Gene Reports最新文献

Background

The 11β-hydroxysteroid-dehydrogenase 1 (11β-HSD1) enzyme catalyzes the interconversion of cortisone and cortisol, with mainly oxoreductive activity in intact cells due to co-expression with hexose-6-phosphate dehydrogenase (H6PD). The uterine localization of 11β-HSD1 and its reduced placental expression in women with preeclampsia (PE) suggest a role for 11β-HSD1 in PE pathogenesis. We investigated the association of rs4844880 and rs846910 variants in the HSD11B1 gene with PE in Tunisian women.

Methods

The study cases comprised 334 women who presented with PE and 314 age-matched normotensive women who served as controls. The rs4844880 and rs846910 HSD11B1 gene variants were genotyped by real-time PCR.

Results

The rs4844880 T > A and rs846910 G > A minor allele frequencies were not different between PE cases and control women, which persisted after adjusting for age, BMI, gestational age, premature delivery, and baby weight. An association was noted for rs4844880 A/A genotype with a heightened risk of PE, which persisted after controlling key covariates. The (minor) A allele of rs4844880 was linked with elevated serum ALT and higher serum AST. In contrast, carriage of the rs846910 minor (A) allele was connected with higher baby weight on delivery and serum AST levels. Setting the major allele homozygotes (T-G) as a reference, a higher prevalence of double minor allele (A-A) haplotype was seen in PE cases than in corresponding controls, which persisted after controlling for age and BMI. Controlling for gestational age and baby weight identified the T-A haplotype and confirmed the association of the A-A haplotype with a heightened risk of PE.

Conclusion

Our results support an association between HSD11B1 polymorphisms and increased risk of PE and PE-associated clinical features.

Background

Protein convertase subtilisin/kexin type 9 (PCSK9), a key protein in lipoprotein metabolism, is a candidate gene in the genesis of cardiovascular disease. However results about its relationship with coronary artery disease (CAD) are controversials. Objectives: The objectives of the present study were: first, to investigate the association between PCSK9 polymorphism (rs7552841) and CAD for the first time in a Tunisian population, second, to explore the association between this polymorphism and cardiovascular disease biomarkers in patients with CAD. Patients & Methods: One hundred and twenty nine healthy subjects and 101 patients with CAD are included in the study. PCSK9 genotypes were determined using the PCR-RFLP method. Results: The distribution of genotypes (CC + CT vs TT) showed significant difference between control and CAD groups (p = 0.02). In patients with CAD, C allele carriers had high level of cardiac tissue biomarkers. Lactate dehydrogenase (LDH), cardiac troponin I and aspartate aminotransferase (AST) were higher in CC + CT genotypes (p = 0.008, 0.047 and 0.043 respectively). More else in CC + CT carriers total cholesterol and LDL-C concentrations were significantly higher (p = 0.043 and 0.041 respectively) than TT genotype carriers. However oxidative stress (Malondialdehyde, Conjugated Diene and Glutathione Peroxidase) and inflammation biomarkers (C - reactive protein) did not vary according to rs7552841 polymorphism. Conclusion: CAD patients carrying C allele had higher levels of tissue damage biomarkers and cholesterol compared to TT homozygous which makes them more predisposed to CAD complications. More studies are required to determine if rs7552841 PCSK9 polymorphism could be taken into consideration in secondary prevention.

The study focused on isolating thermophilic bacteria from the hot springs of Madhya Pradesh, India, with the aim of identifying strains capable of producing industrially valuable enzymes. Among the 15 isolated strains, SR-7 identified as Bacillus subtilis exhibited significant enzyme activity, leading to its selection for further investigation. Genomic analysis revealed key characteristics of SR-7, including a 3,593,163 base pair chromosome with a GC content of 44.14 %. The genome was found to contain 55 tRNA genes, four rRNA clusters, and 3744 protein-coding genes. These genes encompass essential metabolic pathways and genes responsible for thermophilic adaptation, highlighting the potential for industrial applications. Further experimentation demonstrated SR-7 have the ability to produce various enzymes of industrial significance, such as amylase, lipase, cellulase, protease, lecithinase, gelatinase, and pectinase. Importantly, enzyme production was observed across a broad pH range (6.5 to 10) and temperature spectrum, indicating the versatility and adaptability of SR-7 to different environmental conditions. The findings suggest that SR-7 holds promise as a valuable resource for the pharmaceutical and industrial sectors. Its capacity to produce thermostable enzymes suitable for a range of applications underscores its potential contribution to biotechnological processes. By harnessing the enzymatic capabilities of thermophilic bacteria like SR-7, industries can pursue more sustainable and efficient production methods, reducing reliance on traditional chemical processes and enhancing overall productivity. Further research into the enzymatic properties and genetic mechanisms of SR-7 may unveil additional avenues for its utilization in various industrial processes.

Ovarian cancer is among the most commonly diagnosed cancer in women worldwide. Multiple risk factors could be attributed to the development of this disease, thus implicating variable incidence rates worldwide. Being the sixth in incidence and fourth in mortality among all cancers in women in the Arab world, ovarian cancer should be allocated a considerable interest among the other gynecologic cancers. This review aims to project the current epidemiological perspective in this part of the world while trying to consider several factors that could explain the incidence variability between the Arab countries internally, and externally compared to the world. The screening, prognostic factors and treatment modalities that are currently adopted in different Arab countries will be also presented. Close attention is additionally paid to the remarkable genetic difference that is found in the Arab countries pool, which could also be considered as a major factor that could explain the mentioned variability. In conclusion, noticeable efforts are seen in the Arab world when it comes to ovarian cancer-related research. However, further investigations for additional risk factors should be conducted to improve the early detection of this mostly asymptomatic disease and thereby enhance the quality of life and the disease prognosis.

Triple Negative Breast Cancer (TNBC) constitutes 12–17 % of breast cancers and is distinguished by the absence of hormone receptor expression, deviating from other breast cancer types. Coupled with its elevated proliferation index, TNBC develops multidrug resistance, diminishing treatment efficacy, weakening disease prognosis, and leading to an aggressive clinical course. This study aimed to assess ABCB1, ABCC1, ABCG2, and ABCC9 gene expression, which play a primary role in the development of multidrug resistance, alongside miRNAs (miR-466, miR-4539, miR-659-3p, miR-3123, miR-3133, and miR-655-3p) targeting these genes. While ABCB1 (p = 0.433), ABCC1 (p < 0.05), and ABCG2 (p < 0.05) exhibited increased expression in tumor tissues, ABCC9 (p = 0.587) did not. miR-466 (p = 0.802), miR-4539 (p = 0.732), miR-659-3p (p = 0.807), and miR-3123 (p = 0.980) were upregulated, whereas miR-3133 (p < 0.05) and miR-655-3p (p = 0.190) were downregulated. Within the scope of our study, we also evaluated the clinical parameters like tumor size, stage, and neoadjuvant treatment that significantly impacted Progression Free Survival (PFS) and Overall Survival (OS). Considering these results, we found that the metastatic status significantly influenced PFS and OS. Chemotherapeutics were found to not affect survival times. Assessing the impact of miRNAs, which we view as potential therapeutic targets, on average survival revealed that elevated miR-3133 expression was correlated with shorter PFS and OS, whereas decreased miR-655-3p expression was associated with longer PFS and OS. In summary, the relevant miRNAs could serve as predictive biomarkers for drug response and aid in developing miRNA-targeted gene therapy strategies.

Objective

This study aims to investigate the association between Renin-angiotensin aldosterone system (RAAS) and Cytochrome P450 gene polymorphisms in hypertension patients of the South Indian population using pharmacogenomics profile.

Methods

Hypertension cases (N = 147) and control subjects (n = 150) were collected from Tamil Nadu, India. A case-control association study was conducted to assess the involvement of RAAS gene polymorphisms (REN rs397514691, REN rs544315427, REN rs567667202) and CYP gene polymorphisms (CYP2D6 rs754164689, CYP2D6 rs1058172, CYP3A4 rs765598920) in essential hypertensive patients. Genotyping was performed using the PCR-RFLP method, and significant results were validated through RT-PCR analysis.

Results

The genotype and allele distribution of REN rs397514691 and rs544315427 variants significantly associated with hypertensive patients (Variant Allele Frequency (VAF) = 0.11; VAF = 0.27, respectively). CYP2D6 polymorphisms rs754164689 and rs1058172 variant alleles were significantly associated with female hypertensive patients, suggesting a potential risk allele for essential hypertension in the South Indian population. REN and CYP3A4 variants, highly connected in pharmacology action, were validated through RT-PCR amplification studies, providing new insights into their role in the development of hypertension. Association confirmation was achieved through multifactor dimensionality reduction analysis.

Conclusion

The genes associated with specific variants, particularly REN and CYP2D6, may serve as potential markers for the early diagnosis of hypertension and as new drug targets, particularly in the female population.

Background

Cytokines and matrix metalloproteinases play an important role in inflammation and metastasis in the development of cancer. Single nucleotide polymorphisms in these genes may affect gene expression and protein activity and, therefore, may be associated with cancer predisposition. The study seeks to examine the correlation between single nucleotide polymorphisms in the cytokines (Interleukin-1α and Interleukin-12β) and Matrix metalloproteinase (MMP9) gene with oral cancer. The interplay of the genetic variants, Interleukin 1α -889 C/T (rs1800587), Interleukin 12β +1188A/B (rs3212227), and MMP9 R279Q (rs17576) with tobacco chewing and smoking habits is determined in patients with oral cancer and controls. The relationship between these genetic variations with the tumor size, lymph node involvement, and metastasis in oral cancer was studied.

Method

Case-control research was implemented with a total of 150 participants, which includes 50 individuals who were diagnosed with oral cancer and 100 healthy volunteers. The study on Single Nucleotide Polymorphism (SNP) was performed using the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) technique.

Results

Interleukin-1α -889 C/T polymorphism was significantly associated with oral cancer. The heterozygous genotype (CT) IL-1α -899 C/T was most frequent in oral cancer patients with a p value of 0.000002 in the chi-square test with no node involvement or metastasis. No interaction with the smoking or tobacco chewing habit with the genotypes of any of the genes is observed. The genotype of the mutant (TT) was also significantly different among the two groups (p = 0.01, OR = 7.63, CI- 1.5–37.5). The distribution of the mutant RR genotype of MMP9 R279Q in oral cancer patients was statistically significant in comparison with healthy controls (p = 0.005, OR = 4.46, CI- 1.52–3.04). The genotypic variants of IL-12β +1188A/B were, however, not found to be associated with oral cancer risk. IL-1α-899 (CT) and MMP9R279Q (RR) genotypes were found to be significantly associated with tumor size.

Conclusion

This finding indicates that the substitution of C to T at IL-1α-889 position and substitution of glutamine with arginine at amino acid position 279 in MMP9 due to single nucleotide polymorphism increases the risk of oral cancer. IL-12β +1188 polymorphism was not associated with oral cancer risk. Habit does not play any role in the interaction of these genes with oral cancer.

The increasing global prevalence of type 2 diabetes mellitus (T2DM) necessitates investigating its complex etiology. This study aimed to explore the relationship between exposure to toxic metals, expression of endoplasmic reticulum stress response (ERSR) genes, and various biochemical parameters, including glycated hemoglobin (HbA1c), insulin resistance (HOMA-IR)/sensitivity (QUICKI), lipid profile, and estimated glomerular filtration rate (eGFR) in T2DM patients. T2DM patients and control subjects were matched for age, gender, and lifestyle factors. Biochemical parameters, toxic metal levels, and ERSR gene expression were analyzed using inductively coupled plasma mass spectrometry (ICPMS) and quantitative reverse transcription PCR (qRT-PCR), respectively. T2DM patients exhibit dysregulated lipid profiles and significantly higher fasting blood sugar (FBS), HbA1c, and insulin levels (all p < 0.0001). The insulin sensitivity was lower in T2DM patients (0.32 ± 0.09) than in the control group (0.35 ± 0.02, p = 0.02). Insulin resistance was significantly higher in the T2DM group (5.38 ± 3.15) than in the control group (1.98 ± 0.86, p = 0.0001). Nickel (4.75 ± 2.45 ppb, p < 0.0001) and arsenic (1.85 ± 1.78 ppb, p < 0.0001) levels were significantly elevated in T2DM patients. There was significant upregulation of ER stress genes: GRP78, CHOP, IRE1, ATF4, ATF6, and XBP1 (all p < 0.0001), while PERK was significantly down regulated (0.68-fold, p < 0.0001). Nickel levels were positively correlated with HOMA-IR (r = 0.49, p < 0.0001) and HbA1c (r = 0.35, p = 0.002). Arsenic levels were correlated with insulin (r = 0.34, p < 0.0001), insulin resistance (r = 0.51,p < 0.0001), HbA1c (r = 0.53, p < 0.0001), Arsenic levels (β = 0.37, p < 0.001), XBP1 (β = 0.36, p < 0.0001) independently associated with HbA1c.This study has revealed a significant association between arsenic exposure and the upregulation of XBP1 at the onset of T2DM. The overexpression of XBP1 and high levels of arsenic were independently associated with HbA1c and insulin resistance.

Background

Triple-negative breast cancer (TNBC), an aggressive subtype with a poor prognosis, is notably difficult to treat. Emerging research highlights the significant roles of long non-coding RNAs (lncRNAs) in cancer biology. LncRNAs, such as NALT1 and CTBP1-AS1 are implicated in oncogenic processes; this study hypothesizes that NALT1 and CTBP1-AS1 are overexpressed in TNBC tissues compared to adjacent non-tumor tissues and may serve as biomarkers. Methods: One hundred pairs of tumor and adjacent non-tumor tissues were obtained from female patients with triple-negative breast cancer. After extracting RNA, cDNA synthesis was carried out for all samples. Quantitative real-time PCR (qRT-PCR) was employed to assess differential gene expression. Results: The expression of NALT1 (p-value <0.0001) and CTBP1-AS1 (p-value <0.0002) lncRNAs increased in TNBC tumor tissues in comparison to adjacent non-tumor tissues. A statistically positive correlation (ρ = 0.5844, p < 0.0001) was observed between the expression levels of NALT1 and CTBP1-AS1 in breast cancer patients. The ROC analysis indicated that NALT1 (AUC = 0.718, specificity = 61 %, sensitivity = 70 %) shows moderate potential and CTBP1-AS1 (AUC = 0.648, specificity = 65 %, sensitivity = 55 %) exhibits poor potential as a diagnostic biomarker for breast cancer. Conclusion: This study shows that NALT1 and CTBP1-AS1 lncRNAs are upregulated in TNBC tissues. Additionally, a positive correlation exists between their expression levels in breast cancer. Further research is needed to understand their mechanisms as molecular biomarkers.