Rs2910164 Polymorphism Research Articles

MIR27A rs895819 CC Genotype Severely Reduces miR-27a Plasma Expression Levels.

Background/Objectives:MIR27A rs895819 polymorphism has emerged as a potential additional pharmacogenomic marker of fluoropyrimidine response. Current evidence on its potential effect on miR-27a expression, which represses DPD activity, leading to DPD deficiency and increased fluoropyrimidine-associated toxicity risk, is scarce and inconsistent. We have analyzed the effect of MIR27A rs895819 polymorphism on miR-27a-3p plasma expression levels under different models of inheritance to contribute further evidence on its plausible biological role in miR-27a expression. Methods: A total of 59 individuals with no medical history of cancer were included in this study. MIR27A rs895819 genotyping and miR-27a-3p expression were analyzed by using predesigned TaqMan assays. Results: The frequency of TT, TC, and CC genotypes was present at a prevalence of 50.8%, 44.1%, and 5.1%, respectively. Individuals carrying the CC genotype presented with decreased miR-27a-3p expression (0.422 fold-change versus TT, p = 0.041; 0.461 fold-change versus TC, p = 0.064), whereas no differences were present between TT and TC individuals (1.092 fold-change, p = 0.718). miR-27a-3p expression was decreased in CC individuals under a recessive model of inheritance (0.440 fold-change, p = 0.047). No differences were found in dominant (TT vs. TC+CC, 0.845 fold-change, p = 0.471) or over dominant (TT+CC vs. TC, 0.990 fold-change, p = 0.996) models of inheritance. Conclusions:MIR27A rs895819CC genotype leads to severely reduced miR-27a-3p expression in plasma. Further study of this association is warranted in cancer patients to apply MIR27A genotyping in therapeutics to identify fluoropyrimidine-treated patients who are at a decreased risk of experiencing fluoropyrimidine-induced severe toxicity.

The L-Arginine pathway may act as a mediator in the association between impaired one- carbon metabolism and hypertension.

Elevated fasting plasma total homocysteine (tHcy) and the methylenetetrahydrofolate reductase C677T polymorphism (rs1801133) have been associated with hypertension. Whether the L-Arginine pathway is involved, is unclear. We aimed to investigate whether the association between tHcy, the rs1801133 polymorphism and hypertension involves the L-Arginine pathway. THcy, plasma folate and cobalamin, erythrocyte glutathionine reductase activation coefficient, rs1801133 genotype, plasma L-Arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were determined in a cross-sectional study of 788 adults (aged 18 to 75), randomly selected from 2 town population registers. Participants participated in a medical checkup and provided a fasting blood sample. Associations between tHcy, rs1801133 genotype and L-Arginine pathway metabolites were assessed by multiple linear regression analysis and whether the tHcy and rs1801133 genotype are associated with hypertension via the L-Arginine pathway was investigated using mediation analysis. tHcy was positively associated with ADMA (B=0.003; SE=0.001; P<0.001) and SDMA (B=0.007; SE=0.002; P<0.001) and negatively associated with the L-Arginine/ADMA (B=-1.140; SE=0.451; P<0.05) and ADMA/SDMA (B=-0.006; SE=0.003; P<0.05) ratios. The MTHFR 677 CT vs CC genotype was negatively associated with ADMA (B=-0.013; SE=0.007; P<0.05) and with SDMA (B=-0.029; SE=0.013; P<0.05) in participants under 50 years. Each standard deviation increase (37.6) in the L-Arginine/ADMA ratio was associated with reduced hypertension risk (OR [95%CI], 0.6 [0.5, 0.8]). Mediation analysis showed that tHcy and ADMA were mediators in the association between the rs1801133 TT vs CC genotypes and hypertension. Our results support the L-Arginine pathway as a mediator in the association of impaired One-Carbon metabolism and hypertension.

Contribution of ERCC2 rs13181 (Lys751Gln) and rs1799793 (Asp312Asn) polymorphisms to the risk of bladder cancer in Bangladesh

BackgroundHuman Excision Repair Cross-Complementation Group 2 (ERCC2) proteins play a vital role in the nucleotide excision repair pathway through ATP-dependent helicase activity. Several studies found that polymorphisms in the ERCC2 gene are associated with susceptibility to different cancers, although the outcomes were confusing. ObjectiveAs a result, in this retrospective study, we investigated the relationship between genetic polymorphisms of the ERCC2 gene at codons 312 (rs1799793) and 751 (rs13181) and bladder cancer susceptibility in Bangladesh, as well as the disease's aggressiveness. MethodsGenetic polymorphisms of ERCC2 were assayed by the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method with 121 bladder cancer patients and 130 healthy controls. ResultsPatients who had the Gln/Gln polymorphism of ERCC2 at codon 751 (OR=3.27; 95% CI=1.19-8.67; p<0.05) and Asp/Asn at codon 312 (OR=2.14; 95% CI=1.03-4.29; p<0.05) were significantly associated with a higher risk of developing bladder cancer. Again, Gln/Gln polymorphisms in bladder cancer (p<0.05) were more likely to be present in individuals with cancer in the family. ConclusionsThis study reveals that susceptibility and bladder cancer aggressiveness are associated with polymorphisms at codon 751 and Asp/Asn at codon 312 of the ERCC2 gene.

The Relationship Between miR-196a2 Polymorphism and Colorectal Cancer Risk

ABSTRACT Objective MicroRNAs are small endogenous, non-coding, single-stranded posttranscriptional RNA molecules. The discovery of microRNAs has made new contributions to cancer diagnosis and treatment. These microRNAs reported as a responsible for colorectal cancer development with several epigenetic changes. In this study, it was aimed to evaluate the relationship between the polymorphism of miR-196a-2 polymorphism rs11614913 and colorectal cancer in Turkish population. Methods Two hundred colorectal cancer patient (124 colon cancer and 76 rectal cancer) and 240 health control individuals were included in our study, which was planned as a hospital based retrospective cohort study. MiR-196a2 polymorphism in peripheral blood samples has been determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method. Significance of the results has been evaluated by using SPSS (20.0 SPSS Inc., Chicago, IL, USA.) statistical program. Results miR-196a2 C / C + C / T genotypes was found to be associated with the risk of colorectal cancer development (p: 0.001; OR: 2.04, 95% CI: 1.293-3.236). The subgroup analysis, showed that the C / C + C / T genotype increased the risk of colon cancer development 2.11 times (p: 0.016; 95% CI: 1.136-3.918) and rectal cancer 2.86 times (p: 0.011; 95% CI:1.242-6.592). The relationship between any clinicopathological features of colorectal cancer and the frequency of the C / C + C / T genotype of miR196a2 was not statistically significant (p&gt; 0.05). Conclusion This study supports that miR-196a2's C / C + C / T genotypes is related with increased colorectal cancer development risk.

Influence of recipient KRAS gene rs712 polymorphisms on the overall survival rate of hepatocellular carcinoma after hepatic transplantation

Hepatocellular carcinoma (HCC) recurrence appears commonly after liver transplantation (LT), and it severely affected the long-term survival of patients. Previous studies have proved that Rap1A is involved in hepatocarcinogenesis and metastasis, and demonstrated the significant association between KRAS rs712 polymorphism and HCC. However, the relationship between KRAS rs712 polymorphism and HCC recurrence after LT remained unclear. A total of 93 HCC patients who underwent LT from March 2008 to Dec 2015 was analyzed. The genotypes of both donors and recipients had been confirmed as KRAS rs712. The independent risk factors that associated with HCC recurrence were investigated with univariate and multivariate logistic regression analysis. The recurrence-free (RFS) and overall survival (OS) were calculated with Cox regression analysis. The KRAS rs712 genotype frequencies were determined using the Χ2 test and the minor allele frequencies (MAFs) of KRAS rs712 genotypes were calculated by Hardy–Weinberg equilibrium. We found that the recipient KRAS rs712 polymorphism was significantly associated with HCC recurrence after LT. Moreover, the Milan criteria, microvascular invasion and recipient KRAS rs712 genotype were proved to be independent risk factors for HCC recurrence after LT. Patients with donor TG/TT genotypes had a significantly higher RFS and OS than TT genotype. The TNM stage, microvascular invasion, Milan criteria, treatment and recipient KRAS rs712 genotype were independent factors for the RFS of LT patients. Recipient KRAS rs712 polymorphism is associated with HCC recurrence after liver transplantation and plays as a promising bio-predictor of overall survival rate of HCC risks after hepatic transplantation.

Association between genetic variants (rs2839698, and rs217727) in lncRNA H19 and Acute lymphoblastic leukemia susceptibility: a case-control study in the Iranian population

Leukemia is a cancer affecting the hematopoietic system with an unclear pathogenesis. Recent studies suggest a correlation between several long non-coding RNAs (lncRNAs) and leukemia development. This study focuses on the potential link between H19 (rs2839698 and rs217727) polymorphisms and Acute Lymphoblastic Leukemia (ALL) susceptibility. The study involved 150 patients with clinically confirmed ALL and 150 controls. This research included 150 Iranian patients, who were confirmed to have clinical ALL, and 150 healthy people as the control group. A kit was utilized to extract the DNA of all the samples. After preparing the samples, DNA genotyping was done by using the tetra-primer ARMS-PCR method. After adjusting for age using multivariate logistic regression analysis, individuals carrying the CT genotype of rs2839698 were found to have a significantly 0.32-fold reduced risk of ALL compared with carriers of the CC genotype. Furthermore, a significant 0.48-fold reduction in ALL risk was observed in patients with CT+TT genotype rs2839698 compared with CC. Moreover, the over-dominant model was applied to compare the CT genotype of rs2839698 with its CC+TT genotype, which showed a significant 0.36-fold reduction of ALL risk. Notably, the cases of ALL and the control group were not significantly different in terms of their genotype and allele frequencies of rs217727 polymorphism. Yet, the TT haplotype was significantly associated with ALL risk (OR: 1.64, p = 0.025). Following the findings of this study, it can be concluded that H19 SNP rs2839698, rather than rs217727, might act as an innovative susceptibility marker for ALL leukemia.

Study of the Association between MTHFR Polymorphism (rs1801133) and the Outcome of Methotrexate Treatment in Rheumatoid Arthritis Patient

Abstract Background Rheumatoid arthritis is a chronic systemic autoimmune disease that causes loss of joint function and significantly reduces the quality of life. Methotrexate is one of the disease- modifying anti-rheumatic drugs that can influence treatment efficacy and toxicity. Methotrexate is used as an anchor drug for the treatment of rheumatoid arthritis and there may be differences in drug action between genotypes. Aim of the Work The present study was aimed to evaluate the impact of methylenetetrahydrofolate reductase (MTHFR) gene C677T (rs1801133) polymorphism on the clinical outcome of methotrexate treatment as regards treatment efficacy or toxicity in Egyptian rheumatoid arthritis patients. Subjects and Methods This study conducted on 45 patients diagnosed with rheumatoid arthritis receiving methotrexate as a first line of treatment. Subjects were classified into two groups; group I (responders, n = 25) and group II (non-Responders, n = 20) according to clinical response to methotrexate by using disease activity score (DAS28). Complete blood count, erythrocyte sedimentation rate, liver function, renal function, C- reactive protein, cyclic citrullinated peptide antibody and rheumatoid factor were done for all patients. Determination of methylenetetrahydrofolate reductase gene C677T (rs1801133) polymorphism was carried out using Real-time polymerase chain reaction. Results The present study did not confirm the presence of a significant association between the genotypic frequencies of the methylenetetrahydrofolate reductase gene C677T (rs1801133) polymorphism among the responders and the non-responders group in patients with rheumatoid arthritis. In addition, the methylenetetrahydrofolate reductase gene C677T (rs1801133) polymorphism did not show significant difference between disease complications among the responders and the non-responders groups. On the other hand, our findings suggested that a statistically significant difference was found between two groups of patients regarding disease activity score (DAS 28). Conclusion The current study revealed that there is no significant association between the genotypic frequencies of the methylenetetrahydrofolate reductase gene C677T (rs1801133) polymorphism among the responders and the non-responders groups of patients with rheumatoid arthritis. Moreover, the methylenetetrahydrofolate reductase gene C677T (rs1801133) polymorphism did not show significant difference between disease complications among the responders and the non-responders groups in patients with rheumatoid arthritis.

Association of miR-499 rs3746444, miR-149 rs2292832 polymorphisms and their expression levels with helicobacter pylori-related gastric diseases and Traditional Chinese Medicine syndromes.

To provide an objective experimental basis for the gastric mucosa pathological evolution and the transformation of different Traditional Chinese Medicine (TCM) syndromes in helicobacter pylori (H. pylori)-related gastric diseases (HPGD) patients, based on the combination of TCM syndrome differentiation, molecular biology and histopathology. A total of 203 participants were enrolled in this study. The expressions of miR-499/miR-149 and H. pylori infection in the gastric tissues from all participants were detected. The genotyping for miR-499 rs3746444 and miR-149 rs2292832 was performed. In H. pylori positive subjects, the proportion of precancerous gastric lesions (PGL) in liver-stomach disharmony syndrome (LSDS) group was higher than in spleen Qi deficiency syndrome (SQDS) group (P <0.001); The proportion of gastric cancer (GC) in SQDS group was higher than in spleen-stomach damp-heat syndrome (SSDHS) group and LSDS group (all P <0.001). We also found C allele of miR-149 rs2292832 was linked to lower risk of gastric atrophy [miR-149 rs2292832 C vs T: adjusted odds ratio = 0.207; 95% confidence interval (0.043-0.989); P = 0.048]. Compared with healthy control (HC) group, the expression of miR-499 was significantly increased in GC group, while the expression of miR-149 was significantly decreased in chronic inflammation group, PGL group and GC group (all P < 0.05). Test for trend showed that GC risk was on a rising trend with the increasing expression of miR-499 and decreasing expression of miR-149 (both P for trend < 0.05). The C allele of miR-149 rs2292832 may be a protective factor for gastric mucosal atrophy. H. pylori may participate in the evolution of benign to malignant gastric mucosa lesions by inducing the overexpression of miR-499 and down regulation of miR-149. In addition, patients with H. pylori infection combined SQDS or LSDS may have higher risk of gastric mucosal malignant lesions.

P88-2 The association of XRCC1 rs25487 polymorphism with luminal and non-luminal breast cancer subtype in Bali

P88-2 The association of XRCC1 rs25487 polymorphism with luminal and non-luminal breast cancer subtype in Bali

Association of rs401681 (C > T) and rs402710 (C > T) polymorphisms in the CLPTM1L region with risk of lung cancer: a systematic review and meta-analysis.

Although many genome-wide association studies (GWAS) have confirmed the negative associations between rs401681[T] / rs402710[T] in the Cleft lip and cleft palate transmembrane protein 1 (CLPTM1L) region and lung cancer (LC) susceptibility in Caucasian and Asian populations, some other studies haven't found these negative associations. The purpose of this study is to clarify the associations between them and LC, as well as the differences in these associations between patients of different ethnicities (Caucasians and Asians), LC subtypes and smoking status. Relevant literatures published before July 7, 2023 in PubMed, EMbase, Web of Science, MEDLINE were searched through the Internet. Statistical analysis of data was performed in Revman 5.3, including drawing forest plots, funnel plots and so on. Sensitivity and publication bias were performed in Stata 14.0. TSA software was performed for the trial sequential analysis (TSA) tests to assess the stability of the results. Registration number: CRD42023407890. A total of 41 literatures (containing 44 studies: 16 studies in Caucasians and 28 studies in Asians) were included in this meta-analysis, including 126476 LC patients and 191648 healthy controls. The results showed that the T allele variants of rs401681 and rs402710 were negatively associated with the risk of LC (rs401681[T]: [OR] = 0.87, 95% CI [0.86, 0.88]; rs402710[T]: [OR] = 0.88, 95% CI [0.86, 0.89]), and the negative associations were stronger in Caucasians than in Asians (Subgroup differences: I2 > 50%). In LC subtypes, the rs401681[T] was negatively associated with the risk of Non-small-cell lung carcinoma (NSCLC), Lung adenocarcinoma (LUAD) and Lung squamous cell carcinoma (LUSC) (P < 0.05), and these negative associations were stronger in Caucasians than in Asians (Subgroup differences: I2 > 50%). The rs402710[T] was negatively associated with the risk of NSCLC, LUAD and LUSC (P < 0.05), and these negative associations in Caucasians were the same as in Asians (Subgroup differences: I2 < 50%). The rs401681[T] was negatively associated with the risk of LC in both smokers and non-smokers (P < 0.05), and the negative association for smokers equals to that of non-smokers (Subgroup differences: P = 0.25, I2 = 24.2%). In LC subtypes, the rs401681[T] was negatively associated with the risks of NSCLC and LUAD in both Caucasian smokers and Asian non-smokers (P < 0.05). The rs402710[T] was negatively associated with the risk of LC in both smokers and non-smokers (P < 0.05), and there was no difference in the strength of this negative risk association between them in Caucasians (Subgroup differences: I2 = 0%). In Asians, this negative association was found to be predominantly among smokers ([OR] = 0.80, 95%CI [0.65, 0.99]). In LC subtypes, the rs402710[T]was negatively associated with the risk of NSCLC in non-smokers, and this negative association was found to be predominantly among non-smokers in Asians ([OR] = 0.75, 95%CI [0.60, 0.94]). The T allele variants of rs401681 and rs402710 are both negatively associated with the risk of developing LC, NSCLC (LUAD, LUSC) in the Caucasian and Asian populations, and the negative associations with the risk of LC are higher in Caucasians. Smoking is an important risk factor for inducing the rs401681 and rs402710 variants and causes LC development in both populations. Other factors like non-smoking are mainly responsible for inducing the development of NSCLC in Asians, and is concentrated in LUAD among Asian non-smoking women.

TP53 Gene Polymorphism (Rs1042522) in Rheumatoid Arthritis and Systemic Lupus Erythematosus: An Updated Systematic Review and Meta-Analysis.

The p53 protein has important roles in apoptosis, proliferation, and prevention of DNA damage. Several studies have reported that TP53 gene polymorphism is associated with various autoimmune diseases, including Rheumatoid arthritis (RA) and Systemic lupus erythematosus (SLE). Evaluation of the correlation between TP53 gene rs1042522 polymorphism and RA and SLE risk by meta-analysis. Databases, including PubMed and Scopus, were searched to find studies assessing the association between TP53 gene polymorphism and RA and SLE risk in different populations up to August 2022. The protocol of this article was registered on the International Prospective Register Of Systematic Reviews (PROSPERO number: CRD42022309655). Herein, 7 case-control studies, including 2498 cases and 3799 controls in the SLE group, and 6 case-control studies comprising 1593 cases and 4460 controls in the RA group that investigated rs1042522 SNP were included in the meta-analysis. Herein, CG genotypes were more frequent in healthy participants compared to SLE patients and may associated with a decreased SLE risk (OR=0.85, CI: 0.76-0.95, P-value <0.006). Besides, dominant and recessive models of CC+ CG vs. GG were also protective for SLE risk (OR=0.85, CI: 0.76-0.95, P-value <0.004). In summary, this study discloses a weak correlation between rs1042522 and a decreased risk of SLE. However, no significant association was found in RA.

Association of MnSOD, CAT, and GPx1 Gene Polymorphism with Risk of Diabetic Nephropathy in South Indian Patients: A Case-Control Study.

Diabetic nephropathy (DN) is one of the common complications of type 2 diabetes mellitus (T2DM), and oxidative stress plays a key role in the pathogenesis of DN. Studies have demonstrated that antioxidants (MnSOD, CAT, and GPx1) may reduce the complications associated with T2DM. The purpose of the study is to correlate the role of antioxidant gene polymorphisms in the pathogenesis of DN among T2DM individuals in the South Indian population. It clarifies the importance of early manifestation and reliable genetic indicators modulating the oxidative stress mechanism in DN.The study participants were divided and grouped as Group 1: Control, Group 2: T2DM without DN, and Group 3: T2DM with DN (n = 100 in each group). The levels of plasma glucose, HbA1c, renal profile, SOD, CAT, GPx1, MDA, and TAS were assessed. MnSOD (rs4880), CAT (rs1049982), and GPx1 (rs1050450) polymorphisms were genotyped via Tetra-arms PCR.The genotypes of GPx1 depict a significant role in the progression of DN in T2DM patients (co-dominant [OR: 2.134; 95% CI (1.202-3.788), p < 0.01], dominant [OR: 2.015; 95% CI (1.117-3.634), p = 0.02], and recessive model [OR: 2.215; 95% CI (1.235-3.972), p = 0.008]); whereas rs4880 and rs1049982 polymorphisms are not associated with DN progression. As a result, GPx1 (rs1050450) polymorphism could be a diagnostic risk factor for developing DN in T2DM patients. Moreover, the genotypes of rs4880 and rs1049982 polymorphism show significant difference in the antioxidant parameters compared to the genotypes of rs1050450.In contradiction to earlier studies, the current study demonstrates that the genotypes of rs1050450 (GPx1) can be considered as an influential component for higher susceptibility and risk of developing DN in T2DM patients among the South Indian population.

The Impact of Cardiovascular Disease Gene Polymorphism and Interaction with Homocysteine on Deep Vein Thrombosis.

Deep vein thrombosis (DVT) affects vascular health and can even threaten life; however, its pathogenesis remains unclear. Cardiovascular disease (CVD) and DVT share common risk factors, such as dyslipidemia, aging, etc. We aimed to investigate the loci of published CVD susceptibility genes and their association with environmental factors that might be related to DVT. Genotyping by Kompetitive Allele Specific PCR (KASP), collection of lifestyle information, and determination of blood biochemical markers were performed in 165 DVT cases and 164 controls. The impact of six single nucleotide polymorphisms (SNPs) and additional potential variables on DVT morbidity was evaluated using unconditional logistic regression (ULR). To explore the high-order interactions related to genetics and the body's internal environment exposure that affect DVT, ULR, crossover analysis, and multifactor dimensionality reduction/generalized multifactor dimensionality reduction (MDR/GMDR) were employed. Sensitivity analyses were performed using the EpiR package. The polymorphisms of FGB rs1800790 and PLAT rs2020918 were significantly associated with DVT. The optimum GMDR interaction model for gene-gene (G × G) consisted of THBD rs1042579, PLAT rs2020918, and PON1 rs662. The PLAT rs2020918 and MTHFR rs1801133 polymorphisms together eliminated the maximum entropy by the MDR method. The optimum GMDR interaction model for gene-environment (G × E) consisted of MTHFR rs1801133, FGB rs1800790, PLAT rs2020918, PON1 rs662, and total homocysteine (tHcy). Those with high tHcy levels and three risk genotypes significantly increased the DVT risk. In conclusion, certain CVD-related SNPs and their interactions with tHcy may contribute to DVT. These have implications for investigating DVT etiology and developing preventive treatment plans.

Association between Mir-499, Mir-27a, and Mir-146a polymorphisms and their susceptibility to recurrent spontaneous abortion; in silico analysis.

Recurrent spontaneous abortion (RSA) is defined as two or more pregnancy losses before 24 gestational weeks, accounting for 1-3% of fertile couples. A vast majority of single-nucleotide polymorphisms (SNPs) in some microRNA (miRNA) genes can change the miRNA-mRNA interaction and are associated with the risk of RSA. This study was designed to better elucidate the association between miR-27a, miR-499, and miR-146a polymorphisms and RSA risk. SNP genotyping of miR-27a (rs895819), miR-499 (rs3746444), and miR-146a (rs2910164) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and tetra amplification-refractory mutation system PCR in 98 patients with RSA and 105 healthy subjects. Our results showed that the miR-499 rs3746444 and miR-27a rs895819 polymorphisms were significantly associated with RSA risk, whereas no significant differences were observed between the rs2910164 polymorphism and RSA susceptibility. We proposed that the miR-499 rs3746444 and miR-27a rs895819 polymorphisms were correlated with RSA in our population, but the miR-146a rs2910164 variant was not associated with the risk of RSA.

The role of ALDH2 rs671 polymorphism and C-reactive protein in the phenotypes of male ALS patients.

The aldehyde dehydrogenase 2 (ALDH2) rs671 (A) allele has been implicated in neurodegeneration, potentially through oxidative and inflammatory pathways. The study aims to investigate the effects of the ALDH2 rs671 (A) allele and high sensitivity C-reactive protein (hs-CRP) on the clinical phenotypes of amyotrophic lateral sclerosis (ALS) in male and female patients. Clinical data and ALDH2 rs671 genotype of 143 ALS patients, including 85 males and 58 females, were collected from January 2018 to December 2022. All patients underwent assessment using the Chinese version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Complete blood count and metabolic profiles were measured. Clinical and laboratory parameters were compared between carriers and non-carriers of the rs671 (A) allele in males and females, respectively. The significant parameters and rs671 (A) Allele were included in multivariate linear regression models to identify potential contributors to motor and cognitive impairment. Mediation analysis was employed to evaluate any mediation effects. Male patients carrying rs671 (A) allele exhibited higher levels of hs-CRP than non-carriers (1.70 mg/L vs. 0.50 mg/L, p = 0.006). The rs671 (A) allele was identified as an independent risk factor for faster disease progression only in male patients (β = 0.274, 95% CI = 0.048-0.499, p = 0.018). The effect of the rs671 (A) allele on the executive function in male patients was fully mediated by hs-CRP (Indirect effect = -1.790, 95% CI = -4.555--0.225). No effects of the rs671 (A) allele or hs-CRP were observed in female ALS patients. The effects of the ALDH2 rs671 (A) allele and the mediating role of hs-CRP in male patients remained significant in the sensitivity analyses. The ALDH2 rs671 (A) allele contributed to faster disease progression and hs-CRP mediated cognitive impairment in male ALS patients.

Genetic polymorphisms in FABP2, CYP2E1, and TP53 genes are potentially associated with colorectal cancer susceptibility

Colorectal cancer (CRC) is among the most prevalent cancers with a high mortality rate. Both genetic and environmental factors contribute to CRC development. This study aimed to assess the association of single nucleotide polymorphisms (SNPs) in the fatty acid binding protein-2 (rs1799883), Cytochrome P450 2E1 (rs3813865), TP53 (rs1042522), and Murine double minute 2 (rs1042522) genes with CRC. A cross-sectional case–control study was conducted at the Institute of Molecular Biology and Biotechnology from May 2020 to March 2021, involving CRC patients (N = 100) and controls (N = 100) recruited from the Multan district in Pakistan. Polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) and tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) were employed to investigate the studied SNPs. The association of SNPs in all genes with CRC was examined either individually or in various combinations. Genotypes at three SNPs, rs1799883 in FABP2, rs3813865 in CYP2E1, and rs1042522 in TP53, were found to be associated with the development of CRC, while rs1042522 in MDM2 was not. Patients who were married, smoked, lacked exercise habits or had a family history of CRC were at a greater risk of acquiring the disease. FABP2 gene rs1799883, CYP2E1 gene rs3813865, and TP53 gene rs1042522 polymorphisms are significant in the development of CRC in Pakistani participants.

Exploring Genetic Variants and Platinum Chemotherapy Response in Indonesian Non-Small Cell Lung Cancer Patients: Insights from ERCC2 rs13181.

Individual responses to platinum-based treatment for Non-Small Cell Lung Cancer (NSCLC) are influenced by genetic polymorphisms, including Single Nucleotide Polymorphisms (SNPs). This study aimed to explore the role of ERCC2 in the Nucleotide Excision Repair (NER) pathway for platinum-based chemotherapy in NSCLC. While ERCC2 is widely studied, data for Southeast Asian populations are lacking. Addressing this gap could improve personalized treatment strategies for NSCLC in this demographic. This study recruited 82 NSCLC patients with wildtype mutations of EGFR at Dr. H.A. Rotinsulu Lung Hospital, Bandung, and Dharmais Cancer Hospital, Jakarta. Data were collected prospectively from whole blood samples and medical records, while the effectiveness of chemotherapy was assessed by evaluating the response using RECIST 1.1 criteria on fourth cycle of chemotherapy. The results of this study showed the presence of genotype variation among the subjects, with frequency distribution as follows: AA genotype (82.9%), AC genotype (15.9%), and CC genotype (1.2%). The analysis of the association between ERCC2 rs13181 CC + AC versus AA with RECIST 1.1 yielded an odds ratio (OR) of 1.042 (95% CI: 0.292-3.715; p=0.950). A multivariate analysis that included cancer stage and chemotherapy regimen as additional variables produced an adjusted odds ratio (aOR) of 0.970 (95% CI: 0.263-3.568; p=0.963). This study did not find statistically significant associations between ERCC2 rs13181 polymorphisms and chemotherapy responses. However, this research highlights the presence of genetic variation within the Indonesian population, with the AA genotype being the most prevalent, which may influence chemotherapy responses. The results provided preliminary data and lay the foundation for future comprehensive cohort observational investigations.

ALDH2 deficiency augments atherosclerosis through the USP14-cGAS-dependent polarization of proinflammatory macrophages

The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism commonly exists in the East Asian populations and is associated with high risks of cardiovascular disease (CVD). However, the cellular and molecular mechanisms that underlie the ALDH2 rs671 mutant-linked high CVD remain elusive. Here, we show that macrophages derived from human ALDH2 rs671 carriers and ALDH2 knockout mice exhibited an enhanced pro-inflammatory macrophage phenotype and an impaired anti-inflammatory macrophage phenotype. Transplanting bone marrow from ALDH2−/−ApoE−/− to ApoE−/− mice significantly increased atherosclerotic plaque growth and pro-inflammatory macrophage polarization in vivo. Mechanistically, ALDH2 inhibited activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in macrophages. Pharmacological inhibition of cGAS by RU.521 completely neutralized ALDH2-deficiency-induced macrophage polarization. In-depth mechanistic investigation showed that ALDH2 accelerated cGAS K48-linked polyubiquitination degradation at lysine 282 in macrophages by reducing the interaction between ubiquitin-specific protease 14 (USP14) and cGAS, mainly through its enzymatic role in mitigating 4-hydroxy-2-nonenal (4-HNE) accumulation. Consistently, USP14 knockdown in bone marrow cells alleviated proinflammatory responses in macrophages and protected against atherosclerosis. Our findings provide new mechanistic insights of ALDH2 deficiency-associated proinflammation and atherosclerosis and new therapeutic and preventive paradigms for treatment of atherosclerosis-associated CVD.

MiR-146a (rs2910164) Gene Polymorphism and Its Impact on Circulating MiR-146a Levels in Patients with Inflammatory Bowel Diseases.

MicroRNA-146a (miR-146a) has been involved in the pathophysiology of inflammatory bowel disease (IBD). However, the precise processes are still not entirely understood. Contradictory studies suggest that miR-146a expression could be influenced by the miR-146a rs2910164 C > G polymorphism. This case-control study aimed to investigate the association ofmiR-146a rs2910164 C > G gene polymorphism and its impact on circulating miR-146a expression levels in Egyptian IBD patients. We included 40 IBD patients and 30 matched healthy controls. Genotyping of miR-146a rs2910164 polymorphism and assessment of miR-146a expression level were done using quantitative real-time PCR in all participants. MiR-146a rs2910164 GG genotype and the G allele were reported in 47% and 70% of the IBD patient group, respectively. And they were associated with increased IBD risk. All the IBD patients with the CC genotype (100%) and most of those with the CG genotype (66.67%) had an inactive disease, while most IBD patients with the GG genotype (73.68%) had an active disease. The miR-146a expression level was the highest with the CC genotype and the lowest with the GG genotype. Also, miR-146a expression level decreased significantly in IBD patients than controls and with disease activity. Combined detection of fecal calprotectin with miR-146a expression level improved the diagnostic sensitivity and the negative predictive value in differentiating IBD patients with active disease from those inactive.Our study identified a strong association of miR-146a rs2910164 GG genotype and G allele with IBD-increased susceptibility and activity in the Egyptian population. The miR-146a rs2910164 polymorphism can reduce miR-146a expression levels in these patients as well. Further research on a larger sample size and different ethnic populations can be the key to progress in establishing this genetic association.

Impaired Cholesterol Efflux Capacity rather than Low HDL-C Reflects Oxidative Stress under Acute Myocardial Infarction.

Acute myocardial infarction (AMI) causes irreversible damage to cardiomyocytes due to the discontinuation of oxygen supply and leads to systemic oxidative stress. It has been reported that high-density lipoprotein (HDL) particles have antioxidant capacity, and reduced antioxidant capacity is associated with decreased cholesterol efflux capacity (CEC). The purpose of this study was to clarify the usefulness of CEC measurement in patients with AMI. We investigated the association between CEC and oxidative stress status in a case-control study. This study included 193 AMI cases and 445 age- and sex-matched controls. We examined the associations of CEC with HDL-cholesterol (HDL-C) and oxidized human serum albumin (HSA), an index of systemic oxidative stress status, and the effect of aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which has been reported to affect HDL-C level and risk for MI, on these associations. Both bivariable and multivariable analyses showed that CEC was positively correlated with HDL-C levels in both AMI cases and controls, with a weaker correlation in AMI cases than in controls. In AMI cases, oxidized HSA levels were associated with CEC in both bivariable and multivariable analyses, but not with HDL-C. These associations did not differ among the ALDH2 genotypes. CEC, but not HDL-C level, reflects systemic oxidative stress status in patients with AMI. CEC measurement for patients with AMI may be useful in that it provides information on systemic oxidative stress status as well as atherosclerosis risk.