Meta Gene最新文献

Introduction

Alzheimer's disease (AD), as a neurodegenerative disease, is the most common reason for dementia in the elderly. ATP- binding cassette transporter 1 (ABCA1) is a cell membrane transporter protein which is involved in cholesterol efflux. The aim of this study is to evaluate the correlation between polymorphisms of G/A (rs2230806) in ABCA1 gene with sporadic Alzheimer's disease in the southwest of Iran.

Methods

This case-control study was conducted in 180 subjects, including 100 sporadic AD patients and 80 healthy subjects. Genotypes of all samples were determined using the PCR–restriction fragment length polymorphism (PCR–RFLP) technique.

Results

The analysis of the R219K Polymorphism of ABCA1 gene indicated that there was no significant distinction between AD patients and controls. In this study when groups were stratified by age and sex, results showed that in the control group with less than 75 years, the risk of developing AD was significantly lower than subjects who were older than 75 years (P = 0.019, OR = 0.46, 95% CI = 0.24–0.88). A significant difference was detected in the risk of AD between patient and control in females older than 75 years (P = 0.028).

Conclusion

The results of this study confirm that aging is an important risk factor for AD. Also, it has been found that AD is more prevalent in women compared to men. However, our results do not support the hypothesis that R219K polymorphism in the rs2230806 region of the ABCA1 as a genetic risk factor for developing AD in our study population.

Objective

To study the association and epistatic interactions of cluster of differentiation 14 (CD14) and mannan-binding lectin 2 (MBL2) gene polymorphic variants in Indian patients with chronic periodontitis (CP).

Design

We enrolled a total of 242 individuals (121 patients and 121 control subjects), age 35 to 60 years both irrespective of gender and identified CD14 (−159C > T, NC_000005.10:g.2569190:C > T) and MBL2 (codon 52, C > T, NM_000242:c.52C > T) polymorphic variants in peripheral blood samples. We also performed epistatic interaction analysis using multifactor dimensionality reduction (MDR) approach and predicted ribonucleic acid (RNA) structure of MBL2 gene using Genebee online RNA tool.

Results

Significantly increased frequency of ‘CT' heterozygote and variant allele ‘T' in chronic periodontitis patients was observed for both CD14 and MBL2 gene polymorphisms. MDR analysis showed approximately two-fold increased risk of CP. In silico analysis showed lack of transcription factor ETF (TEA domain family member 2) binding-site in presence of ‘T' allele ‘in CD14 (-159C > T) polymorphism. The secondary RNA structure prediction of MBL2 (codon 52, C > T) polymorphism showed structural variations having approximately similar free energies.

Conclusions

A dominant effect of genotype ‘CT' heterozygote and variant ‘T' allele observed for both CD14 and MBL2 gene polymorphisms in patients with CP. The presence of ‘T' allele also results in lack of transcription factor binding site at CD14 (-159C > T) and changes in arrangements of RNA molecules that may further affect expression of CD14 and MBL2 genes leading to increased susceptibility to CP pathogenesis.

Stunting defined as anthropometrically as height-for-age Z-score (HAZ) with less than 2 standard deviation (SD) has been observed more prevalent in children in developing countries that reflect the linear growth failure. It was estimated that the prevalence of stunting in Asian countries ranges from 30% - 69%. Stunting occurs due to the interplay of genetic and environmental factors. The susceptible genes involve in hormone signalling, paracrine factor, matric molecules, intercellular pathways and cellular processes of epiphyseal growth plate. Many genetic studies conducted among stunted children has elucidated the role of genes in affecting the attribute factors such as low birth weight, socio-economy, poor preventive health care and others. Whole genome sequencing revealed potential putative genes which involve in different pathways in related to retarded epiphyseal growth plate in various Asian countries such GHSR, GH1, GHRHR, STAT5B, IGF1, COMP and many more associated genes. The data emphasize that these potential genetic markers may provide better treatment in targeting the related pathophysiology in stunting development. In this current national implementation, genetic testing has not yet been permeated to the clinical practice for a standard evaluation since lack of genetic studies on stunting genes conducted in Asian countries, particularly Malaysia.

Background

Bipolar I disorder (BID) is a severe psychiatric disease with a confirmed strong hereditary pattern. However, the genetic component is not completely clear to design the diagnostic tests. In this pilot study, we aimed to evaluate the association of haplotypes, including four polymorphisms in the IL-1 region, with BID in a sample of the Iranian population.

Methods

In a case-control study, genotyping of 95 subjects (48 BID and 47 healthy samples) were performed using PCR-based methods for IL-1α (rs1800587), IL-1b +3954 (rs1143634), IL-1b −511 (rs16944) and IL-1RN (VNTR; rs2234663) loci. PHASE was used for haplotyping, and data were analyzed using SPSS 16.

Results

Out of 55 haplotypes and 121 diplotypes, three haplotypes including two SNPs (C-T of rs1800587-rs16944, p = 0.007, T-C of rs1143634-rs16944, p = 0.044 and T-A1 of rs16944-rs2234663, p = 0.030) and one haplotype including three SNPs (C-C-T of rs1800587-rs1143634-rs16944, p = 0.012) and one diplotype including two SNPs (C-T/C-T of rs1800587-rs16944, p = 0.032) were identified to be associated with the risk of the disease. In addition, several haplotypes and diplotypes were associated with the disease's features, including the age of onset, the type of first episode and the history of depressive episodes.

Conclusion

Our findings suggest a diagnostic role of the interleukin-1 region in the BID. The risky haplotypes may carry one or more susceptibility alleles, and the evaluation of their action will aid individual-level risk prediction.

Personalized medicine is one of the popular approaches in biological sciences. Due to the great attention in personalized medicine, there exists a need for health decision algorithms developed through high-level programming languages that already compromised the statistical analyses and numerical computations. Here, we present a tool that enables us to facilitate making research in the PubMed database by classifying the scientific literature from the published abstracts and then performed the comparative analysis to highlight the importance of gene-variant relationships in the decision steps. After retrieving related genes from literature, we performed pathway analysis with them by using computer-based tools to differentiate these sub-pathways in cardiomyopathy disease that are listed as hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathy. Then, the pathogenic variants existing in these genes at each sub-pathway are retrieved, and the mechanistic interpretation about them has been gained to explain more about the differences in genes' mode of action. Lastly, the need of structure-based studies to explain the etiology of the disease has been emphasized by providing the protein structures of related genes as a guide. This study presents the importance of combining the text-mining approach with the bioinformatics tool in effective manner both for catching up with the updated literature and for revealing newly identified genes or pathways.

Alzheimer's disease (AD) is considered a progressive and devastating neurodegenerative disorder which primarily effects elders. Due to the course of the disease and the involvement of different gene loci with complex genetic studies, it is possible to calculate the relative risk of individuals at risk. In this study, our aim was to investigate the serum transcript levels of candidate microRNAs (miRNAs), including miR-138, miR-128, and miR-107 in patients with AD and compared with that of normal individuals. In this research work, during the diagnosis process of AD, 50 blood samples were obtained from patients and 50 samples were collected from healthy individuals. Then total RNA of each sample was extracted and the expression levels of miRNAs were measured by Real-time PCR method. Our analysis indicated that the relative expression of all three miRNAs decreased in AD patients compared to the healthy samples. There was statistically significant in transcript levels of miR-138 (P = 0.047) and miR-107 (P = 0.004), while the levels of miR-128 had no significant difference between two groups (P = 0.075). The receiver operating characteristic (ROC) curve analysis indicated the potential of all miRNAs as biomarkers in AD. In conclusion, miR-138 and miR-107 can be used as a diagnostic or predictive biomarker in AD. In the case of miR-128, more research is needed. We suggest further studies and evaluation of changes in the expression of these miRNAs in larger populations.

Cancer is the second leading global health burden in terms of incidence and mortality. The association between IL-6 rs2069840 variant and cancer risk has been evaluated previously by genome-wide association studies and case-control studies, but the results remained controversial. Our present meta-analysis aimed to reveal the association of IL-6 rs2069840 polymorphism with cancer risk for the first time. Review Manager 5.4 software was used for performing the meta-analysis, and heterogeneity was assessed using I². A total of 13 retrospective studies with 22,487 cases and 26,540 controls were selected for performing this meta-analysis. Our study showed that rs2069840 is not significantly associated with overall cancer risk. After stratification with population subgroups, no relationship was observed in Asians, Caucasians, Africans, or mixed populations. Subgroup analyses based on the cancer types revealed a significant correlation of rs2069840 with breast cancer in COD3 (OR = 1.13, p = 0.008), RM (OR = 1.10, p = 0.023), and OD (OR = 0.94, p = 0.029). A significant correlation was also found in COD1 (OR = 1.08, p = 0.020) and OD (OR = 1.07, p = 0.022) models for the development of other cancers (multiple myeloma, prostate cancer, gastric cancer). The findings of the present study suggest that IL-6 rs2069840 polymorphism is not linked with overall cancer risk. However, this polymorphism may be associated with breast cancer, multiple myeloma, prostate cancer, and gastric cancer.

Aim

This meta-analysis aimed to evaluate the association between different VEGF gene polymorphisms (VEGF 2578 C/A, VEGF 936 C/T, VEGF 634 G/C, VEGF 460 T/C and VEGF 405 C/G).

Methodology

Meta-analysis was performed by collecting the results of 24 appropriate studies that were retrieved from PubMed central, Embase and Google Scholar. The statistical analyses were performed by using Review Manager 5.4 software.

Results

The Meta analysis results revealed that there is no significant association between VEGF 2578 C/A, VEGF 460 T/C, VEGF 634 G/C, and 405 G/C gene polymorphisms with the risk of breast cancer. Additionally, a significant association was identified in VEGF 936 C/T polymorphism with risk of breast cancer. No publication bias was observed.

Conclusion

The results revealed that VEGF 2578 C/A, VEGF 460 T/C, VEGF 634 G/C, 405 G/C gene polymorphisms were not associated with the risk of breast cancer whereas VEGF 936 C/T polymorphism maybe associated with breast cancer. Further well deliberated studies with bigger sample size are essential to evaluate the associations.

Objective

Polycystic ovary syndrome(PCOS) is a chronic systemic disease with a multifactorial etiology resulting from complex interactions of environmental and genetic factors rather than a local disease. There are recently identified several abnormalities related to the hemostatic and fibrinolytic systems. Therefore, the study is performed to investigate the association between plasminogen activator inhibitor-1(PAI-1) -844G > A rs2227631 polymorphism and risk of PCOS.

Subject and methods

Two hundred fourteen voluntary premenopausal women (104 healthy controls and 110 PCOS patients) of similar age were included in the study. All volunteers underwent a physical examination and biochemical hormonal evaluation. PAI-1-844G > A rs2227631 variant was analysed using polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP) method. Women were diagnosed with PCOS according to the criteria of the Androgen Excess-PCOS Society.

Results

In PAI-1-844G > A, “A” additive model, AG vs. GG (OR: 2.6; 95%Cl: 1.09–6.17 p = 0.94) or AA vs. GG (OR: 2.3; 95%Cl: 0.87–5.96 p = 0.094) genotype increased the PCOS risk almost 2.5-fold. “G” dominant model, AG + GG vs. AA (OR: 0.97; 95%Cl: 0.52–1.81 p = 0.93) was not associated with PCOS risk. “G” recessive model, GG vs. AG + AA genotype reduced the risk of PCOS 2.6-fold (OR: 0.39; 95%Cl: 0.17–0.93 p = 0.033). “A” dominant model, AG + AA vs. GG genotype increased the risk of PCOS 2.5-fold (OR: 2.5; 95%Cl: 1.08–5.83 p = 0.033).

Conclusion

The rs2227631 is related to PCOS risk in Turkish Women. The study indicated that the “AA” genotype was correlated with an increased risk of PCOS while the “GG” genotype reduced the PCOS risk in Turkish women.

Objectives

Prostate cancer is the most frequent non-cutaneous malignancy in men. Numerous genetic factors play a crucial role in the progression of prostate cancer. This study was undertaken to reveal the correlation of TP53 rs1042522 and CDH1 rs16260 polymorphisms with the risk of prostate cancer in the Bangladeshi population.

Materials and methods

We recruited 210 prostate cancer patients and 210 healthy controls for the investigation. Genotyping was conducted using the PCR-RFLP technique.

Results

In case of TP53 gene rs1042522, the association analysis revealed that all genetic models were linked with significantly increased risk for prostate cancer development (CG vs. CC: OR = 1.99, p = 0.001; GG vs. CC: OR = 4.82, p < 0.00; CG vs. CC + GG: OR = 1.52, p = 0.041; CG + GG vs. CC: OR = 2.44, p < 0.00; GG vs. CC + CG: OR = 3.64, p = 0.00; G vs. C: OR = 2.32, p < 0.00). Again, the second variant rs16260 in CDH1 gene also showed significantly enhanced association in all genetic models for the development of prostate cancer (CA vs. CC: OR = 2.20, p < 0.00; AA vs. CC: OR = 2.77, p = 0.012; CA vs. CC + AA: OR = 1.98, p = 0.001; CA + AA vs. CC: OR = 2.29, p = 0.00; A vs. C: OR = 1.99, p < 0.00) except the AA vs. CC + CA model.

Conclusions

Our study indicates a significant association of TP53 rs1042522 and CDH1 rs16260 polymorphisms with increased prostate cancer risk in the Bangladeshi population. However, replication studies are required in different populations to validate our findings.