The c.-190 C>A transversion in promoter region of protamine 1 gene as a genetic risk factor in Egyptian men with idiopathic infertility.

Protamines are considered the most important structure in the sperm nucleus, and they are proteins with a significantly large amount of amino acids carrying a positive charge, which allows the formation of the tight package of the genomic DNA in the spermatozoa. Many authors studied the abnormalities in the protamine 1 (PRM1) and/or protamine 2 (PRM2) genes and reported their possible association with male infertility. The chromosome 16 (16p13.2) carries these genes containing multiple undiscovered single nucleotide polymorphisms. The aim of the present study was to investigate the association of c.-190 C>A transversions that occur in PRM1 with idiopathic infertility in a sample of Egyptian men. It was a case-control study, and blood samples were collected from sixty male patients complaining of idiopathic infertility and forty healthy fertile males. The c.-190 C>A transversion in promotor region protamine 1 gene (rs2301365) was assessed by 5' nuclease assay, using Rotor-Gene Q real-time PCR system. The results of the present study revealed that CA and AA genotypes in PRM1 gene were associated significantly with low sperm concentration and decreased sperm motility (p = 0.001). Cases carrying A allele had a 6.05-fold increased risk for idiopathic infertility than cases carrying the C allele (OR: 6.05, 95% CI: 2.038-17.98 p statistically significant ≤0.05). Analysis of the results revealed that the c.-190 C>A transversion may be involved in the development of male infertility.

Plasma long non-coding RNA HOTAIR as a potential biomarker for gastric cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) Hox transcript antisense intergenic RNA ( HOTAIR) has been suggested to be implicated in gastric cancer tumorigenesis and progression; however, little is known about the role of the plasma HOTAIR in gastric cancer diagnosis and prognosis. OBJECTIVE: The current study was aimed at investigating the clinical relevance of plasma long non-coding HOTAIR as a non-invasive diagnostic biomarker in gastric cancer. METHODS: Plasma HOTAIR expression was measured in 50 patients with newly diagnosed gastric cancer and 50 age- and sex-matched healthy controls using quantitative reverse transcription polymerase chain reaction. RESULTS: Plasma level of HOTAIR was significantly higher in gastric cancer patients compared with healthy controls ( P < 0.001). By using receiver operating characteristic curve analysis, it was found that plasma HOTAIR could diagnose gastric cancer with 88% sensitivity and 84% specificity. Furthermore, increased HOTAIR expression was associated with advanced tumor stages, higher grades, and metastasis. CONCLUSION: Plasma HOTAIR might serve as a potential non-invasive biomarker for diagnosis of gastric cancer.

Mitochondrial DNA copy number variation as a potential predictor of renal cell carcinoma.

BACKGROUND: Peripheral blood mitochondrial DNA (mtDNA) copy number alteration has been suggested as a risk factor for several types of cancer. The aim of the present study was to assess the role of peripheral blood mtDNA copy number variation as a noninvasive biomarker in the prediction and early detection of renal cell carcinoma (RCC) in a cohort of Egyptian patients. METHODS: Quantitative real-time polymerase chain reaction (qPCR) was used to measure peripheral blood mtDNA copy numbers in 57 patients with newly diagnosed, early-stage localized RCC and 60 age- and sex-matched healthy individuals as a control group. RESULTS: Median mtDNA copy number was significantly higher in RCC cases than in controls (166 vs. 91, p<0.001). Increased mtDNA copy number was associated with an 18-fold increased risk of RCC (95% confidence interval: 5.065-63.9). On receiver operating characteristic curve analysis, it was found that mtDNA could distinguish between RCC patients and healthy controls, with 86% sensitivity, 80% specificity, 80.3% positive predictive value and 85.7% negative predictive value at a cutoff value of 108.5. CONCLUSIONS: Our results showed that increased peripheral blood mtDNA copy number was associated with increased risk of RCC. Therefore, RCC might be considered as part of a range of potential tumors in cases with elevated blood mtDNA copy number.

Study of the role of tumor necrosis factor-α (-308 G/A) and interleukin-10 (-1082 G/A) polymorphisms as potential risk factors to acute kidney injury in patients with severe sepsis using high-resolution melting curve analysis.

RATIONAL: Septic acute kidney injury (AKI) is a prevalent complication in intensive care units with an increased incidence of complications. OBJECTIVE: The aim of the present study was to assess the use of high-resolution melting curve (HRM) analysis in investigating whether the genetic polymorphisms; -308 G/A of tumor necrosis factor-α (TNF-α), and -1082 G /A of Interleukin-10 (IL-10) genes may predispose patients diagnosed with severe sepsis to the development of AKI. METHODS: One hundred and fifty patients with severe sepsis participated in the present study; only sixty-six developed AKI. Both polymorphisms were studied using HRM analysis. MAIN FINDINGS: The low producer genotype of both studied polymorphism of TNF-α and IL-10 genes was associated with AKI. Using logistic regression analysis, the low producer genotypes remained an independent risk factor for AKI. A statistically significant difference was detected between both studied groups as regards the low producer genotype in both TNF-α (-308 G/A) and interleukin-10 (IL-10) (-1082 G/A) polymorphisms being prevalent in patients developing AKI. Principle conclusions: The low producer genotypes of both TNF-α (-308 G/A) and IL-10 (-1082 G/A) polymorphisms could be considered a risk factor for the development of AKI in critically ill patients with severe sepsis, thus management technique implemented for this category should be modulated rescuing this sector of patients from the grave deterioration to acute kidney injury. Using HRM for genotyping proved to be a highly efficient, simple, cost-effective genotyping technique that is most appropriate for the routine study of large-scale samples.