Association of TRPV5, CASR, and CALCR genetic variants with kidney stone disease susceptibility in Egyptians through main effects and gene-gene interactions.

Kidney stone disease (KSD) represents an urgent medical problem because of increasing its prevalence. Several functional polymorphisms in genes involved in the renal handling of calcium were associated with KSD pathogenesis. Among those, the rs4236480 of transient receptor potential vanilloid member 5 (TRPV5) gene, the rs1801725 of calcium-sensing receptor (CASR) gene, and the rs1801197 of calcitonin receptor (CALCR) gene appear to be of great importance. Due to the scarce data on the Egyptians, this study aimed to evaluate the association of these candidate genetic variants with the risk of developing KSD in an Egyptian population. To do so, the biochemical parameters were measured along with the genotyping of the three polymorphisms using allelic discrimination assay in 134 KSD patients and 86 age and sex-matched healthy subjects. The results showed that the genotypic distributions and allelic frequencies of the studied variants were significantly different between cases and controls. The three polymorphisms increased the risk of KSD significantly under all the tested genetic models (OR ranges from 2.152 to 5.994), except for the recessive model of the CALCR rs1801197 polymorphism after Bonferroni correction. The gene-gene interaction analyzed by multifactor dimensionality reduction selected the three-locus combination as the best model associated with the susceptibility to KSD with OR 9.706. Further, synergistic interactions were identified between TRPV5 rs4236480 and CALCR rs1801197 variants and CASR rs1801725 and CALCR rs1801197 variants. In conclusion, the TRPV5 rs4236480, CASR rs1801725, and CALCR rs1801197 polymorphisms showed a significant association with the risk of KSD in the Egyptian population. Furthermore, their complex interactions might have an impact on the genetic susceptibility to develop KSD.

Sensitivity and specificity of microRNA-204, CA125, and CA19.9 as biomarkers for diagnosis of ovarian cancer.

BACKGROUND: Ovarian cancer is usually detected at later stages and no effective screening approach, has been identified. Therefore, sensitive and specific biomarkers for detecting ovarian cancer are urgently needed. OBJECTIVE: This study aimed to investigate the efficacy of six biomarkers for the early clinical diagnosis of ovarian cancer. SUBJECTS & METHODS: The study included 120 patients (benign ovarian tumors and early and late ovarian carcinoma) and 30 control healthy volunteers. MiRNA-204, CA125, CA19.9, hepcidin, microfibril-associated glycoprotein 2, and ferroportin levels were determined in all patients and control volunteers. RESULTS: The combined area under the receiver operating characteristic curves for miRNA-204, CA125, and CA19.9 were 0.938, 1.000, and 0.998 for benign tumors and early and late ovarian carcinomas, respectively. The sensitivities of miRNA-204, CA125, and CA19.9 were 98.04%, 100.00%, and 96.19% and the specificities were 58.33%, 62.50%, and 57.78%, respectively. CONCLUSION: The positive predictivity of miRNA-204, CA125, and CA19.9 for ovarian cancer is high (59.57%, 58.24%, and 61.67%, respectively). Thus, the combination of these three biomarkers is a good diagnostic tool for ovarian cancer.

Redox dysregulation, immuno-inflammatory alterations and genetic variants of BDNF and MMP-9 in schizophrenia: Pathophysiological and phenotypic implications.

BACKGROUND: Although a clear mechanism underlying the pathophysiology of schizophrenia (SZ) remains elusive, oxidative stress, inflammatory syndrome and immune activation have become an attractive hypothesis for explaining the pathophysiology of SZ. Data from prior studies on the role of matrix metalloproteinase 9 (MMP-9) and brain-derived neurotrophic factor (BDNF) single nucleotide polymorphisms (SNPs) in SZ are contradictory. We aimed to investigate whether oxidative stress, inflammatory and immune activation markers as well as MMP-9 levels may be implicated in SZ pathogenesis. The association of MMP-9 and BDNF SNPs with the clinical expression of SZ was examined. SUBJECTS AND METHODS: Ninety-four subjects were recruited, including 44 SZ patients and 50 healthy controls. Serum levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), nitrite, C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), Beta-2 microglobulin (Β2M), complement component 3 (C3), C4 and MMP-9 were measured. The MMP-9 -1562C>T and BDNF196G>A SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism assay. Psychopathology was assessed using the positive and negative syndrome scale (PANSS). RESULTS: SZ patients showed significantly higher TBARS, PCC, nitrite, CRP, IL-6, TNF-α, Β2M, C3 and MMP-9 levels than controls. In distinguishing SZ patients from healthy controls, CRP and MMP-9 yielded similar discriminatory performance, and both perform better than IL-6, Β2M, C3, nitrite, TBARS, PCC, TNF-α and C4. The MMP-9 -1562C>T SNP genotypes distribution didn't differ significantly between controls and SZ patients. As compared to controls, SZ patients harbor a significantly higher frequency of the BDNF196GG genotype and a lower frequency of the BDNF196GA/AA genotype. Patients carrying the MMP-9 -1562CC or BDNF196GG genotype revealed a significantly higher PANSS than those carrying MMP-9 -1562CT/TT or BDNF196GA/AA genotype. Male gender and the MMP-9 -1562CC genotype were identified as independent predictive factors for higher PANSS. CONCLUSIONS: Redox dysregulation and alterations in the immuno-inflammatory pathways are major culprits in the pathogenesis of SZ. MMP-9 and BDNF SNPs are associated with the clinical phenotype of SZ and, thus, may be a useful marker predicting the phenotypic expression and prognosis of SZ patients.

Presepsin is an early monitoring biomarker for predicting clinical outcome in patients with sepsis.

Despite their undoubted helpfulness in diagnosing sepsis, increased blood C-reactive protein (CRP) and procalcitonin (PCT) levels have been described in many noninfectious conditions. Presepsin is a soluble fragment of the cluster of differentiation 14 involved in pathogen recognition by innate immunity. We aimed to investigate the diagnostic and prognostic performance of presepsin in comparison to PCT and CRP in patients presenting with systemic inflammatory response syndrome (SIRS) and suspected sepsis. Seventy-six subjects were enrolled in this study, including 51 patients with SIRS as well as 25 healthy subjects. Plasma presepsin, PCT and CRP levels were serially measured on admission and at days 1, 3, 7 and 15. Presepsin and PCT yielded similar diagnostic accuracy, whereas presepsin performed significantly better than CRP. Presepsin and PCT showed comparable performance for predicting 28-day mortality, and both biomarkers performed significantly better than CRP. In septic patients, presepsin revealed earlier concentration changes over time when compared to PCT and CRP. Presepsin and PCT could differentiate between septic and non-septic patients with comparable accuracy and both biomarkers showed similar performance for predicting 28-day mortality. Early changes in presepsin concentrations might reflect the appropriateness of the therapeutic modality and could be useful for making effective treatment decisions.

Secreted Phosphoprotein 1 Promoter Genetic Variants Are Associated with the Response to Pegylated Interferon α Plus Ribavirin Combination Therapy in Egyptian Patients with Chronic Hepatitis C Virus Infection.

BACKGROUND/AIMS: The T-helper 1 (TH1) immune reaction is essential for the eradication of hepatitis C virus (HCV) during pegylated interferon α (PEG-IFN-α)- and ribavirin (RBV)-based therapy in chronic HCV patients. Secreted phosphoprotein 1 (SPP1) was shown to be a crucial cytokine for the initiation of a TH1 immune response. We aimed to investigate whether SPP1 single nucleotide polymorphisms (SNPs) may influence sustained virological response (SVR) rates. METHODS: Two SNPs in the promoter region of SPP1 at the -443 C>T and -1748 G>A loci were genotyped in 100 patients with chronic HCV genotype 4 infection using a TaqMan SNP genotyping assay. RESULTS: Sixty-seven patients achieved a SVR, and 33 patients showed no SVR. Patients carrying the T/T genotype at the -443 locus showed a significantly higher SVR rate than those carrying the C/T or C/C genotype (83.67% vs. 50.98%, p<0.001). At the -1748 locus, the SVR rate was significantly higher in patients with the G/G genotype than in those with the A/A genotype (88.89% vs. 52.63%, p=0.028) and in patients with the G/A genotype than in those with the A/A genotype (85.29% vs. 52.63%, p=0.001). CONCLUSIONS: SPP1 SNPs at -443 C>T and -1748 G>A loci may be useful markers for predicting the response to PEG-IFN-α-2b plus RBV therapy in Egyptian patients with chronic HCV genotype 4 infection.