Association between Apo B, LDL-R and PCSK9 gene polymorphisms with coronary artery diseases in Egyptians.

BACKGROUND: Many studies have focused on the significance of lipid regulatory genes in the pathophysiology of Coronary artery disease (CAD). ApoB XbaI (rs693) and EcoRI (rs1042031) single nucleoid polymorphisms (SNPs) were investigated to detect whether they are risk factors for CAD. Till now, this association remains uncertain. SMARCA4 (rs1122608) SNP has directly related to dyslipidemia. Loss of function mutations (LOF) in PCSK9 result in a reduction in LDL cholesterol and are associated with protection from the development of CAD. METHODS: This study was conducted on 54 CAD patients who were admitted at Internal Medicine Specialized Hospital (Cardiology Department) and 47 healthy controls. Peripheral blood samples were taken from both groups. DNA was extracted from EDTA-blood samples, then PCR- RFLP for ApoB XbaI (rs693) and EcoRI (rs1042031), SMARCA4 (rs1122608) and PCSK9 (rs505151) SNPs was done. RESULTS: No statistically significant difference was found between patients and controls as regard EcoRI SNP. XbaI (rs693) X + X + genotype was significantly higher in control group (P = 0.0355). SMARCA4 (TT, GT + TT) genotypes, and T allele (P < 0.001); PCSK9 AG genotype and G allele (P = 0.027 and 0.032 respectively) were more frequent in CAD patients than controls. CONCLUSION: SMARCA4 (rs1122608) and PCSK9 (rs505151) SNPs are significantly accompanying with the risk of CAD development in the Egyptian population. X + X + genotype appeared to have a protective effect against CAD. However, no observed association between EcoRI (rs1042031) and the risk of CAD development was found.

Interferon-induced transmembrane protein 3 in hepatocellular carcinoma patients.

OBJECTIVE: The study aimed to investigate the over expression of IFITM3 in hepatocellular carcinoma Egyptian patients. BACKGROUND: Hepatocellular carcinoma (HCC) continues to be a serious disease burden. Interferon Induced Transmembrane protein 3 (IFITM3) is a protein that encoded in humans by the IFITM3 gene. It plays a critical role in the immune system's defense, responsible for a large portion of the antiviral activity. In this study, we showed that IFITM3 rs 12252-CC was over expressed in HCC patients compared to control group with HCV infection. METHOD: DNA sequencing was applied for detection of IFITM3 rs 12252-CC and IFITM3 protein level was measured by ELISA to 50 patients with HCC with cirrhosis and 50 with Hepatitis C virus infection. RESULTS: The obtained results of this study indicated that IFITM3 rs 12252-CC was significantly elevated in HCC group, the codominant model of CC genotype of IFITM3 gene had high association with risk of hepatocellular carcinoma with odd ratio (OR) = 2.70, p = 0.041. CONCLUSION: IFITM3 play an important role in progression of hepatocellular carcinoma. Results revealed that IFITM3 rs 12252-CC among Hepatocellular carcinoma patients would allow diagnosis and starting intervention.

Relationship between interferon-induced transmembrane protein 3 and matrix metalloproteinase-9 gene polymorphisms in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma originates from hepatocytes as a result of the effects of numerous genetic variations. Interferon-Induced Transmembrane protein 3 (IFITM3) is involved in the processes of cellular differentiation, apoptosis, cell adhesion, and immune cell regulation. Matrix Metalloproteinase-9 (MMP-9) are zinc dependent endopeptidases that cleave extracellular matrix contents and play an important role in the progression of cancer. OBJECTIVE: The study aimed to outline the key molecular biology progression in hepatocellular carcinoma and the relationship between hepatocellular cancer and genetic polymorphisms of IFITM3 and MMP-9. METHODS: In total 200 patients with hepatocellular carcinoma patients (n=100) and a control group with Hepatitis C virus (n=100) which collected randomly from the EL-Mansoura oncology center during the interval between June 2020 and October 2021. The expression of MMP-9 and the IFITM3 SNP was investigated. MMP-9 gene polymorphisms were estimated by using PCR-RFLP and IFITM3 gene was detected using DNA sequencing, ELISA was used to measure protein levels of MMP-9 and IFITM3. RESULTS: The T allele of MMP-9 was more frequent among patients (n=121) than control subjects (n=71). The C allele of IFITM3 was more frequent among patients (n=112) than control subjects (n=83), polymorphisms of the genes linked to a high risk of disease development, patients of MMP-9 (TT genotype), odd ratio (OR) = 2.63, IFITM3 (CC genotype), OR= 2.43. CONCLUSIONS: We found that the genetic polymorphisms of MMP-9 and IFITM3 are related to the occurrence and development of hepatocellular carcinoma. This study might be utilized in clinical diagnosis and therapy and to provide a baseline for prevention.

Serum uric acid/creatinine ratio and free androgen index are synergistically associated with increased risk of polycystic ovary syndrome in obese women.

BACKGROUND: Features of metabolic syndrome such as abdominal obesity, insulin resistance, hypertension and dyslipidemia are commonly encountered in polycystic ovary syndrome (PCOS). Recent evidence has suggested an association between high serum uric acid/creatinine (UA/Cr) ratio and metabolic syndrome however, no studies have investigated this association in PCOS. The current study was conducted to investigate the relationship between UA/Cr ratio and PCOS and to identify whether UA/Cr ratio and free androgen index (FAI) have an additive interaction for detection of PCOS risk in obese women. METHODS: This study enrolled 40 obese women with PCOS and 40 control women with regular menstrual cycles matched for age and body mass index (BMI). Anthropometric measurements, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipids profile, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), total testosterone, free androgen index (FAI), UA/Cr ratio were assessed. RESULTS: Serum UA/Cr ratio was significantly higher in obese women with PCOS than in non-PCOS women. UA/Cr ratio was correlated with BMI, waist and neck circumferences, blood pressure, fasting insulin, HOMA-IR, lipids, LH/FSH, estradiol, DHEAS, total testosterone, FAI and SHBG. UA/Cr ratio and FAI were independent risk factors for PCOS in obese women however, the addictive interaction between UA/Cr ratio and FAI had a higher fold risk (OR: 4.3, 95% CI, 3.4-7.58) and a more significance (P = 0.002) for determination of PCOS. CONCLUSION: Serum UA/Cr ratio combined with FAI can exert an additive or synergistic impact on prediction of PCOS in obese women.

Association Between Total Bilirubin Levels and Cardio-Metabolic Risk Factors Related to Obesity.

BACKGROUND: The link between bilirubin and cardiometabolic outcomes has been previously identified with positive health effects of mild hyperbilirubinaemia. On the other hand, recent evidence has suggested an association between low circulating bilirubin levels and obesity. This study was conducted to assess the association of total bilirubin levels with metabolic and cardiovascular risk factors related to obesity. METHODS: A total of 50 obese adults and 50 healthy controls matched for age and sex were enrolled in this study. Anthropometric measurements, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), HOMA- ß (%), lipids profile, monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), uric acid, gamma glutamyl transpeptidase (GGT), AST/ALT ratio and total bilirubin were assessed. RESULTS: Total bilirubin, high density lipoprotein cholesterol (HDL-C) and AST/ALT ratio were significantly lower, whereas fasting insulin, HOMA-IR, total cholesterol, triglycerides, low density lipoprotein cholesterol, NLR, uric acid and GGT were significantly higher in obese adults than in healthy controls. Bilirubin was negatively associated with body mass index, waist circumference, fasting insulin, HOMA-IR, NLR, PLR, uric acid, and positively associated with HDL-C. HDL-C and NLR were the independent predictor variables of total bilirubin. CONCLUSION: Among all the studied cardio-metabolic risk factors, HDL-C and NRL are the most closely associated variables with total bilirubin levels in obese adults.

Serum Paroxonase 1 level may be an Indicator and Predictor of the Severity of Androgenetic Alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is a common stressful form of hair loss caused by androgen excess, genetic factors, and exposure to oxidative stress (OS) with the formation of reactive oxygen species (ROS). Paraoxonase 1 (PON1) is an enzyme synthesized in the liver bound to high-density lipoproteins to prevent lipid peroxidation. AIM: The aim of our work is to estimate serum PON1 level in patients with AGA and correlate its levels with disease severity which may help in determining if there is a role of ROS in pathogenesis of AGA. SUBJECTS AND METHODS: This study was carried out as a case and control on 40 patients with AGA (diagnosed by typical clinical and dermoscopic finding) versus 40 control subjects. Blood samples were taken from all subjects to assess serum PON1enzyme using enzyme-linked immunosorbent assay kits. RESULTS: There was a significant decrease in serum PON1 concentration level in AGA patients in comparison to controls, in addition, there was a significant decrease correlated with AGA severity (P < 0,001). The study proved that PON1 is considered highly sensitive and specific for AGA cases and a good predictive factor of AGA in healthy subjects. CONCLUSION: This is the first study done to reveal that the level of PON1 significantly decreased in AGA patients, which may give additional proof that OS has role in the pathogenesis of AGA and hence may help in the management of AGA by adding antioxidants in treatment.