Meta Gene最新文献

P-element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a newly known class of small non-coding RNAs with 24–31 nucleotides in length. There are more than 20,000 piRNA genes in the human genome and some of them have a role in cancer. In this study, we investigated the expression of piRNAs in acute myeloid leukemia (AML). We used publicly available small RNA sequencing data derived from the peripheral blood of patients with AML and control samples to be re-analyzed for investigation of piRNA expression pattern and then was validated via the real-time polymerase chain reaction (PCR). Differential expression analysis showed that four upregulated piRNAs and six downregulated piRNAs in AML samples, among which, the piR-32,877 and piR-33,195 were the top two upregulated piRNAs. Real-time PCR was performed to validate the increased expression of these two piRNAs in AML compared to controls. Pathway analysis was also performed. The results provide evidence that piR-32,877 and piR-33,195 may serve as a new diagnostic and prognostic biomarker in AML.

Background

Proprotein convertase subtilisin/kexin type 9, a member of the serine protease family, plays an important role in the regulation of plasma low density lipoprotein cholesterol by stimulating the degradation of LDL receptor.

Method

In this meta-analysis, we explored the correlation of PCSK9 polymorphisms E670G and D374Y with the elevated plasma lipid levels, which leads to a condition known as hypercholesterolemia, by calculating the standardized mean difference and Odds Ratio with 95% confidence interval. The statistical analysis was done using SPSS version.

Results

Under dominant genetic model, pooled results had shown that PCSK9 E670G polymorphism was associated with higher LDL-C levels among the Asians (SMD = 0.53; I² = 40%; OR = 0.7610; 95% CI = 0.6554 to 0.8837 and p value = 0.003).

Conclusion

The close relationship between both polymorphisms of PCSK9 gene i.e. E670G and D374Y, with the elevated plasma LDL-C levels has been observed. E670G polymorphism is highly prevalent among the Asian population.

Background

Vitiligo is a complicated disorder identified by advanced degeneration and loss of melanocytes. Some of the main factors that cause vitiligo are cytotoxicity, autoimmunity, along with several genetic factors.

Aim

The current study aims at evaluating the association of TNFAIP3 rs6920220 and DEFB1 rs1800972 gene polymorphisms as risk factors of non-segmental vitiligo in Egyptian patients.

Patients and methods

This study was conducted on 125 patients with non-segmental vitiligo and 110 age and gender-matched healthy controls. Genotyping of TNFAIP3 rs6920220 and DEFB1 rs1800972 polymorphisms were analyzed by TaqMan probe-based real-time PCR.

Results

Significant differences in the genotypes and alleles distributions of both polymorphisms were detected between patients and controls. The AA and GA genotypes of TNFAIP3 rs6920220 increase the risk of vitiligo with OR 4.422 and 1.863 respectively. The (GA + AA) model reported risk with OR 2.016 compared to the GG genotype. The CG, GG genotypes compared to the CC genotype of DEFB1 rs1800972 were found to have an increased risk of vitiligo with OR1.7 and 2.865 respectively. The (GG+ CG) model had OR 1.856. The AA genotype, the A allele of TNFAIP3 rs6920220, the GG genotype, and the G allele of DEFB1 rs1800972 were more frequent in patients with the progressive course and those with a positive family history of other autoimmune diseases as compared to controls.

Conclusion

TNFAIP3 rs6920220 and DEFB1 rs1800972 polymorphisms could participate in the pathogenesis of vitiligo and might be considered as potential risk factors for vitiligo.

Background

Ovarian cancer (OCa) is the most lethal gynecologic cancer in women. Genes involved in the synthesis of estrogen and its polymorphisms might have an influence on OCa. The current study aimed to examine the association of selected polymorphisms of CYP17A1, CYP19A1, and HSD17B1 genes in the South Indian population with OCa. We examined single nucleotide polymorphisms (SNPs) in the CYP17A1 (rs743572), CYP19A1 (rs10046), and HSD17B1 (rs605059) genes in South Indian women with OCa (n = 200) and age-matched controls (n = 200).

Methods

All samples were genotyped using TaqMan allelic discrimination assay for all three polymorphisms.

Results

The study revealed significant increase of CC genotype (OR = 3.93; 95%CI = 1.86–8.28; p ≤0.001) and C allele frequency (OR = 1.68; 95%CI = 1.25–2.26; p ≤0.001) of rs743572 polymorphism, and CT genotype (OR = 1.61; 95%CI =1.06–2.43; p = 0.023) and T allele frequency (OR = 1.46; 95%CI =1.07–1.98; p = 0.015) of rs10046 polymorphism in OCa patients in comparison with controls. Furthermore, for rs743572 polymorphism, dominant and recessive models and the dominant model of the rs10046 polymorphism revealed a significant association with OCa risk. Additionally, the rs743572, and rs10046 polymorphisms were associated with clinical characteristics of OCa.

Conclusion

The results of the current study indicated an association between CYP17A1 and CYP19A1 gene polymorphisms and the progression of OCa and the HSD17B1 gene polymorphism did not show any association with OCa risk. However, studies on different populations with a larger number of sample sizes are needed to support the conclusions.

Background

The purpose of the present study was to perform a high-resolution melting (HRM) analysis to discover mutations in gene exons 5–8 of tumor protein p53 (TP53), as well as the relationships of these mutations to clinical parameters in prostate cancer (PC).

Methods

Genomic DNA was extracted from 50 formalin-fixed paraffin-embedded (FFPE) tissues with PC. Mutations in exons 5 and 8 of TP53 were analyzed using the HRM method. Sanger sequencing was used to describe mutations.

Results

According to the HRM analysis results, 21 (42%) PC samples had different normalized and shifted melting curves from other samples. Mutations in TP53 exons 5 and8 were observed in 12 (24%) patients by the Sanger method. The detection sensitivity of the HRM method in exon 5 and exon 8 mutations was 66.7% and 50%, respectively. PSA levels of PC patients with TP53 mutation were found to be lower than that of patients with no mutation (p = 0.8270). However, we did not find any correlations between TP53 mutations and clinical parameters (p > 0.05).

Conclusions

HRM analysis is a simple, rapid, and efficient mutation-scanning method for known/unknown mutations in TP53 exons 5and8, as well as an attractive method for detection of mutations and their analysis in FFPE tissues. Additional studies with larger patient populations are warranted to confirm the correlation between the TP53 mutations and PC risk.

Background

Breast cancer (BC) is one of the most common causes of cancer death globally, with a 0.5% increasing incidence per year. Natural killer cells (NK) have a crucial function in immune surveillance mechanisms, which recognize class I human leukocyte antigen (HLA) molecules, expressed on the target cells, through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). Impaired NK cell anti-tumor immunity has particular relevance with BC progression and metastases. KIRs are the most polymorphic receptors of NK cells that modulate NK cell activity against malignant cells through their interactions with their cognate HLA ligands.

Materials and methods

Considering this issue, we conducted this study to survey the impact of HLA class I variegation on the susceptibility to the development of BC in Kermanshahi women. In our study, the presence of HLA-C1 and HLAC2 allotypes, HLA-B Bw4 and Bw6 dimorphism, as well as HLA-A Bw4 group, were detected using polymerase chain reaction with sequence-specific primers in 52 patients with breast cancer living in Kermanshah province (Iran) and 40 healthy subjects.

Results

Here, we found that the presence of HLA-C1 allotype and HLAC1/HLAC2 genotype was significantly reduced in breast cancer patients compared to the healthy controls (P = 0.041, P = 0.005 respectively). No significant differences were found for HLA-C2, HLA-B Bw4 groups, HLA-B Bw6, and HLA-A Bw4, as well as their genotype.

Conclusion

Our results indicated the protective role for HLA-C1allotype and HLAC1/HLAC2 genotype in healthy subjects compared to patients with breast cancer.

Background

Portal hypertension is the pathophysiological process associated with the occurrence of portosystemic collaterals and usually ends with the development of Esophageal varices (EVs). Early detection helps to avoid or delay variceal bleeding. This disease is related to increased oxidative stress in the liver. One of the antioxidant enzymes that guard cells against damage from this stress is Heme oxygenase-1 (Hmox1). This study aimed to assess the reliability of single nucleotide polymorphism (SNP) in (Hmox1) (rs2071746) as a noninvasive approach for predicting the development of EVs and its importance for proper interpretation in clinical practice.

Methods

50 cirrhotic patients with esophageal varices and 50 cirrhotic patients without varices were enrolled in this study. Laboratory assesment, ultrasound, and endoscopy were done. They were genotyped for Hmox1 (rs2071746) by TaqMan allele discrimination real-time PCR on a Rotor-Gene System.

Results

Patients with esophageal varices had statistically significant lower platelet count and platelets count / splenic diameter ratio, and higher portal vein diameter than those without EVs. T allele frequency was higher in Patients with varices than those without (P-value= 0.03). Carrying TT genotype of Hmox1promotor had 13.5fold increased risk for esophageal varices development than carrying AA genotype.

Conclusion

T allele in Hmox1 SNP (rs2071746) gene could be a useful predictor of EVs presence in cirrhotic patients. Hmox1 is a promising genetic factor that influence the development and the grade of EVs in cirrhotic patients. It can also be used in prediction and risk stratification of such patients.

Background

Several polymorphisms in ERAP1 gene has been reported to be associated with psoriasis in several different populations.

Objective

To better understand the association between ERAP1 and psoriasis in Chinese Han population.

Methods

Seven SNPs (rs27044, rs27043, rs26510, rs469758, rs30378, rs30186 and rs2303208) in ERAP1 gene were genotyped in an independent cohort of 5414 patients and 5556 controls in the Chinese Han population.

Results

Six SNPs reached the genome wide significance in the combined analysis of exome, targeted sequencing and replication data with the most significant SNP as rs27044 (P_Rep = 9.92× 10⁻⁹, P_Meta = 4.05× 10⁻²⁰). Further haplotype analysis identified 11 haplotypes associated with psoriasis, in which the 2 most significant haplotypes, GCCACT (P = 7.09 × 10⁻²³) and AGTGGC (P = 3.95 × 10⁻²²) were found only in psoriatic cases. Moreover, 2 associated haplotypes were both common in both case and control cohorts, in which ACTGCT showed protective effect (P = 9.64 × 10⁻¹⁰, OR = 0.84) and GGCAGC showed risk effect (P = 1.38 × 10⁻³, OR = 1.10).

Conclusion

Our study further reveals the important roles of ERAP1 gene in the pathogenesis of psoriasis, The combination of the haplotypes will be potentially useful in providing information for determining the prediction for the development of psoriasis.

Endometrial cancer (EC) is the second most common cancer in women. A large number of human cancers exhibit dysregulation of microRNA expression including EC. MiR-15b/16–2 is one of the best-known miRNA clusters that is expressed in many types of cancer tissues. Herein, we analyzed the expression of individual miR-15b/16–2 cluster members, its paralogues, and their target network analysis, as well as their prognostic significance in EC. UALCAN and GEPIA2 were used to analyze the expression of the individual members of the cluster. The gene target was predicted through miRTarBase, and the genes were then compared through the TCGA-UCEC dataset. The differential gene expression and network analysis identified 175 DEGs associated with critical cancer-related pathways. The prognostic significance and metastatic prediction were carried out using GEPIA2 and HCMDB tools. In UCEC patient samples, miR- 15b/16–2 cluster expression is negatively correlated with the overall survival of the patients. The uterus-specific miRNA-lncRNA, miRNA-circRNA, and miRNA-sncRNA networks of miR- 15b/16–2 cluster contain 1164 edges and nodes consisting of 5 sncRNA, 124 circRNA, and 1552 genes. The DEGs analysis led to the identification of SIPA1L2, PDCD1, CCNJ, ENTPD7, PLEKHA5, NPAS3, DPH5, BTF3, NPAS3, SENP2, and CCND3 as a significant predictor of overall survival in UCEC patients. The analysis of metastasis found 24 genes significantly associated with brain and lymph node metastasis. The analysis of drug-gene interactions revealed 267 FDA-approved drugs for treating cancers. Our data provided novel insight on the miR-15b/16–2 cluster role in EC and prioritized the findings for experimental verification. Besides, more comprehensive clinical and mechanistic studies are needed to confirm our findings in endometrial cancer.

Background

Body composition and obesity is one of the major health related risk factors leading to increased metabolic mortality and morbidity. The Association of genetic polymorphism with obesity and body composition is one way to assess the health status of a given population. In Indian region of east and north east, population-based studies have been conducted to assess the relation of body composition and obesity with gene polymorphism known to be associated with obesity and cardiovascular health and disease.

Methods

The current study consisted of different ethnic groups of Eastern and North Eastern part of India. A total of 225 randomly selected apparently healthy unrelated (free from any major diseases) adult individuals of 12 Ethnic groups were selected for the present study. Kurmi, Bhumij and Bouri population of Purulia District, and Bengali population of Kolkata, West Bengal, Meitei population of Manipur, Kolui, Riang, Rupini, Chakma and Tripuri of Tripura, Santal and Sabar population of Jharkhand, India were incorporated in the present study. FTO, ACE3, PSD3 and A604G genotyping by Restriction Fragment length Polymorphism (RFLP) was performed to study specific Single Nucleotide Polymorphism (SNP) among the population. Anthropometric and socio demographic data were collected from all the subjects as per standard procedure. Overweight and obese categories for BMI classification was determined using classifications based on BMI, WC, WHR, WSR and BF percentage.

Results

The genetic polymorphism studied showed no significant relation among any of the 4 gene polymorphism with body composition variables. Smaller insignificant fraction of polymorphism for ACE, FTO gene was observed in population 3. PSD3 and A604G and polymorphism was not observed in any of the population studied.

Conclusion

Comparison of the results from anthropometric, physiological, metabolic data on the basis of body composition and gene polymorphism indicated that the studied population of twelve ethnic groups might not be susceptible to ACE, FTO, PSD3 and A604G associated obesity related disease.