Influence of matrix metalloproteinase 9 variant rs17576 on ischemic stroke risk and severity in acute coronary syndrome.

BACKGROUND: Ischemic injury is a common mechanism in both ischemic stroke (IS) and acute coronary syndrome (ACS). Matrix metalloproteinase 9 (MMP-9), an endopeptidase that degrades extracellular matrix, is important in the pathogenesis of IS. The purpose of this study is to evaluate the association between the SNP rs17576 in MMP-9 gene with (1) the risk and severity of acute ischemic stroke in Saudi Arab individuals with recent acute coronary syndrome, and (2) the risk of acute coronary syndrome in Saudi Arab individuals without ischemic stroke. METHODS: A case control study of 200 IS patients, 520 ACS patients (without IS), and 500 aged-matched healthy controls were genotyped to detect the MMP-9 polymorphism rs17156. RESULTS: Our study demonstrated a non-significant difference in the genotype and allele frequencies of the MMP9 rs17576 polymorphism between the patients with IS and patients with ACS without IS (P = 0.31 for the GA genotype, 0.25 for the AA genotype and P = 0.20 for the A allele). AA genotype was found to be statistically significant between IS and control groups; [OR=1.84, 95 % CI (1.08-3.14), p =0.015]. A allele showed a significant difference between the two groups [OR=1.28, 95 % CI (1.00-1.64), p =0.028]. By comparing ACS without IS and controls, AA genotype was significant [OR=1.46, 95 % CI (1.01-2.12), p =0.029]. Stratification by NIHSS score revealed higher mortality and early neurologic deterioration in IS patients with NIHSS score ≥ 16 (p < 0.001, 0.044 respectively). CONCLUSION: We deduced the lack of association either with allele or genotype frequencies (p>0.05) between the IS cases and the cases of ACS without IS. In contrast there was a significant association of mutant genotype AA between either the IS group or ACS (without IS) group, and the control group. In addition, different rs17576 genotypes were not associated with raised mortality or a tendency to develop early neurologic deterioration.

Clinical and laboratory characteristics of multisystem inflammatory syndrome in children associated with COVID-19 in Egypt: A tertiary care hospital experience.

AIM: We aimed to evaluate MIS-C patients' clinical manifestations, laboratory test results and mortality outcomes in an Egyptian tertiary care university hospital. METHODS: We conducted a 12 month cross-sectional study in a tertiary-care university children's hospital. All paediatric patients (1 month to 16 years old) who met the CDC criteria for MIS-C were enrolled in the study. We assessed patients' clinical presentations, complications, treatments, imaging studies, laboratory test results and outcomes. The baseline clinical and laboratory findings of survivors and non-survivors were compared. RESULTS: Of 45 MIS-C patients, 24 (53.3%) were males, and the median (interquartile range) age was 4 (1.25-10) years. All patients had fever, 64.4% had respiratory manifestations, 48.9% presented with coma, 44.4% presented with shock, 33.3% presented with seizures, 31.1% had abdominal pain, 28.9% had vomiting and 22.2% presented with cerebrovascular stroke. A total of 15 (33.3%) patients died, and the non-survivors had a significantly higher incidence of respiratory manifestations (P = 0.028), shock (P = 0.034), cerebrovascular stroke (P = 0.043) and seizures (P = 0.044) as compared to the survivors. In addition, the serum levels of ferritin (P = 0.047), alanine aminotransferase (P = 0.047) and aspartate aminotransferase (P = 0.05) were significantly higher in the non-survivors as compared to the survivors. CONCLUSIONS: Based on our findings, MIS-C associated with COVID-19 is a potentially fatal illness. Hospitalised patients with MIS-C often have multi-organ injuries affecting the respiratory, cardiovascular, gastrointestinal and neurological systems. The deceased are more likely to exhibit respiratory manifestations, shock, cerebrovascular stroke, seizures and elevated serum levels of ferritin and liver enzymes.

Impact of rs599839 Polymorphism on Coronary Artery Disease Risk in Saudi Diabetic Patients.

Background: Coronary artery diseases may be affected by several genetic and nongenetic factors. Single-nucleotide polymorphism (SNP) rs599839 and type 2 diabetes mellitus (T2DM) can affect the occurrence and severity of coronary artery disease (CAD). Methods: Our aim was to investigate how T2DM and the rs599839 variant affected serum lipid levels and the degree of CAD patients' coronary artery stenosis. rs599839 polymorphism genotyping was done on Saudi patients with coronary angiography performed previously. Patients enrolled were divided into group A (360 DM patients), group B (225 DM patients with CAD), and group C (190 healthy volunteers as control). Results: Individuals with diabetes and CAD who possessed the GG genotype in rs599839 exhibited markedly reduced means of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG; 224.5, 116.2, and 221.4 versus 251.6, 131.3, and 261.7 mg/dl, p=0.003, 0.007, and 0.025, respectively) than AA genotype. The odds ratio and the confidence interval of 95% for G allele carriers of rs599839 were OR = 0.62, 95% CI: 0.41-0.82, and p=0.003, among diabetic patients with CAD. Conclusions: In patients with diabetic CAD, the locus 1p13.3 polymorphism rs599839 was found to be substantially correlated with serum lipid levels. Furthermore, among Saudi patients with diabetes, the G allele of rs599839 variant lowers the CAD risk.

Interleukin-10: Genetic association and biochemical prediction of sepsis-induced AKI in ICU critically ill patients: A cross-sectional study.

BACKGROUND: Sepsis is a potentially life-threatening condition that eventually causes multi-organ dysfunction in critically ill patients. Acute kidney injury (AKI) is a widespread and severe threatening complication of sepsis, a condition termed sepsis-induced AKI (S-AKI), with poor clinical outcomes and high mortality rates. Inflammatory and immunological responses are important variables in S-AKI. This study aimed to examine the relationship of rs1518111 polymorphism in the interleukin-10 (IL-10) gene and serum/urine IL-10 levels with sepsis-induced AKI in critically ill patients in the ICU. METHODS AND RESULTS: In this cross-sectional study, 310 critically ill adult patients were recruited, of whom, 197 developed S-AKI. Real-time PCR was performed to detect the rs1518111 polymorphism. Circulating blood and urine IL-10 levels of IL-10 were measured. For rs1518111 SNP, the presence of at least one T allele increased the risk of occurrence of S-AKI in critically ill patients with sepsis (OR: 1.34, 95% CI: 1.07-3.17; p ˂ 0.001), regardless of the type of infection and severity of sepsis. Blood and urine IL-10 levels were an excellent prediction of S-AKI (AUC: 0.881 and 0.953 and sensitivity: 90.2% and 97.6% at cutoff 133.5 and 5.67 pg/mL, respectively). Regression analysis showed that WBC count and increased blood and urine IL-10 levels, in addition to the presence of TT genotype, are independent risk factors for AKI. CONCLUSION: rs1518111 polymorphism in the IL-10 gene is a risk factor for sepsis-induced AKI in the ICU. Serum/urine IL-10 markers may be used as early predictors of S-AKI in critically ill patients with sepsis, thereby improving early management.

Coronary Artery Disease: Association Study of 5 Loci with Angiographic Indices of Disease Severity.

BACKGROUND: Different common gene variants were related to coronary artery disease (CAD) in many studies. Yet, the relation of these loci to the severity of CAD is not completely elucidated. METHODS: We enrolled 520 subjects (315 CAD cases and 205 controls). CAD presence and extension were assessed by coronary angiography (CAG). Genotyping of five SNPs (namely, rs2230806 (1051G > A) in ABCA1 on chromosome 9, rs2075291 (553G > T) in ApoA5 on chromosome 11, rs320 in LPL on chromosome 8 intron (T → G at position 481), rs10757278 (c.22114477A > G), and rs2383206 (c.22115026 A > G) on chromosome 9p21 locus) was performed by allele-specific PCR. The degree and site of arterial lesions were used to classify patients, tested for association with CAD severity, and related to allele dosage. RESULTS: The polymorphisms rs2383206 and rs10757278 showed significant associations with 2- and 3-vessel coronary disease (p =0.003 and 0.006, respectively). The homozygous GG genotypes of rs10757278 was associated with higher frequency of left anterior descending (LAD), right coronary artery (RCA) and left circumflex (LCX) diseases (p =0.002, 0.016 and 0.002, respectively). The GG genotypes of rs2383206 were found in higher percentage in patients with left main (LM) trunk and left circumflex (LCX) diseases (p = 0.013 and 0.002, respectively). CONCLUSION: SNPs rs10757278 and rs2383206 allele dosage could predict CAD severity in the Saudi Arab population.

Interferon-gamma Expression Profile as Diagnostic Signatures of Unexplained Infertility in Female Patients Suffer from Hashimoto's Thyroiditis.

Diagnosis of unexplained infertility (UEI) is made by exclusion and a relatively common problem that affects couples worldwide. Unfortunately, it is a not uncommon for females to suffer from Hashimoto's thyroiditis (HT). Interferon-gamma (IFN- γ) has a central key role in HT and in the ability to conceive. We aimed to estimate serum IFN- γ level and its expression profile in Egyptian women with HT and assess their possible association with UEI. In this study, we examined 120 women with HT. We evaluated fertility in all patients; female patients who suffer from UEI were detected. Diagnosis of HT was based on the clinical data and the laboratory measures, enzyme-linked immunosorbent assay was used to measure serum IFN- γ, and the expression of IFN-γ messenger ribonucleic acid (mRNA) was assayed by real-time polymerase chain reaction (PCR). According to the results of this study, 37.5 % of the studied females who suffered from HT were diagnosed with UEI. The serum level of IFN-γ and its gene expression showed a significant positive correlation with thyroid-stimulating hormone (TSH) and thyroid autoantibodies. However, a negative correlation was found with anti-müllerian hormone (AMH), free T4 (FT3), and free T4 (FT4). Analysis by linear regression revealed that TSH and FT3 were associated with serum level of IFN-γ; while FT3 was associated with IFN-γ gene expression. We concluded that both are valued markers in diagnosing UEI in female patients suffering from HT.

Association between HindIII (rs320) variant in the lipoprotein lipase gene and the presence of coronary artery disease and stroke among the Saudi population.

Lipoprotein Lipase (LPL) is known to be a key enzyme for lipid metabolism specifically in an enzymatic glycoprotein which provide tissues without fatty-acids and eliminates triglycerides (TG) by the circulation. Mutations in LPL were proven to cause alteration in fractions within lipoprotein, causing the development of atherosclerosis which predispose to weakening coronary artery disease (CAD) and stroke. We examined the linkage between genetic variant HindIII in LPL on lipoprotein fractions, stroke occurrences and CAD. In this case-control study, we have recruited 315 CAD cases and 205 age-matched controls. A total of 520 genomic DNA was digested with the purified PCR products for restriction fragment length polymorphism with HindIII restriction enzyme. The distribution of genotypes in a decreasing order were TT, 148 (47%), GT 135 (42.9%) and GG 32 (10.2%) in CAD groups of the study while the pattern in controls were GT 91 (44.4%), TT 86 (42%) and GG 28 (13.7%). None of all the allele or genotype frequencies were found to be significant in our study (p greater than 0.05), while the biochemical levels for both TG and LDL-c were shown to be prone in CAD patients when compare with the controls. Furthermore, the occurence of strokes were more in CAD groups vs. controls: 72 (22.9%) vs. 7 (3.4%) [p 0.000]. This could indicate the influence of HindIII variant on plasma lipid levels, and the possibility of considering it a risk factor for atherosclerosis leading to CAD and stroke occurrence.

Maternal vitamin D level and vitamin D receptor gene polymorphism as a risk factor for congenital heart diseases in offspring; An Egyptian case-control study.

Vitamin D & vitamin D receptor (VDR) signaling play a very crucial role in early embryonic heart development. We construct this case-control study to investigate the association between maternal serum vitamin D level & VDR gene Fok1 polymorphism and risk of congenital heart defects (CHD) in offspring. Fifty mothers who had term neonates with CHD were considered as cases. Fifty age-comparable healthy mothers who had neonates without CHD were contemplated as controls. Maternal serum 25 hydroxyvitamin D [25(OH) D] level was tested using ELISA. Maternal VDR gene Fok1 polymorphism was analyzed using PCR-based RFLP-assay. There was a significant decrease in maternal vitamin D level (P = 0.002) and a significant increase in vitamin D deficient status (P = 0.007) among cases when compared to controls. VDR gene Fok1 genotypes distribution frequency were in accordance with Hardy Weinberg equilibrium (HW) among controls. A significant increase in VDR gene Fok1 F/f & f/f genotypes and f allele were observed in cases compared to controls with estimated odds ratio (95% confidence interval) & P-value of 3 (1-8) & P = 0.006, 11 (1-97) & P = 0.01 and 3 (2-6) & P = 0.001 respectively. There was a significant decrease in maternal vitamin D level in neonates with cyanotic CHD (P = 0.000) compared to those with a cyanotic CHD while there was no significant difference in VDR Fok1 genotype (P = 0.18) & allele (P = 0.05) distribution between two groups. We concluded that maternal vitamin D deficiency and VDR gene Fok1 F/f, f/f genotype and f allele were associated with increased risk of CHD in offspring.