Rs2910164 Polymorphism Research Articles

Aldehyde Dehydrogenase 2 rs671 G/A and a/A Genotypes are Associated with the Risk of Acute Myocardial Infarction.

Aldehyde dehydrogenase 2 (ALDH2) is a key catalytic enzyme involved in the aldehyde metabolism that plays an important role in the occurrence and development of acute myocardial infarction (AMI). However, the relationship of ALDH2 polymorphism and susceptibility to AMI may differ among different regions and populations, and it has not yet been reported in Hakka population. The purpose of the present study was to investigate it in this population. Four hundred and nineteen AMI patients and 636 individuals without AMI were included in the present study. The ALDH2 rs671 polymorphism was genotyped using polymerase chain reaction (PCR)-microarray. Differences in ALDH2 rs671 genotypes and alleles between patients and controls were compared, and the relationship between ALDH2 rs671 genotypes and AMI risk was analyzed. Patients with AMI had a lower frequency of ALDH2 rs671 G/G genotype (43.2% vs 52.7%, p=0.003), and a higher G/A genotype (45.6% vs 38.5%, p=0.025) than controls. And AMI patients had a lower frequency of ALDH2 rs671 G allele (66.0% vs 71.9%), and a higher A allele (34.0% vs 28.1%) (p=0.004) than controls. Logistic regression analysis showed that overweight (body mass index (BMI)≥24.0 kg/m2 vs BMI 18.5-23.9 kg/m2: odds ratio (OR) 2.046, 95% confidence interval (CI): 1.520-2.754, p<0.001), history of hypertension (yes vs no: OR 3.464, 95% CI: 2.515-4.770, p<0.001), ALDH2 rs671 G/A genotype (G/A vs G/G: OR 1.476, 95% CI: 1.102-1.976, p=0.009), and A/A genotype (A/A vs G/G: OR 1.656, 95% CI: 1.027-2.668, p=0.038) maybe the independent risk factors for AMI. Overweight (BMI≥24.0 kg/m2), a history of hypertension, and ALDH2 rs671 G/A or A/A genotypes increased the risk of developing AMI in Hakka population.

Association of Methylenetetrahydrofolate Reductase rs1801133 Polymorphism with osteoporosis and fracture risk in Taiwan.

Introduction: Osteoporosis is a prevalent skeletal disorder influenced by age, hormonal changes, medication use, nutrition, and genetics. The relationship between MTHFR and osteoporosis remains unclear, especially in Asians. The aim of our study was to elucidate the impact of MTHFR on osteoporosis and fracture risk. Materials and Methods: Participants were recruited from the Taiwan Precision Medicine Initiative at Taichung Veterans General Hospital. A total of 3,503 subjects with available bone mineral density measurements were selected. Using the Axiom Genome-Wide TWB 2.0 Array, we identified the MTHFR rs1801133 variant. Among these subjects, 1,624 patients carrying the variant were included in the case group, while the remaining 1,879 patients without the variant served as the control group. Results: Overall, individuals carrying the MTHFR rs1801133 variant exhibited a significantly elevated risk of developing osteoporosis. Stratified analysis by different genotypes, the results revealed a statistically significant association between the heterozygous genotype of MTHFR rs1801133 and osteoporosis. However, there was no significant correlation between MTHFR genotypes and fracture risk. Furthermore, subgroup analysis of female patients revealed age, a known risk factor, was associated with both osteoporosis and fractures. Interestingly, the presence of the MTHFR rs1801133 variant did not confer an increased risk of osteoporosis or fractures in females. Conclusion: Our study revealed a notable increase in the prevalence of osteoporosis among individuals carrying the MTHFR rs1801133 variant. Nevertheless, these individuals did not exhibit a heightened risk of major or hip fractures compared to non-carriers. Our findings could be of value in raising awareness of the increased risk of osteoporosis among individuals with this genetic variant.

The Relationship Between the hOGG1 rs1052133 Polymorphism and the Occurrence of Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

Objectives: Exploring the relationship between the hOGG1 rs1052133 polymorphism and the occurrence of nasopharyngeal carcinoma (NPC). Methods: PubMed, Web of Science, Scopus, CNKI, Wanfangdata, and VIP were used to search for studies and the NOS evaluation scale was used to evaluate the quality. All studies were grouped according to different genotypes. The Cochrane's Q test and I2 test were used for heterogeneity evaluations. If heterogeneity was small, the fixed effects model was used, and conversely, the random effects model was used. Publication bias was also detected. P < .05 in all results indicated statistically significant. Results: We ultimately included 6 studies with 2021 NPC patients in the study group and 2375 healthy populations in the control group. After meta-analysis, it was found that the total OR value of the "Ser/Cys (CG) vs Ser/Ser (CC)" group was 1.00 (95% CI: 0.85-1.18) and the "Cys/Cys (GG) vs Ser/Ser (CC)" group was 1.06 (95% CI: 0.87-1.28). These results were not statistically significant (P > .05). Furthermore, the integrated total OR values of each group were not statistically significant with or without the smoking history, even in other genotype models (Allele, Dominant, Recessive, and Additive) (P > .05). Conclusion: There is no clear correlation between the hOGG1 rs1052133 polymorphism and the occurrence of NPC, even with or without the smoking history.

Can TERT rs2853669 polymorphysm indicate fibrosis in sarcoidosis?

Sarcoidosis is a systemic inflammatory disease of unknown cause, characterized by the presence of non-caseating granulomas, which can affect all organs in the body, especially the lung. The fibrotic stage 4 of sarcoidosis usually does not respond adequately to treatment and may cause respiratory distress in the patient. Some telomerase gene polymorphisms have been significantly associated with lung cancer and idiopathic pulmonary fibrosis. In our study, we aimed to investigate the relationship between telomerase mutation and progression to fibrosis in patients with sarcoidosis. A total of 93 patients, including 18 males and 73 females, who were clinically and histopathologically diagnosed with sarcoidosis were included in the study. The 78 patients included in the study were classified as non-fibrotic and 15 as fibrotic sarcoidosis. In telomerase rs2853669 single nucleotide polymorphism, three genotypes, homozygous TT, homozygous CC and heterozygous TC, were determined as the genotypes of the patients. When non-fibrotic and fibrotic sarcoidosis groups were compared, no significant difference was found in terms of genotypes (p=0.76). The FEV1 (forced expiratory volume in the first second) % of the CC genotype was lower than that of the other genotypes (p=0.01). In sarcoidosis patients, telomerase rs2853669 polymorphism does not indicate progression to fibrosis, but since FEV1% was found to be lower in individuals with homozygous CC polymorphism, it is thought that it may predict loss of respiratory function. Further studies are needed to evaluate the association of telomerase polymorphisms with fibrosis in sarcoidosis.

ALDH2 deficiency exacerbates MCD-diet induced MASLD by modulating bile acid metabolism

Aldehyde dehydrogenase 2 (ALDH2), an acetaldehyde dehydrogenase in mitochondria, is primarily responsible for metabolizing alcohol-derived acetaldehyde and other endogenous aldehydes. Inactivating ALDH2 rs671 polymorphism is found in up to 8 % of the global population and 40 % of the East Asian population. Recent studies have shown that rs671 SNP mutation in the human ALDH2 gene is associated with an increased risk of metabolic dysfunction-associated steatotic liver diseases (MASLD), but the mechanism remains unclear. Here, we identify the role of ALDH2 in MASLD. Firstly, ALDH2 activity was lower in MASLD patients and the methionine-choline deficiency (MCD) diet induced MASLD model. Secondly, activation of ALDH2 activity with Alda-1 (ALDH2 agonist) attenuated MCD-diet induced hepatic triglyceride (TG) accumulation and steatosis, whereas the opposite result was observed with cyanamide (CYA, ALDH2 inhibitor). Furthermore, ALDH2 deficiency exacerbated hepatic steatosis, inflammation, and fibrosis in the MCD-diet induced mice. RNA sequencing (RNA-seq) revealed that oxysterol 7-α hydroxylase (Cyp7b1) and the related metabolic pathway significantly changed in the MCD-diet challenged ALDH2−/− mice. In ALDH2−/− mice, the expression of Cyp7b1 was downregulated and FXR/SHP signaling was inhibited, reducing the alternative bile acid (BA) synthetic pathway. In our in vitro experiments, knockdown of ALDH2 exacerbated TG accumulation in hepatocytes, whereas the opposite result was observed with overexpression of ALDH2. Moreover, chenodeoxycholic acid (CDCA) rescued ALDH2 downregulation induced TG accumulation in hepatocytes. Our study reveals that ALDH2 attenuates hepatocyte steatosis by regulating the alternative BA synthesis pathway, and ALDH2 may serve as a potential target for the treatment of MASLD.

Association between the XRCC3 rs861539 Polymorphism and Breast Cancer Risk: An Updated Meta-Analysis

Association between the XRCC3 rs861539 Polymorphism and Breast Cancer Risk: An Updated Meta-Analysis

Effect of miR-146a polymorphism on lipoic acid therapy in patients with T2DM peripheral polyneuropthy.

For investigating the impact of miR-146a rs2910164 polymorphism on the therapeutic efficacy of lipoic acid therapy in patients with type 2 diabetes mellitus (T2DM) peripheral neuropathy (DPN). 106 T2DM-DPN patients in our hospital from Jan. 2020- 2022 were selected. The probe detection method was utilized to determine the polymorphism of the miR-146a rs2910164 gene in peripheral blood. All patients were treated with zinc sulfate for 3 weeks period. According to the treatment effect, 37 patients who were ineffective in treatment will be divided into an ineffective group, and 79 patients who were effective in treatment will be divided into an effective group. The condition of miR-146a gene peptides was analyzed after treatment in both groups. The motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), and Toronto Clinical Scoring System (TCSS) scores of the median nerve and common peroneal nerve with different genotypes were compared between the 2 sets. The genotype frequencies of alleles G, GG, and GC in the valid group were lower than those in the invalid group; After treatment, MNCV and SNCV of CC genotype median nerve and common peroneal nerve in DPN patients were higher than those before treatment; The TCSS scores of the three genotypes less than post-treatment. The above results showed statistically significant differences (P<0.05). Lipoic acid is influenced by the miR-146a polymorphism gene in the treatment of T2DM-DPN patients, with the CC genotype having a lower susceptibility and the best clinical treatment effect.

Association Analysis of a GSTP1 Functional Polymorphism with Methamphetamine Dependence and Associated Symptoms in a Multiethnic Malaysian Population

Methamphetamine (METH) is a psychostimulant that is highly addictive and has been widely linked to the adverse effect on brain. METH-induced oxidative stress can be effectively protected by glutathione S-transferases (GSTs). Genetic polymorphism of GST gene family may affect the susceptibility of METH users to its dependence and associated symptoms. Therefore, this study investigated the association of a functional single nucleotide polymorphism rs1695 of GSTP1 gene with METH-induced symptoms and dependence in a Malaysian population, including Malay, Chinese, Kadazan-Dusun, and Bajau ethnic groups. Genotyping for GSTP1 rs1695 polymorphism from 230 METH-dependent male subjects and 232 healthy male controls was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP). For statistical analyses, the χ2 test and Fisher’s were performed in this research. The results showed a significant difference between GSTP1 rs1695 polymorphism and METH dependence in the Malay and Chinese populations. Our findings suggest that the GSTP1 rs1695 polymorphism may have possibility to methamphetamine dependence in the Malay and Chinese populations but not in other ethnicities. Furthermore, the Malay ethnic group who carried the -105G allele might have a protective role for METH-induced mania.

CDKN2B-AS (rs2891168), SOD2 (rs4880), and PON1 (rs662) polymorphisms and susceptibility to coronary artery disease and type 2 diabetes mellitus in Iranian patients: A case-control study.

Coronary artery disease (CAD) is a devastating illness and primary cause of death worldwide that arises from a combination of genetic and environmental factors. Several large-scale studies found that 9p21.3, superoxide dismutase 2 (SOD2), and paraoxonase 1 (PON1) polymorphisms increase type 2 diabetes mellitus (T2DM) and/or coronary artery disease (CAD) risk. Our research aimed to investigate whether the SNPs of the 9p21.3 locus (rs28911698), SOD2 (rs4880), and PON1 (rs662) genes were associated with the risk of T2DM and/or CAD in the Iranian population. In this case-control study four group subjects including patients with CAD non-T2DM, with CAD and T2DM, non-CAD with T2DM, and non-CAD non-T2DM were recruited to the study from 2019 to 2020. Molecular analysis was carried out by allele specific-polymerase chain reaction (AS-PCR) technique for rs4880, Taqman genotyping assay for rs2891168, and PCR followed by restriction fragment length polymorphism (PCR-RFLP) technique for rs662. The rs2891168 polymorphism presented an elevated risk of CAD in non-T2DM with CAD and with T2DM CAD groups compared to the non-T2DM non-CAD group with GG genotype and dominant model after adjustment (p < 0.05). G-allele in PON1 rs662 polymorphism associated with increased risk of T2DM in T2DM non-CAD, and T2DM CAD groups compared to non-T2DM non-CAD group with dominant model, GG and AG genotypes (p < 0.05). However, SOD2 rs4880 polymorphism presented no significant association with the development of diabetes or CAD. These results provide a prime witness that rs2891168 and rs662 gene variants might have a possible increased risk of CAD and T2DM occurrence, respectively. To obtain more definitive and accurate results in this area, further research is required.

Polymorphisms of TP53 gene and its association with colorectal cancer: A case-control investigation

The tumor suppressor gene (TP53) is crucial for DNA repair mechanism, apoptosis, and cell cycle regulation and progression. In human cancer, TP53 is mutated and highly polymorphic. In the current case-control research investigation, we investigated TP53 gene SNPs, in exonic and intronic regions, as potential risk factors for colorectal cancer (CRC). This study comprised of 192 patients and 192 control. Obtained data illustrated that only the G allele; rs1042522 (Pro72Arg (C > G), demonstrated a statistically significant association, almost 1.5-fold induction promotes the risk of CRC development in contrast to individuals with the C allele (OR = 1.5, χ2 = 7.28, p = 0.00696). The homozygous variant GG genotype of rs1042522 was also a significant risk factor to CRC development (OR = 2.1, χ2 = 6.41, p = 0.01136). SNP rs1042522 polymorphism established a considerably elevated odds of CRC among male patients aged < 57 years and in patients’ with tumors situated in colon region. In silico analysis exhibited that proline to arginine amino acid substitution affects the protein structure. Both rs1642785 and rs9894946 SNPs did not demonstrate any significant statistical association with CRC. In conclusion, this study confirmed that rs1042522 SNP within TP53 gene is correlated with possibility of developing CRC in the Saudi population. This finding highlights those polymorphisms within TP53 gene could act as a diagnostic indicator for CRC.

Assessment of the relationship between miR-499C/T (rs3746444) polymorphism and lung carcinoma in Iranian population; a case-control study.

Lung carcinoma is characterized by uncontrollable division of respiratory system cells with detrimental and lethal consequences on human health. Critical roles of microRNAs (miR) are scientifically approved in biological and pathological pathways, such as the role of miR-499 (rs3746444) in lung carcinomas. Thus, in this case-control investigation, we aimed to assess the probable relationship between miR-499C/T variant and the occurrence of lung carcinoma in Iranian population for the first time. Genotype of miR-499 polymorphism was described by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay in patients and healthy individuals. Following definite diagnosis of lung carcinoma, the blood samples were collected, and the DNA extraction was performed by Salting-Out method. Finally, data were analysed by SPSS (v. 20) and the significant level was considered p-value<0.05. Statistically, the frequency of combined genotypes of CC+CT were 83.33% and 35% and TT+CT were 100% and 92% in case and control individuals, respectively. Also, individuals with genotypes of TC (OR: 3.08, CI95%: 3.03-3.17, p<0.0001), TC+CC (OR: 0.10, CI95%: 0.05-0.23, p<0.0001), CC (OR: 0, CI95%: 0.00-0.60, p=0.0214), and TC (OR: 0.07, CI95%: 0.030.15, p<0.0001) represented statistically significant (p<0.05) differences lung carcinoma than those with TT, TT, TT+TC, and TT+CC genotypes, respectively. The frequency of miR-499C (78.5%) and miR-499T (21.5%) alleles were also statistically significantly (p<0.05) difference associated with lung carcinoma in patients than controls. In this study, a possible relationship among miR-499C/T polymorphism and lung carcinoma was detected in Iranian population. Since this study was conducted for the first time, thus other supplementary assessments are needed for definite conclusion.

Polymorphisms in ERCC1, ERCC4 and ERCC5 genes as biomarkers of susceptibility for pesticide-induced DNA damage in North-West Indian agricultural workers

BackgroundOccupational pesticides exposure has raised health concerns due to genotoxicity and accumulation of DNA damage. Polymorphisms in genes encoding enzymes involved in nucleotide excision repair (NER) may affect the individual’s susceptibility to pesticide toxicity.MethodsThis study evaluates the association of excision repair cross complementation group 1 (ERCC1) (8092 C > A, 3’UTR, rs3212986) and ERCC1 (19007 C > T, Asn118Asn, rs11615), ERCC4 (1244 G > A, Arg415Gln, rs1800067) and ERCC5 (3507 G > C, Asp1104His, rs17655) polymorphisms with pesticide-induced DNA damage in North-West Indian agricultural workers. The study population comprised 225 agricultural workers exposed to pesticides and 225 non-exposed controls.ResultsOur study demonstrate that exposed workers carrying variant ERCC1 8092AA genotype showed higher total comet DNA migration (p = 0.015) as well as increased frequency of cells showing DNA migration (p = 0.027). Exposed agricultural workers with variant ERCC4 1244AA (415Gln/Gln) and ERCC5 3507CC (1104His/His) genotypes exhibited elevation in total comet DNA migration (p < 0.01). However, genotypes of ERCC1 19007 C > T (Asn118Asn) showed no association with total comet DNA migration (p = 0.963), frequency of cells showing DNA migration (p = 0.423) as well as mean tail length (p = 0.432).ConclusionERCC1, ERCC4 and ERCC5 polymorphisms influence DNA damage and can be used as biomarkers of susceptibility for pesticide-induced DNA damage in North-West Indian agricultural workers.

Impact of XRCC3 rs861539 and XPD rs13181 gene polymorphisms on childhood acute lymphoblastic leukemia in Egyptian patients

Abstract Background There is mounting evidence that the genotypes of DNA repair proteins and susceptibility to certain malignancies are related. Few studies, however, have examined the role of the homologous repair gene X-ray repair cross-complementing group 3 (XRCC3) genotype and xeroderma pigmentosum complementation group D (XPD) in the development or prognosis of acute lymphoblastic leukaemia (ALL). Aim of the study In this study, we investigated the impact of XRCC3 rs861539 and XPD rs13181 polymorphisms on the risk of ALL. To the best of our knowledge, this is the first report of XRCC3 and XPD polymorphisms in ALL Egyptian patients. Methods Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used to analyse XRCC3 rs861539 and XPD rs13181 gene polymorphisms in 96 patients with ALL and in 103 disease-free controls, who were of a similar age. Results ALL risk is lower in individuals with the homozygous variant TT genotype at XRCC3 rs861539. The heterozygous variant CT genotype of XRCC3 was connected to increased disease risk of ALL in males. Additionally, C allele frequency was noticeably higher than T allele frequency in pre B ALL. In this investigation, there was no correlation between the XPD Lys751 rs13181 polymorphism and risk of ALL. Conclusion Our research reveals that genetic variation in the genes for DNA repair may influence ALL susceptibility.

Association of HOTAIR gene rs920778 (C > T) and rs4759314 (A > G) polymorphism with breast cancer in Egyptian women

BackgroundHox transcript antisense RNA (HOTAIR) is considered an oncogene associated with the initiation and progression of many malignancies. Previous studies have examined the connection between HOTAIR SNPs rs4759314 and rs920778 for breast cancer (BC), getting variable results in multiple ethnicities. Therefore, this study was designed to evaluate the connection between these two SNPs and disease vulnerability, clinic-laboratory, and hormonal parameters, featuring status associations with the BC risk in an Egyptian woman sample.Methods and resultsIn this case-control study, DNA was taken from the blood of 100 BC patients and 100 unrelated healthy Egyptian females. The characterization of rs4759314 was genotyped using the T-ARMS-PCR method and rs920778 using the SNP-RFLP technique for all participants. The frequency of the rs4759314 A > G variation revealed a statistically significant increase in BC risk with dominant (p = 0.013, OR = 1.592, 95% Cl = 1.105–2.293), co-dominant (p = 0.006, OR = 2.314, 95%Cl = 1.278–4.191) and overdominant (p = 0.002, OR = 2.571, 95% Cl = 1.430–4.624) genetic models. On the other hand, the rs920778 C > T polymorphism was not significantly associated with BC. ER/PR positivity with HER2 negativity was significantly associated with the AA genotype compared to the AG genotype. Otherwise, no significant associations between the two SNPs and clinical stage or hormonal features could be found. In conclusion, the rs4759314 A > G SNP in the HOTAIR gene is strongly associated with BC, which might warrant its determination among affected families for prevention and early treatment.

THE CONTENT OF ENDOTHELIN-1 IN THE BLOOD PLASMA OF PATIENTS WITH DIABETIC RETINOPATHY ON THE BACKGROUND OF TYPE 2 DIABETES DEPENDING ON THE POLYMORPHIC VARIANTS OF THE MTHFR, MTRR AND MTR GENES

Backround. The vascular and extravascular microcirculation of the eye is a rich source of endothelin-1 (ET-1), which can contribute to abnormal retinal hemodynamics in diabetic retinopathy. In patients with type 2 diabetes mellitus (T2DM), an increase in the level of circulating ET-1 was found, and a positive correlation between its levels in the blood was found and degree of microangiopathy. Strengthens the development of endothelial dysfunction and microvascular complications, a high level of homocysteine, which occurs due to a genetically determined deficiency of enzymes of the folate cycle, determines in the body what, because homocysteine ​​causes a violation of the structure of endothelial cells.&#x0D; Aim: to study the ET-1 content in the blood plasma of patients with diabetic retinopathy against the background of type 2 diabetes, depending on the polymorphic variants of the MTHFR, MTRR and MTR genes, as an important pathogenetic pathway for the development of endothelial dysfunction.&#x0D; Materials and methods. The study included 83 patients (83 eyes) with T2DM, in whom non-proliferative and proliferative DR were found according to the results of an ophthalmological examination using the ETDRS scale. The control group (CG) included 35 people without diabetes, who were matched with patients by gender, age, and body mass index. Gene polymorphism was determined using real-time PCR on the automatic amplifier Gene Amp® PCR System 7500, the content of ET-1 was determined in blood plasma by the ELISA method.&#x0D; Conclusion. The SS genotype of the rs1801133 gene, the GG genotype of the rs1805087 gene, the AS polymorphism, and the SS genotype of the rs1801131 gene can be considered potential risk factors for the development of DR on the background of type 2 diabetes.&#x0D; The SS genotype of the rs1801133 gene was accompanied by a maximum 14-fold increase in ET-1 in patients with DR. The minor GG genotype of the rs1805087 gene was found only in patients with DR, and was characterized by the maximum content of ET-1. In the carriers of AS polymorphism of the rs1801131 gene, an 8-fold increase in ET-1 was found during the development of DR.&#x0D; The minor GG genotype of the rs1805087 gene was found only in patients with DR, and was characterized by the maximum content of ET-1. In the carriers of AS polymorphism of the rs1801131 gene, an 8-fold increase in ET-1 was found during the development of DR. The minor SS genotype of this gene was twice as common in patients, and the ET-1 content increased 5 times with the development of DR.&#x0D; The presence of ST polymorphism of the rs1801133 gene and the AA genotype of rs1801131 are probably factors that prevent the development of DR. The ST gene rs1801133 polymorphism was accompanied by the lowest ET-1 content. The AA genotype of the rs1801131 gene was 1.3 times less frequent, the ET-1 content in these individuals was the lowest and practically did not change during the development of DR.

Associations between non-coding RNAs genetic polymorphisms with ovarian cancer risk: A systematic review and meta-analysis update with trial sequential analysis.

This systemic review and meta-analysis seeks to systematically analyze and summarize the association between non-coding RNA polymorphisms and ovarian cancer risk. We searched PubMed, Web of Science and CNKI for available articles on non-coding RNA polymorphisms in patients with ovarian cancer from inception to March 1, 2023. The quality of each study included in the meta-analysis was rated according to the Newcastle-Ottawa Scale.Odds ratios (ORs) with their 95% confidence intervals (95% CI) were used to assess associations. Chi-square Q-test combined with inconsistency index (I2) was used to test for heterogeneity among studies. Lastly, trial sequential analysis (TSA) software was used to verify the reliability of meta-analysis results, and in-silico miRNA expression were also performed. The meta-analysis was registered with PROSPERO (No. CRD42023422091). A total of 17 case-control studies with 18 SNPs were selected, including 2 studies with H19 rs2107425 and HOTAIR rs4759314, and 5 studies with miR-146a rs2910164 and miR-196a rs11614913. Significant associations were found between H19 rs2107425, miR-146a rs2910164, and miR-196a rs11614913 and ovarian cancer risk. Three genetic models of H19 rs2107425 (CT vs TT (heterozygote model): OR = 1.36, 95% CI = 1.22-1.52, P < .00001; CC + CT vs TT (dominant model): OR = 1.12, 95% CI = 1.02-1.24, P = .02; and CC vs CT + TT (recessive model): OR = 1.23, 95% CI = 1.16-1.31, P < .00001), 2 genetic models of miR-146a rs2910164 (allele model: OR = 1.75, 95% CI = 1.05-2.91, P = .03; and heterozygote model: OR = 0.33, 95% CI = 0.11-0.98, P = .05), 3 genetic models of miR-196a rs11614913 (allele model: OR = 0.70, 95% CI = 0.59-0.82, P < .0001; dominant model: OR = 1.62, 95% CI = 1.18-2.24, P = .0001; and recessive model: OR = 0.70, 95% CI = 0.57-0.87, P = .03) were statistically linked to ovarian cancer risk. Subgroup analysis for miR-146a rs2910164 was performed according to ethnicity. No association was found in any genetic model. The outcomes of TSA also validated the findings of this meta-analysis. This study summarizes that H19 rs2107425, miR-146a rs2910164, and miR-196a rs11614913 polymorphisms are significantly linked with the risk of ovarian cancer, and moreover, large-scale and well-designed studies are needed to validate our result.

Associations of leptin receptors and miRNA polymorphisms with susceptibility to hypertension.

Leptin receptors (LEPR) are located in the central nervous system and other tissues including adipocytes and endothelial cells, where they play a key role in mediating the effects of leptin. MicroRNA (miR/miRNA)-27a and miR-155 have been shown to play an important role in the regulation of LEPR expression and are differentially expressed in various diseases. Therefore, the present study analyzed potential associations of LEPR deletion/insertion (Del/Ins), miR-27aA>G (rs895819) and miR-155T>A (rs767649) polymorphisms with a predisposition to hypertension (HTN). Genotyping was performed by a PCR-restriction fragment length polymorphism assay. Frequencies of LEPR Del/Ins and miRNA gene polymorphisms in patients diagnosed with HTN (n=232) and randomly selected healthy controls (n=247) were assessed. The present study found that Del/Ins and Ins/Ins genotypes and the Ins allele of the LEPR Del/Ins polymorphism were associated with a decreased risk of HTN compared with controls, whereas the miR-27aA>G rs895819 polymorphism was associated with an increased risk of HTN. Combined genotype and allele analyses for LEPR Del/Ins and two miRNA polymorphisms revealed an association with an increased risk or a decreased risk of HTN. Furthermore, stratification analysis revealed that HTN risk factors were associated with waist circumference (WC) and high-density lipoprotein cholesterol (HDL-C) values in LEPR Del/Ins polymorphism. They were also associated with body mass index, WC, triglyceride and HDL-C values in miR-27aA>G polymorphism. The present study revealed a combined effect of LEPR Del/Ins and miR-27aA>G polymorphisms on the risk of HTN in Koreans, suggesting that these gene polymorphisms could be potential markers for predicting HTN risk.

A pilot study to examine the association between COX-2 rs5275 polymorphism and the response to repetitive transcranial stimulation in schizophrenia

High frequency (HF)-rTMS has been shown to improve cognitive functions in patients with schizophrenia (SCZ). This study aimed to investigate whether COX-2 rs5275 variants were associated with cognitive improvements following rTMS treatment in patients with SCZ. Forty-eight hospitalized patients with SCZ were assigned to the neuronavigation HF-rTMS group and 28 patients to the sham group over left DLPFC for 1 month. Cognitive function was evaluated using the repeatable battery for the assessment of neuropsychological status (RBANS) at weeks 0 and 4. COX-2 rs5275 polymorphism was genotyped by a technician. At baseline, C allele carriers showed better cognitive performance relative to patients with TT homozygote. Additionally, C allele carriers had greater improvement in memory from the follow-up to baseline following rTMS stimulation, while patients with the TT genotype showed no significant improvement in memory index. More importantly, we found that COX-2 rs5275 was correlated with the response to rTMS after controlling for the covariates. This study data indicate that COX-2 rs5275 was associated with improvements in immediate memory after HF-rTMS treatment in patients with SCZ. rTMS shows an effect on memory only in C allele carriers, but not in those with the TT genotype.

Visual single nucleotide polymorphism (SNP) detection for ALDH2 genotyping based on multiplex ligation probe amplification (MLPA) and lateral flow assay

Current techniques for single nucleotide polymorphism (SNP) detection require laborious experimental procedures, expensive and sophisticated instruments, as well as complex data analysis, which make it difficult to meet the demand for routine clinical laboratories or point of care testing (POCT). In this study, the authors propose a reliable and cost-effective method by integrating multiplex ligation probe amplification (MLPA) and gold nanoparticles (AuNPs)-based lateral flow assay (LFA) for visual detection of the ALDH2 gene rs671(G > A) polymorphism. The genotyping result can be easily observed with the naked eye within 5–10 min after loading the MLPA products on the LFA device. This system demonstrates high sensitivity with LOD down to 1 ng, meeting the requirement in clinical diagnostic. Furthermore, this method has been implemented in clinical practices to identify the genotypes of the ALDH2 gene. The results obtained from the MLPA-LFA, Sanger sequencing, and high-resolution melting (HRM) curve analysis demonstrate a perfect agreement rate of 100%. Compared to conventional genotyping assays, this system exhibits the following advantages, including visual interpretation of results, minimal requirements for sophisticated instruments and highly skilled technicians, time efficiency, as well as low cost with a price approximately at 5 dollars. We believe that the MLPA-LFA system is a robust and versatile method with the potential to detect other SNPs related to disease susceptibility and risk, as well as drug metabolism and therapeutic effects.

Methylenetetrahydrofolate Reductase C677T (rs1801133) Polymorphism Is Associated with Bladder Cancer in Asian Population: Epigenetic Meta-Analysis as Precision Medicine Approach.

The etiology of bladder cancer remains unclear. This study investigates the impact of gene polymorphisms, particularly methylenetetrahydrofolate reductase gene (MTHFR), on bladder cancer susceptibility, focusing on the rs1801133 single-nucleotide polymorphism (SNP). A meta-analysis was conducted after systematically reviewing the MTHFR gene literature, adhering to PRISMA guidelines and registering in PROSPERO (CRD42023423064). Seven studies were included, showing a significant association between the MTHFR C677T (rs1801133) polymorphism and bladder cancer susceptibility. Individuals with the T-allele or TT genotype had a higher likelihood of bladder cancer. In the Asian population, the overall analysis revealed an odds ratio (OR) of 1.15 (95% CI 1.03-1.30; p-value = 0.03) for T-allele versus C-allele and an OR of 1.34 (95% CI 1.04-1.72; p-value = 0.02) for TT genotype versus TC+CC genotype. The CC genotype, however, showed no significant association with bladder cancer. Notably, epigenetic findings displayed low sensitivity but high specificity, indicating reliable identified associations while potentially overlooking some epigenetic factors related to bladder cancer. In conclusion, the MTHFR T-allele and TT genotype were associated with increased bladder cancer risk in the Asian population. These insights into genetic factors influencing bladder cancer susceptibility could inform targeted prevention and treatment strategies. Further research is warranted to validate and expand these findings.