Rs2910164 Polymorphism Research Articles

Association of TP53 polymorphisms with the acquisition of EGFR T790M mutations in patients with first- or second-generation EGFR-TIK progression.

e20560 Background: Lung cancer is the leading cause of cancer death worldwide. EGFR tyrosine kinase inhibitors (TKIs) has transformed management in those patients. However, the majority of patients will become resistant to EGFR-TKIs after a period of time. The T790M acquired mutation in exon 20 of the EGFR is the predominant molecular mechanism of acquired resistance. In first-line treatment of global patients with NSCLC, osimertinib had better efficacy compared to first-generation TKIs. In the FLAURA study, the median PFS with first-line osimertinib in Asians was only 16.5 months, compared to 18.6 months in the global population. Moreover, the OS benefit in the Asian population was relatively small. At the same time, the mechanism of resistance to osimertinib is very complex and patients have limited treatment options after first-line osimertinib resistance. A variety of factors can influence the decision for first-line treatment in EGFR mutation-positive patients, including follow-up regimens, the presence of brain metastases, and tolerability, all of which should be considered in the long-term treatment plan. Knowing in advance whether patients are likely to acquire EGFR T790M mutations will help in making treatment decisions. Previous studies have shown that TP53 Arg72Pro polymorphism (rs1042522) is associated with the risk and prognosis of lung cancer. Currently, the association between EGFR mutations and TP53 polymorphisms is unclear, but previous reports have suggested that patients with EGFRmutation demonstrated a higher rate of TP53 mutation than EGFR wild type patients. Therefore, this study aim to explore the association of TP53 polymorphisms (rs1042522) with EGFR T790M acquired mutations, considering the value of T790M in lung cancer treatment. Methods: We analyzed two independent cohorts of patients with EGFR-mutant NSCLC who progressed after first-line EGFR-TKIs treatment from 2013 to 2021 (cohort 1: n=108; cohort 2: n=148). All patients were tested with plasma next-generation sequencing (NGS). Results: The acquired T790M mutation rate was 36%, 30% and 43% in all patients (n = 256), cohort 1 and cohort 2, respectively. Logistic regression analysis showed that TP53 rs1042522 polymorphism was significantly associated with an increased risk of T790M acquired mutation in cohort 1 (GG versus CC: OR (95% CI) = 3.57 (1.15-12.2), P = 0.033) and cohort 2 (GG versus CC: univariable OR (95% CI) = 3.53 (1.30-10.3), P = 0.016; multivariable OR (95% CI) = 2.94 (1.04-8.87), P= 0.047). Conclusions: We found that the TP53 rs1042522 polymorphism GG was associated with EGFR T790M acquired mutations. Knowing in advance whether patients are likely to acquire EGFR T790M mutations will help in making treatment decisions.

Emerging insights into the relationship between pre-microRNA146a rs2910164 gene polymorphism and TNF-α in ischemic stroke

Abstract Objectives This study investigated the association between the pre-miRNA146a C>G rs2910164 polymorphism and serum TNF-α in Egyptian patients with IS. Methods A case-control study was conducted on 75 Egyptian cases with IS and 75 sex-matched control subjects aged 57–65 years. Genomic DNA analysis of pre-miRNA146a and TNF-α measurement was performed with real-time PCR and ELISA, respectively. Results There was a statistically significant difference between cases of ischemic stroke (IS) and control subjects in pre-miRNA146a rs2910164 GG genotype (p=0.017) and G allele (p=0.005). The pre-miRNA146a rs2910164 is significantly associated with large artery atherosclerosis [LAA] in GG genotypes (p=0.019) and G alleles (p=0.004) compared to control subjects. There was a highly statistically significant increase in TNF-α levels (p<0.001) in IS compared to the control group. There was also a statistically significant increase in TNF-α levels (p=0.001) in GG genotypes in IS. Conclusions Our results showed that there was a statistically significant association between pre-miRNA146a rs2910164 GG genotype and susceptibility to IS and LAA. In addition, there was a statistically significant association between pre-miRNA146a rs2910164 GG genotype and TNF-α in IS subjects.

Association between miR-146a rs2910164, miR-196a2 rs11614913, and miR-499 rs3746444 polymorphisms and the risk of esophageal carcinoma: A case-control study.

MicroRNAs (miRNAs) are a group of small, non-coding, and endogenous RNAs that regulate gene expression and over 50% of them are located at cancer-related genomic regions or fragile sites. According to previous studies there is significant association of miRNA single nucleotide polymorphisms (SNPs) with tumorigenesis (e.g., esophageal cancer, hepatocellular cancer, gastric cancer, bladder cancer, breast cancer, lung cancer, and colon cancer), however, the conclusions have been inconsistent. To investigate the relationship between miR-146a rs2910164 C > G, miR-196a2 rs11614913 T > C, and miR-499 rs3746444 A > G polymorphisms and the susceptibility to esophageal squamous cell cancer (ESCC) in the Chinese Han nationality, we recruited 829 cases and 1522 controls in our study. In this case-control study, our results suggest that the rs3746444 GG genotype increased ESCC risk [homozygote model: adjusted odds ratio (OR), 2.26; 95% CI, 1.33-3.83; p=0.003, recessive model: adjusted OR, 2.34; 95% CI, 1.38-3.96; p=0.002], which remained consistent after Bonferroni correction. There was no association of rs11614913 and rs2910164 polymorphisms with ESCC. After adjusting by age, sex, smoking, and drinking status and body mass index (BMI), the multiple logistic analysis suggested that rs11614913 T → C variation reduced ESCC susceptibility in females and in the ≥63 years old subgroups, while rs2910164 C → G variation increased ESCC risk in both two BMI subgroups.

Associations of MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) Polymorphisms with Susceptibility to Bladder Cancer: A Systematic Review and Meta-Analysis.

The effects of the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms on bladder cancer risk have been evaluated in some studies. However, the results were conflicting and ambiguous. Therefore, we aimed to perform a comprehensive meta-analysis to investigate the association of these polymorphisms with risk of bladder cancer from all eligible case-control studies. PubMed, Web of science, Scopus, SID, CNKI and SciELO databases were searched to identify all relevant studies published up to 1 January, 2021. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. A total of 20 case-control studies including 11 studies with 3463 cases and 3927 controls on MTHFR rs1801133 (677C>T) and 9 studies with 3177 cases and 3502 controls on rs180113 (1298A>C) polymorphism were selected. Pooled data revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were not associated with risk bladder cancer in overall. Stratified analysis by ethnicity revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were associated with bladder cancer risk in Asians, but not in Caucasians. There was no publication bias. The current meta-analysis revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were not risk factor for development of bladder cancer globally. However, large sample size, well-designed, and population-based studies should be performed to verify the association of the MTHFR polymorphisms with bladder cancer risk.

Association between miR-196a-2 Gene Polymorphism and Ovarian Cancer Prognosis in Egyptian Females.

Background:Ovarian cancer is the fifth leading cause of cancer-related deaths among women worldwide. Unfortunately, early detection tests are relatively lacking. Diagnosis in the late stages of the disease carries a poor prognosis. Objective:To evaluate the relationship between miR-196a-2 rs11614913 polymorphism and ovarian cancer risk and prognosis in Egyptian females. Methods: In this case-control study, the participants were classified into 2 groups. Group A is the control group which included 50 healthy females. Group B included 50 patients newly diagnosed with ovarian carcinoma confirmed by histopathological analysis. Immunohistochemistry for P53 and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for miR-196a-2 genotypes detection were performed. Results:There was a statistically significant difference among ovarian cancer cases and controls regarding genotypes (P = 0.003). However, the distribution of the T and C alleles in both studied groups showed no significant difference (P = 0.17). There was a statistically significant increase of CA 125 levels among CT and CC genotypes carriers of ovarian cancer cases (p = 0.04). Besides, there was a statistically significant correlation between miR-196a-2 polymorphism and each of tumor grade (P <0.001), p53 immunohistochemical expression (P= 0.002), and Figo classification (P <0.001). Conclusion:There was a statistically significant increase of CA 125 levels among C allele carriers of ovarian cancer cases. Besides, there was a statistically significant association between the miR-196a-2 polymorphism and each of tumor grade, p53 immunohistochemical expression, and Figo classification. So, miR-196a-2 polymorphism can be a possible prognostic factor in ovarian cancer.

Associations between TERT Promoter Mutations and Survival in Superficial Spreading and Nodular Melanomas in a Large Prospective Patient Cohort

Survival outcomes in melanoma and their association with mutations in the telomerase reverse transcriptase gene TERT promoter remain uncertain. In addition, few studies have examined whether these associations are affected by a nearby common germline polymorphism or vary on the basis of melanoma histopathological subtype. We analyzed 408 primary tumors from a prospective melanoma cohort for somatic TERT-124[C>T] and TERT-146[C>T] mutations, the germline polymorphism rs2853669, and BRAFV600 and NRASQ61 mutations. We tested the associations between these variants and clinicopathologic factors and survival outcomes. TERT-124[C>T] wasassociated with thicker tumors, ulceration, mitoses (>0/mm2), nodular histotype, and CNS involvement. In a multivariable model controlling for the American Joint Committee on Cancer stage, TERT-124[C>T] was an independent predictor of shorter recurrence-free survival (hazard ratio= 2.58, P= 0.001) and overall survival (hazard ratio= 2.47, P= 0.029). Patients with the germline variant and TERT-124[C>T]-mutant melanomas had significantly shorter recurrence-free survival than those lacking either or both sequence variants (P < 0.04). The impact of the germline variant appeared to be more pronounced in superficial spreading than in nodular melanoma. No associations were found between survival and TERT-146[C>T], BRAF, or NRAS mutations. These findings strongly suggest that TERT-124[C>T] mutation is a biomarker of aggressive primary melanomas, an effect that may be modulated by rs2853669.

Analysis of polymorphic variants of the survivin promoter and p53 transcription factor in patients with genital endometriosis, type 1 diabetes mellitus and their combination

AIM: The aim of this study was to analyze the association between the SNP surviving, the p53 gene polymorphisms and the risk of developing genital endometriosis and type 1 diabetes mellitus.&#x0D; MATERIALS AND METHODS: The frequency of allelic variants of the BIRC5 and TP53 genes was studied by PCR-RFLP analysis in 243 women, including 84 patients with genital endometriosis (stages IIV), 85 patients with type 1 diabetes mellitus, 47 women with diabetes mellitus type 1 and endometriosis and 27 women of the control group represented by the population sample.&#x0D; RESULTS: It was found that the frequency of the allele C polymorphic variant of rs9904341 in the BIRC5 gene was significantly higher in the group of patients with diseases compared to the population sample (p 0.05). Significant differences for the C / C genotype in patients with genital endometriosis relative to the control group (p = 0.01) According to the odds ratio, the risk of developing genital endometriosis was 56 times higher for this genotype (ОR 56.31, CI 2.521258.7). Significant differences for the ins/ins genotype of TP53(p16) gene in patients with genital endometriosis relative to the control group (p = 0.005). According to the odds ratio, the risk of developing genital endometriosis was 94 times higher for this genotype (ОR 94.29, CI 3.882288.81). In addition, the frequency of the allele ins polymorphic variant of p16 in the TP53 gene was significantly higher in the group of patients with diseases compared to the control group (p 0.05). The same results for the P allele of the rs1042522 polymorphism in the TP53 gene (p 0.05). According to the odds ratio, the risk of developing genital endometriosis with diabetes mellitus type 1 was 3 times higher for G/A genotype of rs9930232 (p6) than for other genotypes (ОR 3.1, CI 2.521258.7)&#x0D; CONCLUSIONS: The investigated factors can be considered as risk markers for the development of genital endometriosis and diabetes mellitus type one.

Association between Genetic Polymorphism of GSTP1 and Toxicities in Patients Receiving Platinum-Based Chemotherapy: A Systematic Review and Meta-Analysis.

Platinum-based chemotherapy regimens have been proven to be effective in various cancers; however, considerable toxicities may develop and can even lead to treatment discontinuation. Diverse factors may influence adverse treatment events, with pharmacogenetic variations being one prime example. Polymorphisms within the glutathione S-transferase pi 1 (GSTP1) gene may especially alter enzyme activity and, consequently, various toxicities in patients receiving platinum-based chemotherapy. Due to a lack of consistency in the degree of elevated complication risk, we performed a systematic literature review and meta-analysis to determine the level of platinum-associated toxicity in patients with the GSTP1 rs1695 polymorphism. We conducted a systematic search for eligible studies published before January 2022 from PubMed, Web of Science, and EMBASE based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between the rs1695 polymorphism and various toxicities. Ten eligible studies met the inclusion criteria. The pooled ORs for hematological toxicity and neutropenia in the patients with the variant (G) allele were 1.7- and 2.6-times higher than those with the AA genotype (95% CI 1.06–2.73 and 1.07–6.35), respectively. In contrast, the rs1695 polymorphism resulted in a 44% reduced gastrointestinal toxicity compared to wild-type homozygotes. Our study found that the GSTP1 rs1695 polymorphism was significantly correlated with platinum-induced toxicities. The study also revealed that rs1695 expression exhibited tissue-specific patterns and thus yielded opposite effects in different tissues. A personalized chemotherapy treatment based on these polymorphisms may be considered for cancer patients in the future.

Association between Genetic Polymorphisms in MicroRNAs 196a2 (rs11614913) and 34 b/c (rs4938723) and Risk of Hepatocellular Carcinoma in Egyptian Patients.

Background:Hepatocellular carcinoma (HCC) is a common cancer with substantial cancer-related deaths worldwide. Deregulation of some genetic polymorphisms has been identified in HCC. Objective:We aimed to demonstrate the frequency of miRNA 196a2 rs11614913 and miRNA 34 b/c rs4938723 gene polymorphisms in HCC patients and their correlation with the clinical features and laboratory findings at diagnosis. Subjects and methods:The study was performed on 40 patients with newly diagnosed HCC and 40 patients with liver cirrhosis in addition to 40 age and sex-matched healthy controls. Detection of miRNA 196a2 rs11614913 and miRNA 34 b/c rs4938723 gene polymorphisms was determined by PCR-RFLP. Results:HCC patients had significantly higher frequency of miR-196-2a rs11614913 CC genotype when compared with cirrhotic patients (60.0 % versus 30.0 %, p=0.013). In spite of the fact that HCC patients also had higher frequency of miR-196-2a rs11614913 CC genotype in comparison to controls, the difference fell short of statistical significance (60.0 % versus 42.5 %, p=0.18). No significant differences were found between the studied groups regarding the frequency of miR-196-2a alleles. miR34 b/c rs4938723 CC genotype was the only identified genotype in all participants in the three studied groups. No significant associations were found between the different clinical and laboratory variables and genotypic variations in HCC patients. Conclusions:This study identified miR-196a2 rs11614913 CC genotype as a risk factor for HCC development while we failed to document similar relation for miR-34b/c rs4938723 polymorphism.

ALDH2 Polymorphism rs671 *1/*2 Genotype is a Risk Factor for the Development of Alcoholic Liver Cirrhosis in Hakka Alcoholics.

BackgroundAlcoholics are prone to alcoholic cirrhosis (ALC). Aldehyde dehydrogenase 2 (ALDH2) is involved in alcohol metabolism. Herein, the relationship between ALDH2 genotypes and ALC was analyzed among Hakka alcoholics in southern China.MethodsA total of 213 alcoholics and 214 non-alcoholics were included in the study. The ALDH2 gene rs671 polymorphism was analyzed, life history, disease history, and auxiliary examination results of these participants were collected.ResultsThe alcoholics had higher level of total serum protein, and serum globulin, lower level of serum albumin, serum albumin/globulin ratio, serum prealbumin, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) than non-alcoholics. In the 213 alcoholics, 180 developed ALC. There were 206 non-ALC persons in the 214 non-alcoholics. The proportion of the ALDH2 rs671 G/G homozygous (*1/*1) was significantly lower in ALC patients (83.3%) than that of other groups (100.0% in non-ALC in alcoholics, 95.6% in non-ALC in non-alcoholics), while the proportion of the G/A heterozygous (*1/*2) was significantly higher in ALC patients (16.7%) than that of other groups (0% in non-ALC in alcoholics, 4.4% in non-ALC in non-alcoholics). Logistic regression analysis indicated that participants with low level of NLR (adjusted OR 5.543, 95% CI 2.964–10.368, P<0.001), LMR (adjusted OR 9.256, 95% CI 4.740–18.076, P<0.001), and PLR (adjusted OR 6.047, 95% CI 3.372–10.845, P<0.001), and ALDH2 G/A genotype (adjusted OR 6.323, 95% CI 2.477–16.140, P<0.001) had a significantly higher risk of ALC.ConclusionALDH2 polymorphism rs671 *1/*2 genotype is a potential risk factor for the development of ALC among Hakka alcoholics.

Association between miRNA-499 gene polymorphism and autoimmune diseases: A meta-analysis.

IntroductionThe association between miRNA-499 rs3746444 and a variety of autoimmune diseases has been reported. However, these results were contradictory and just focused on one or two autoimmune diseases. The present study aims to examine the possible association between rs3746444 polymorphism and the risk of autoimmune diseases.MethodsThe studies that evaluated the association between miRNA-499 gene polymorphism and autoimmune diseases were retrieved. Five different genetic models were used to evaluate the association. The random-effects model was used to pool the effect sizes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the associations. Stratification analyses were performed by ethnicity and type of autoimmune diseases. False-positive report probability (FPRP) was performed for determining noteworthy associations.ResultsSeventeen articles (twenty studies) involving 4,376 cases and 4,991 controls were identified and included in our meta-analysis. The pooled ORs of all eligible case-control studies indicated a significant association between miRNA-499 gene polymorphism and autoimmune diseases: (T vs. C: OR = 0.877; 95% CI: 0.774, 0.993; P = 0.039). Stratified analysis indicated a significant association across both Caucasian (TT vs. TC+CC: OR = 0.779; 95% CI: 0.622, 0.976; P = 0.030) and Asian (T vs. C: OR = 0.895; 95% CI: 0.808, 0.992; P = 0.035) populations. There was also a significant association in Behcet’s disease, rheumatoid arthritis, systemic lupus erythematosus, and ulcerative colitis populations.ConclusionsOur meta-analysis suggested that the miRNA-499 rs3746444 polymorphism was associated with an elevated risk of autoimmune diseases in the overall analysis as well as Caucasian and Asian populations.

SOD2 rs4880 and GPX1 rs1050450 polymorphisms do not confer risk of COVID-19, but influence inflammation or coagulation parameters in Serbian cohort

ABSTRACT Objectives: Due to the role of oxidative stress in the pathophysiology of COVID-19, it is biologically plausible that inter-individual differences in patients’ clinical manifestations might be affected by antioxidant genetic profile. The aim of our study was to assess the distribution of antioxidant genetic polymorphisms Nrf2 rs6721961, SOD2 rs4880, GPX1 rs1050450, GPX3 rs8177412, and GSTP1 (rs1695 and rs1138272) haplotype in COVID-19 patients and controls, with special emphasis on their association with laboratory biochemical parameters. Methods: The antioxidant genetic polymorphisms were assessed by appropriate PCR methods in 229 COVID-19 patients and 229 matched healthy individuals. Results: Among examined polymorphisms, only GSTP1 haplotype was associated with COVID-19 risk (p = 0.009). Polymorphisms of SOD2 and GPX1 influenced COVID-19 patients’ laboratory biochemical profile: SOD2*Val allele was associated with increased levels of fibrinogen (p = 0.040) and ferritin (p = 0.033), whereas GPX1*Leu allele was associated with D-dimmer (p = 0.009). Discussion: Our findings regarding the influence of SOD2 and GPX1 polymorphisms on inflammation and coagulation parameters might be of clinical importance. If confirmed in larger cohorts, these developments could provide a more personalized approach for better recognition of patients prone to thrombosis and those for the need of targeted antiox­idant therapy.

Association of ALDH2 rs671 and MTHFR rs1801133 polymorphisms with hypertension among Hakka people in Southern China

BackgroundGenetic factors play an important role in susceptibility to hypertension. Herein, the association between acetaldehyde dehydrogenase 2 (ALDH2) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hypertension was analyzed among Hakka population in southern China.MethodsA total of 3057 hypertensive patients and 2215 controls were enrolled. The ALDH2 rs671 and MTHFR rs1801133 genotyping were analyzed using gene chip. Relevant information and medical records of these subjects were collected.ResultsHypertensive patients with ALDH2 rs671 G/A heterozygous had lower systolic blood pressure (SBP) than other genotypes (P < 0.001), while hypertensive patients with A allele had lower diastolic blood pressure (DBP) than patients with G allele (P < 0.001). The level of plasma homocysteine (Hcy) in patients with MTHFR CC, CT and TT genotypes showed an increasing trend (P < 0.001). The ALDH2 G/A genotype in the co-dominant model (adjusted OR 1.251, 95% CI 1.024–1.528, P = 0.028) and ALDH2 A/A genotype in the recessive model (adjusted OR 1.221, 95% CI 1.008–1.478, P = 0.041) were significant risk factors for the presence of hypertension. The MTHFR C/T genotype in the co-dominant model (adjusted OR 1.307, 95% CI 1.039–1.643, P = 0.022) and MTHFR C/T and T/T genotypes in the dominant model (adjusted OR 1.281, 95% CI 1.146–1.430, P < 0.001) were significant risk factors for the presence of hypertension. Further, logistic regression analysis showed that age, smoking, alcohol consumption, hyperhomocysteinemia, and high level of serum TG, Apo-A1, Apo-B were significant risks for hypertension.ConclusionsIn summary, ALDH2 rs671 G/A, A/A genotypes and MTHFR rs1801133 C/T, T/T genotypes may be risk factors for hypertension in this Chinese Hakka population.

Association of MTHFR Polymorphisms with H-Type Hypertension: A Systemic Review and Network Meta-Analysis of Diagnostic Test Accuracy

Purpose An association between MTHFR polymorphisms and H-type hypertension (H-HTN) has been investigated by epidemiological studies, but results have been inconsistent. Thus, a systematic assessment of the association was performed based on a literature review and pooled analysis, to provide stronger evidence on the effects of single nucleotide polymorphisms on H-HTN risk. Methods Three investigators independently retrieved relevant studies in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database, and China Biomedical Literature Database (CBM). A fixed or random effects model was selected to calculate pooled odds ratio (OR) and 95% confidence intervals (CIs). A network meta-analysis of diagnostic test and Thakkinstian's algorithm were used to select the most appropriate genetic model, along with false-positive report probability (FPRP) for noteworthy associations. All data were processed using Stata 15.0 and Meta-Disc. Results A total of 14 studies involving 1759 cases and 1581 controls for MTHFR were included in our meta-analysis. In a direct meta-analysis, we found that MTHFR C667T rs1801133 significantly increased the risk of H-HTN susceptibility except for an overdominant model. However, MTHFR A1298C rs1801131 polymorphism had no significant correlation with H-HTN risk. Besides, MTHFR C667T rs1801133 is a potential diagnostic biomarker for estimating H-HTN risk. The results indicated that the dominant model was an optimal diagnosis model for excluding diseases, which could reduce a missed diagnosis rate and further improve the accuracy of disease diagnosis. Conclusion The present result suggests that MTHFR C667T rs1801133 polymorphism is associated with H-HTN risk and may act as a promising predictive biomarker for H-HTN risk. However, further well-designed studies are warranted to confirm these results.

Association of genetic polymorphisms in DNA repair genes ERCC2 Asp312Asn (rs1799793), ERCC2 Lys 751 Gln (rs13181), XRCC1 Arg399 Gln (rs25487) and XRCC3 Thr 241Met (rs861539) with the susceptibility of lung cancer in Saudi population

This study demonstrated the association of polymorphisms in ERCC2 (Asp312Asn) rs1799793, ERCC2 (Lys751Gln) rs13181, XRCC1 (Arg399Gln) rs25487 and XRCC3(Thr241Met) rs861539 polymorphisms with a susceptibility of lung cancer (LC) onset in the Saudi population. The study was performed on 134 LC patients and 270 controls. The data revealed that there was no significant association of LC with subtype squamous cell carcinoma (SCC), small cell lung cancer (SCLC) and adenocarcinoma with the ERCC2 rs1799793 polymorphism. The data showed that the CC genotype for ERCC2 rs13181, the AA genotype for XRCC1 rs25487, and the genotype TT for XRCC3 rs861539 were significantly associated with SCC susceptibility (p < 0.05). Similarly, the CC genotype for ERCC2 rs13181 and the AA genotype for XRCC1 rs25487 were significantly associated with adenocarcinoma susceptibility (p < 0.05). Whereas, the TT genotype for XRCC3 rs861539 was significantly associated with SCLC susceptibility (p = 0.005). In total, significant association of LC susceptibility was found in the following combination models of recessive genotypes: AC heterozygous for ERCC2 rs13181 + AA homozygous for XRCC1 rs25487, CC homozygous for ERCC2 rs13181 + GA heterozygous for rs25487, CC homozygous for rs13181 + AA homozygous for XRCC1 rs25487, CC homozygous for ERCC2 rs13181 + TT homozygous for XRCC3 rs861539, GA heterozygous for XRCC1 rs25487 + CT heterozygous for XRCC3 rs861539, GA heterozygous for XRCC1 rs25487 + TT homozygous for XRCC3 rs861539, AA homozygous for XRCC1 rs25487 + CT heterozygous for XRCC3 rs861539, AA homozygous for XRCC1 rs25487+ TT homozygous for XRCC3 rs861539. These data clearly demonstrated that the combination of recessive genotypes may be associated with susceptibility of LC onset (p < 0.05). In short, the data indicated that DNA repair genes increase LC risk via gene-gene interaction rather than independent variants.

Association of miR-146a rs2910164 G/C polymorphism with its abnormal expression and risk of gastric cancer

To assess the influence of rs2910164 G/C single nucleotide polymorphism (SNP) of the miR-146a gene on its expression and susceptibility to gastric cancer. Fifty three gastric cancer patients and six gastric cancer cell lines were selected for determining the miR-146a expression by Taqman quantitative PCR. A model was constructed to assess the influence of miR-146a overexpression on the growth of AGS gastric cancer cells. A case-control study involving 417 gastric cancer patients and 420 cancer-free individuals was then conducted, and the allelic and genotypic frequencies of the rs2910164 G/C SNP were compared. The genotypes of all subjects were determined by using a Taqman allelic discrimination assay. A Taqman assay was also used to quantify mature and pri-miR-146a transcripts among 65 gastric cancer patients with known genotypes. The expression of miR-146a was down-regulated among the 53 gastric cancer patients and six gastric cancer cell lines. Over-expression of miR-146a has suppressed the growth of gastric cancer by inhibiting the G1/S-phase transition of AGS cells. The case-control study showed that subjects with GC/CC genotypes had significantly lower risk for gastric cancer compared with those with GG genotype. In addition, miR-146a G/C SNP has significantly increased the level of mature miR-146a in those with GC/CC genotype compared with GG genotype. Down-regulation of miR-146a may play an important role in the pathogenesis of gastric cancer. The rs2910164 polymorphism of the miR-146a gene may reduce the risk of gastric cancer by influencing the processing of mature miR-146a.

Understanding Role of DNA Repair and Cytochrome p-450 Gene Polymorphisms in Cervical Cancer Patient Treated With Concomitant Chemoradiation.

Background: Evidences suggest that single nucleotide polymorphisms (SNPs) can be considered as potential biomarkers for disease progression and therapeutic response in cervical cancer. The present study investigated the association of CYP1A1 T>C (rs4646903), CYP1A1 A>G (rs1048943), CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), XRCC1 G>A (rs25487), XRCC2 G>A (rs3218536) and XRCC3 C>T (rs861539) polymorphisms with treatment outcome of cisplatin based chemoradiation (CRT). Methods: Total 227 cervical cancer cases, treated with the same chemoradiotherapy regimen were selected for the study. Genotyping analysis was performed by PCR-restriction fragment length polymorphisms (PCR-RFLP). Treatment response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Association of all clinical data (responses, recurrence and survival of patients) and single nucleotide polymorphisms (SNPs) was analysed by using SPSS (version 21.0). Results: Patients with TA/AA genotype of CYP2E1 T>A polymorphism showed significantly poor response while those with GC/CC genotype of RAD51 G>C showed better response (p = 0.008, p = 0.014 respectively). Death was significantly higher in patients with GG genotypes of RAD51 G>C and XRCC1 G>A (p = 0.006, p = 0.002 respectively). Women with GC+CC genotype of RAD51 G>C and AG+GG of XRCC1 showed better survival and also reduced risk of death (HR = 0.489, p = 0.008; HR = 0.484, p = 0.003 respectively). Conclusion: Results suggested that CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), and XRCC1 G>A (rs25487) polymorphisms may be used as predictive markers for clinical outcomes in cervical cancer patients undergoing cisplatin based concomitant chemoradiotherapy.

Methylenetetrahydrofolate Reductase Gene rs1801133 and rs1801131 Polymorphisms and Essential Hypertension Risk: A Comprehensive Analysis.

Background Essential hypertension (EH) is a common and multifactorial disorder that is likely to be influenced by multiple genes. The methylenetetrahydrofolate reductase (MTHFR) gene rs1801133 and rs1801131 polymorphisms influence MTHFR enzyme activity and plasma homocysteine concentration. In addition, variations in MTHFR functions likely play roles in the etiology of EH. Thus far, a large number of studies investigating the associations between the MTHFR polymorphisms and EH have provided controversial or inconclusive results. To better assess the purported relationship, we performed a comprehensive analysis of 52 published studies. Objective and Methods. Eligible studies were identified by searching the PubMed, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the potential association between the MTHFR rs1801133 polymorphism and EH. Results Overall, 10712 patients and 11916 controls were involved; we observed significantly increased association between the MTHFR rs1801133 polymorphism and EH risk (such as T vs. C: OR = 1.38, 95% CI = 1.25 − 1.54, P ≤ 0.001), with similar results evident within race subgroups (such as Asian: T vs. C: OR = 1.47, 95% CI = 1.30 − 1.67, P ≤ 0.001; compared to Chinese: T vs. C: OR = 1.54, 95% CI = 1.33 − 1.79, P ≤ 0.001). Similar associations were also found in subgroups defined by the source of controls and genotype methods. To our regret, based on the limited studies, no association was detected for rs1801131 polymorphism. Conclusions Our study provides evidence that the MTHFR rs1801133 null genotype may increase EH risk. Future studies with larger sample sizes are warranted to evaluate this association in more detail.

Structure of the distribution of genetic determinants of the efficacy and safety of non-steroidal anti-inflammatory drugs in the Russian population: focus on CYP2C8, PTGS1 and PTGS2

The efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) may be determined by the polymorphic nature of the CYP2C8, PTGS1 and PTGS2 genes.Objective: to analyze the nature of the distribution of CYP2C8*3 (rs10509681), CYP2C8*3 (rs11572080), PTGS1 (rs10306135), PTGS1 (rs12353214) and PTGS2 (rs20417) among residents of the North Caucasus.Patients and methods. The study involved 676 volunteers from Russian, Balkar, Kabardian and Ossetian ethnic groups. Carriage of polymorphic markers CYP2C8, PTGS1 and PTGS2 was determined using real-time polymerase chain reaction.Results and discussion. There were no significant differences between the groups in the rs10509681 and rs11572080 variants of the CYP2C8 gene. In all groups, the carriage of a combination of CYP2C8 and CYP2C9 alleles, encoding the phenotype of normal metabolizers, prevailed with a frequency of about 75% or more. The rs10306135 variant of the PTGS1 gene was found in 5.9% of Russians, 1.1% of Balkars, 5.3% of Kabardians, and 10.6% of Ossetians; variant rs12353214 – in 19.1; 9.4; 10.8 and 9.2%, rs20417 polymorphism of the PTGS2 gene in 0.4; 5; 2.8 and 3.1% respectively.Conclusion. The data obtained can be used to develop a more rational approach to the prescription of NSAIDs, taking into account the genetic characteristics of the local population in ethnic regions.

Association of the DNA Methyltransferase and Folate Cycle Enzymes' Gene Polymorphisms with Coronary Restenosis.

Background: In recent years, the interest in genetic predisposition studies for coronary artery disease and restenosis has increased. Studies show that polymorphisms of genes encoding folate cycle and homocysteine metabolism enzymes significantly contribute to atherogenesis and endothelial dysfunction. The purpose of this study was to examine some SNPs of genes coding for folate cycle enzymes and DNA methyltransferases as risk factors for in-stent restenosis. Methods: The study included 113 patients after stent implantation and 62 patients without signs of coronary artery disease at coronary angiography as the control group. Real-time PCR and RFLP-PCR were applied to genotype all participants for MTHFR rs1801133, MTHFR rs1801131, MTR rs1805087, MTRR rs1801394, DNMT1 rs8101626, DNMT3B rs1569686, and DNMT3B rs2424913 gene polymorphisms. Statistical data processing was carried out using the R language and the SPSS Statistics 20 software. Results: Statistically significant differences in the DNMT3B gene polymorphisms were found between patients with and without in-stent restenosis. An association of TT rs1569686 and TT rs2424913 genotypes with the development of restenosis was revealed. The TT rs1569686 genotype was more frequent in the patients under the age of 65 years and in the subgroup of patients with post-12-month restenosis, as was the minor GG genotype for MTR rs1805087. The homozygous TT genotype for MTHFR rs1801133 was significantly more frequent in the subgroup over 65 years old. The frequencies of the heterozygous genotype for the MTRR gene and the minor GG homozygotes for the DNMT1 gene were significantly higher in the subgroup with in-stent restenosis under 65 years old. Conclusions: The results of this study could be used for a comprehensive risk assessment of ISR development, determining the optimal tactics and an individual approach in the treatment of patients with coronary artery disease before or after percutaneous coronary interventions, including homocysteine-lowering treatment in patients with hyperhomocysteinemia and a high risk of in-stent restenosis.