Meta Gene最新文献

Female Infertility is a serious health issue, and genetic factors plays crucial role in female infertility. To explore the molecular mechanism involved in female infertility, we had investigated demographic, clinicopathological factors and gene expression profile of BMP15 and GDF9 in primary and secondary female infertility patients. Present study comprised of 469 primary and 210 secondary infertile females, and 419 fertile females (controls). The expression level of GDF9 and BMP15 genes was studied using quantitative real-time PCR and multifactor dimensionality reduction tool (MDR) was used to detect high-risk interaction. Finding revealed that there was down-regulation of the BMP15 and GDF9 gene in both primary and secondary infertile women in comparison to fertile women. A significant difference in the expression level of GDF9 gene among the study subjects for the various levels of TSH and RBS (p < 0.01) indicating that the level of gene expression was influenced by few hormonal factors. The best risk factor model predicted for female infertility was the five-factors model of TSH, LH, LH/FSH ratio, Hb, MCV with 100% CVC and maximum TBA = 0.921 and p < 0.01. Thus, down-regulation of GDF9 and BMP15 gene and interaction of clinicopathological factors significantly persuade female infertility, and these findings might be useful as possible biomarker for the estimation of primary and secondary female infertility.

Background

Despite extensive effort, breast cancer (BC) is still among the most lethal cancer in women. Here we explored the interaction of traditional markers (including pathological, clinical and demographical parameters) associated with breast cancer and 5 genetic variants (e.g., connexin37-rs1764391; ABCB1-rs2032582; CYP1B1-rs1056836; CDKN2A/B-rsrs10811661; CDKN2A/B-rs1333049) in BC.

Methods

Forty variables from 115 patients and 230 healthy individuals (e.g., pathology [T, N, M], genes, biochemical parameters [e.g., CA153, ki_67, ER, CEA] were collected and then analyzed. For studying internal relationships of each variables and as a risk factor, the correlation matrix was used. For implementation, Python programming language 3.7.2 was utilized and the coefficient of correlation between 0.7 and 1 was considered.

Results

Our finding revealed that there is a correlation between Ki_67 and cancer_family, between PR and ER, as well as a correlation between T and P53, CA153, ER, PR and cancer_family. Moreover, our result showed a relationship between Stage with p53, PR, CA153, T and N. Similarly, there was also a correlation between the genetic variables ABCB1 and CYP1B1, CDKN2 and CYP1B1, CDKN2 and ABCB1, CYP1B1 and Connexin37, ABCB1 and Connexin37, CDKN2A and CYP1B1, CDKN2A and ABCB1. The strong correlation of variables was seen stage T N in BC. However,the good correlation of variables was seen rs1764391, Dominnt108, p53, CA153, ER and PR in BC.

Conclusion

Our data provide a novel inside on the potential values of emerging markers in combination with current traditional markers as an approach in identification of high risk breast cancer patients.

Background

Hypoxia-inducible factor-1α (HIF-1α) and its downstream gene, vascular endothelial factor (VEGF), play an important role in modulating the immune system function and consequently alternation the susceptibility to systemic lupus erythematosus (SLE) disease.

Objective

The present study aimed to investigate the effect of the HIF-1α and VEGF gene polymorphisms and the susceptibility to SLE.

Methods

The 140 patients and 150 healthy age and gender-matched people as a control group participated in the study. The PCR-RFLP method was used for genotyping.

Results

No remarkable differences in allele frequencies of HIF-1α (rs11549465) and VEGF (rs699947) were seen between the SLE and control groups. The frequencies of CT genotype of the HIF-1α (rs11549465) and CA genotype of VEGF (rs699947) in the control were significantly higher than SLE group (OR = 0.53; 95% CI = 0.32–0.53; p = 0.014; OR = 0.57;95% CI = 0.33–0.99; p = 0.046, resp.). In the case of HIF-1α (C111A) polymorphism, the CA and AA variants were not found.

Conclusion

HIF-1α (rs11549465) CT and VEGF (rs699947) CA genotypes were identified as protective factors for SLE. However, additional studies are required to confirm the association between HIF-1α and VEGF polymorphisms and SLE.

Background

In connection with the problems of infertility, one in four married couples in the world seek medical help because of the problems of the natural conception of a child. However, the biochemical and genetic mechanisms underlying male infertility are still poorly understood. This study aimed to identify a potential link between the –262C > T (rs1001179) polymorphism of the catalase (CAT) gene and pathospermia.

Methods

A total of 23 publications were analyzed up to July 2021, of which 5 case-control studies met all inclusion criteria. The analysis comprised a total of 1611 men: with pathospermia (n = 1082) and healthy donors (n = 529). Meta-analysis was performed using a “ fixed effects model” with a given OR and 95% confidence intervals for all models. The analysis of the “publication error” was carried out using the Begg and Egger tests. Then, the trial sequential analysis (TSA) was performed to assess association number of studies.

Results

Three studies have refer a correlation between the CAT-262C/C genotype and the risk of pathospermia. One study did not reveal a direct relationship between the rs1001179 polymorphism and pathospermia, and another study indicated an increased risk of pathospermia in carriers of the TT genotype. Based on the data of all analyzed studies, the odds ratio was calculated for the association of the rs1001179 polymorphism of the CAT gene with pathospermia; it was found that this value is 2.7 (OR = 0,73; 95% Cl = 0,57-0,92; p = 0.007).

Conclusion

Based on the results obtained, observed that the C-262 T locus of the CAT it is related with male infertility in various populations, but it requires more studies to confirm. As it can be assumed that the association of the CAT C262T (rs1001179) polymorphism with the development of pathospermia may vary depending on the ethnic group.

The genetic structure of the people of mainland Japan and Okinawa has been gradually unveiled in recent years. However, previous anthropological studies dealing with people in the Amami islands, located between mainland Japan and Okinawa, were less informative because of the lack of genetic data. In this study, we collected DNAs from 104 subjects in two of the Amami islands, Amami-Oshima island and Kikai island. We analyzed the D-loop region of mtDNA, four Y-STRs, and four autosomal nonsynonymous SNPs to clarify the Amami islanders' genetic structure compared with peoples in Okinawa, mainland Japan, and other regions of East Asia. We found that the Amami islanders showed a genetically intermediate position between mainland Japan and Okinawa in mtDNA and Y-STR. However, the frequencies of several autosomal SNPs in the Amami islanders indicated a significant difference from mainland Japanese, which may be because of the gene flow from Okinawa but not natural selection. Moreover, extremely high or low frequencies of several alleles implied a founder effect in Kikai islanders. Note that there is room for the interpretation of the results because of the small sample size and number of alleles in the present study. Geographically broad and detailed samplings and genome-wide analyses are awaited.

Background

Congenital hearing loss refers to prenatal hearing impairment, which is the commonly shared problem among sensory disorders that ranges from slight to profound. In this study, we screened the involvement of connexin 26 & connexin 30 gene in congenital hearing loss patients from the Kargil district of Ladakh, India by target gene sequencing.

Materials and methods

The peripheral blood sample of the patients was collected followed by DNA extraction and PCR of the target gene of interest. The amplified target gene was then sequenced and analysed for any changes in nucleotide sequence.

Results

In this study, the connexin 26 & connexin 30 are the target gene that are associated with hearing loss and in this study, we found mutations in the connexin 26 gene and none of the mutations were found in the connexin 30 gene. The mutations found in the connexin 26 gene are “NM_004004:c.71G>A, “NM_004004:c.223C>T, “NM_004004:c230G>A, “NM_004004:c.380G>A, and “NM_004004:c.439G>A which change the amino acids to W24X, R75W, W77X, R127H, and E147K respectively and the frequency of the connexin 26 mutations in patients was 23% and the overall mutations in the cohort were 14.5%. This study found that “NM_004004:c.71G>A (W24X) nucleotide variant as common mutation. Both homozygous as well as heterozygous variants were found. R127H was the only mutation observed in control samples. A significant association was seen between connexin 26 gene mutations and familial history of congenital hearing loss and consanguinity with the p-value P<0.001.

Conclusion and significance

Although the etiology has been found to be multifactorial. However, the role of any nucleotide variant in the gene of interest needs to be thoroughly investigated to study the genetic etiology of the anomalies. The results of this study showed a positive association between congenital hearing loss and the connexin 26 gene. However, we did not find any role of the connexin 30 gene in congenital hearing loss.

Background

Human T-lymphotropic virus type 1 (HTLV-1) is the main cause of adult T cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The aim of this study was to evaluate the dysregulation of immune genes that may be involved in the pathogenesis of ATLL using microarray datasets.

Method

The gene expression profiles of ATLL cases (GSE19080) were obtained from GEO database. Next, the quality and reliability of data were evaluated by MetaQC, and the expression data in each group were normalized by affy package. Subsequently, the R package MetaDE was applied for the analysis of differentially expressed genes (DEGs). Using STRING database, protein-protein interaction network (PPIN) was constructed for hub DEGs. Finally, online servers including STRING, Enrichr, and KEGG pathway were applied for gene enrichment and interpretation of the results.

Results

65 significant hub DEGs were divided in three groups, normal health, asymptomatic carrier and ATLL patients. The PPIN analysis between hub DEGs was carried out by STRING. Enrichment analysis revealed that the hub DEGs were involved in various pathways such as apoptosis, proliferation of T cell, Ras signaling, MAPK signaling, NF-κB signaling, integrin signaling, P53 signaling, angiogenesis, tissue invasion, and DNA damage process.

Conclusion

According to the present study, HTLV-1 appears to cause inflammation by enhancing cell proliferation. During the HTLV-1 infection, dysregulation of immune genes such as IL-10, TGF-β, JAK, BCL2, etc. result in immortalization of HTLV-1-infected CD4+ T cells, and eventually progression to ATLL.

Objective

Acute myocardial infarction is one of the leading causes of death in the developed countries. This study aimed to study the association between sirtuin1 (SIRT1) gene polymorphism rs7069102 and promoter variant rs12293349 of sirtuin3 (SIRT3) gene and MI.

Patients and methods

150 subjects were enrolled: 100 myocardial infarction (MI) patients and 50 healthy individuals. All subjects were investigated for blood glucose, lipid profile, cardiac markers (creatine kinase (CK-MB) and troponin I (TnI) by ELISA and genotyping of SIRT1 rs7069102 and SIRT3 rs12293349 by real time PCR.

Results

MI cases had significantly higher prevalence of SIRT1 rs7069102 GG genotype and G allele when compared to controls. GG genotype and G allele elevated the risk of MI. The dominant (CG + GG versus CC) and recessive (GG versus CC + CG) models both showed a significant difference in the distribution of rs7069102 genotypes. Under the dominant model, total cholesterol, LDLc and CK-MB levels were significantly higher in CG + GG patients. While under the recessive model, GG patients showed significantly increased FBG, 2 h PPG, HbA1c, total cholesterol, and LDLc (p = 0.001). By univariate and multivariate logistic regression analysis, LDLc and total cholesterol were the only independent determining variables. Considering the SIRT3 rs12293349, there is no significant differences between patients and controls.

Conclusion

According to the findings, carrying the variant-type G allele of the SIRT1 rs7069102 was linked to an elevated risk of MI suggesting that this genetic variation could be a promising MI marker in an Egyptian population.