple epigenetic alterations and different molecular features, a major cause of mortality and morbidity. The Wnt/β-Catenin pathway is involved in multiple aspects of cell dynamics, architecture of developing gastrointestinal tissues, and intestinal tissue homeostasis in adults, but its aberrant activity plays an important role in every aspect of colorectal carcinogenesis. The aim of our study was to investigate the association of the TCF7L2 rs7903146, CASC8 rs6983267, and Gremlin1 (GREM1) rs16969681 polymorphism in patients with CRC without other pathologies. A case-control study conducted on 31 patients diagnosed with CRC and 30 healthy controls age and sex-matched with the patients. Real time PCR was used to determine the genotypes of rs7903146, rs698267, rs1696981. We observed no association between rs6983267 and rs16969681 polymorphism and risk of CRC and low association between TCF7L2, rs7903146, polymorphism and risk of CRC. The recessive model of the TCF7L2 rs7903146 had an OR of 1.6 (95% CI 0.058-4.414, P < .05) which means that TT genotype increased the risk and possibility of development of CRC. Our study did not confirm a significant association between TCF7L2 rs7903146, CASC8 rs6983267, and GREM1 rs16969681 with CRC, but emphasizes the possibility of existence of a high risk of CRC development in patients with TT genotype of rs7903146.

The role of aldehyde dehydrogenase 2 in cardiovascular disease.

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme involved in the detoxification of alcohol-derived acetaldehyde and endogenous aldehydes. The inactivating ALDH2 rs671 polymorphism, present in up to 8% of the global population and in up to 50% of the East Asian population, is associated with increased risk of cardiovascular conditions such as coronary artery disease, alcohol-induced cardiac dysfunction, pulmonary arterial hypertension, heart failure and drug-induced cardiotoxicity. Although numerous studies have attributed an accumulation of aldehydes (secondary to alcohol consumption, ischaemia or elevated oxidative stress) to an increased risk of cardiovascular disease (CVD), this accumulation alone does not explain the emerging protective role of ALDH2 rs671 against ageing-related cardiac dysfunction and the development of aortic aneurysm or dissection. ALDH2 can also modulate risk factors associated with atherosclerosis, such as cholesterol biosynthesis and HDL biogenesis in hepatocytes and foam cell formation and efferocytosis in macrophages, via non-enzymatic pathways. In this Review, we summarize the basic biology and the clinical relevance of the enzymatic and non-enzymatic, tissue-specific roles of ALDH2 in CVD, and discuss the future directions in the research and development of therapeutic strategies targeting ALDH2. A thorough understanding of the complex roles of ALDH2 in CVD will improve the diagnosis, management and prognosis of patients with CVD whoharbour the ALDH2 rs671 polymorphism.