Maivel H. Ghattas

Evaluation of glutathione S-transferase P1 genetic variants affecting type-2 diabetes susceptibility and glycemic control.

Introduction Type 2 diabetes mellitus (T2DM) is associated with increased production of reactive oxygen species and a reduction in antioxidant defenses leading to oxidative stress. Glutathione S-transferases (GSTs) modulate oxidative stress. The present cross-sectional study was aimed at investigating the association between the GSTP1 gene polymorphism and T2DM and to clarify their effect on the glycemic control parameters. Material and methods From the Egyptian population, we enrolled 112 T2DM patients and 188 healthy controls matched for age, sex and origin. Serum lipid profile, blood-glucose level, glycated hemoglobin (HbA1c) and body mass index (BMI) were measured. DNA was extracted from the blood samples. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure GSTP1 Ile105Val gene polymorphism of study participants. Results The frequency of the Val allele in exon 5 of the GSTP1 gene in patients with T2DM was higher than that observed in healthy controls (15.2% vs. 9.6%); the difference was considered statistically significant when compared to Ile allele carriers (p = 0.03). The presence of the GSTP1 heterozygous mutant allele Ile/Val was more common in subjects with T2DM than in the control group (30.4% and 19.2%, respectively; p = 0.02). Variation in the GSTP1 gene was associated with BMI (p = 0.02) and not associated with glycemic control parameters (fasting serum glucose and HbA1c) or smoking-related risk of T2DM. Conclusions GSTP1 gene polymorphism may play a significant role in increasing the susceptibility to and risk of T2DM and obesity regardless of smoking status and had no apparent effect on HbA1c in patients with diabetes mellitus.

MTHFR functional genetic variation and methotrexate treatment response in rheumatoid arthritis: a meta-analysis

AIM To date, functional MTHFR SNPs have been tested for their impact on low-dose methotrexate (MTX) response in small rheumatoid arthritis (RA) cohorts. We sought to test their effect in the single largest cohort studied to date, and undertook a meta-analysis utilizing stringent study inclusion criteria. MATERIALS & METHODS RA patients treated with MTX monotherapy from the Yorkshire Early Arthritis Register (YEAR) were genotyped using RFLP assays, and tested for association with treatment efficacy. Studies for meta-analysis were screened by a set of stringent inclusion criteria. RESULTS & CONCLUSION rs1801131 and rs1801133 were not associated with response to MTX in the YEAR cohort, nor did they affect the probability of achieving a low disease activity state. A meta-analysis of comparable studies found no association with these SNPs. MTHFR SNPs rs1801131 and rs1801133 are unlikely to have a clinically meaningful effect on the first 6 months of MTX treatment in early RA.

C-reactive protein 1059G/C gene polymorphism, C-reactive protein levels and acute myocardial infarction.

Aims High-sensitivity C-reactive protein (hs-CRP) is an inflammatory marker, predicting the occurrence of acute myocardial infarction (AMI). Genetic predisposition to high baseline CRP might account for a high risk of heart diseases. Our study aimed at investigating an association of CRP 1059G/C gene polymorphism with plasma CRP levels and AMI in Egyptian patients. Methods Genotypes of 150 patients with AMI and 150 healthy sex and age-matched controls were analyzed using PCR–restriction fragment length polymorphism methods. hs-CRP concentrations were assessed. Results There was no significant association between CRP 1095G/C polymorphism and AMI. However, individuals with GG genotype had significantly higher plasma CRP concentration than those with GC and CC genotypes, in both controls (3.82 ± 1.03 vs. 2.34 ± 0.7; P = 0.001) and patients with AMI (8.39 ± 2.6 vs. 6.67 ± 2.4; P = 0.005). Conclusion Our results revealed that CRP 1059G/C gene variation influences plasma CRP levels. Conversely, this polymorphism was not associated with the risk for AMI.

Association of polymorphic markers of the catalase and superoxide dismutase genes with type 2 diabetes mellitus.

Our study aims at determining whether genetic polymorphisms of catalase (CAT 1167C/T) and superoxide dismutase (SOD +35 A/C) could be associated with type 2 diabetes mellitus (T2DM). The study was conducted on 105 Egyptian patients with T2DM and 115 control subjects. Genotypes were done by polymerase chain reaction-restriction fragment length polymorphism methods. Homeostatic model assessment of insulin resistance (HOMA-IR), CAT and SOD activities, glycated hemoglobin, and insulin and lipid profiles were assessed. CAT and SOD activities were significantly decreased in T2DM compared with the control subjects. T allele of CAT and C allele of SOD1 were significant risk factors for T2DM. No effects of CAT or SOD1 gene polymorphisms on glycated haemoglobin or on HOMA-IR were found. With regard to the enzymes activities, only +35 A/C of SOD1 was related to SOD activity. Genetic variants C1167T of CAT gene and +35 A/C of SOD1 gene has no role in insulin resistance in T2DM.

Relaxin-3 is associated with metabolic syndrome and its component traits in women

OBJECTIVES Relaxin-3 was found to play a role in appetite regulation, increasing food intake and body weight. The current study aimed to investigate the relation of relaxin-3 to metabolic syndrome and its component traits in women. DESIGN AND METHODS The study was conducted on 300 female subjects, 150 healthy control and 150 metabolic syndrome patients. The component traits of metabolic syndrome were determined for all participants. RESULTS Serum relaxin-3 level was significantly higher in the metabolic syndrome patients than in the healthy control group. It was also significantly correlated with all the component traits of metabolic syndrome. CONCLUSION The results suggest that metabolic syndrome is associated with increased serum relaxin-3 levels in women. Relaxin-3 might be considered as a potential biomarker of metabolic syndrome.

Association of estrogen receptor alpha gene polymorphisms with metabolic syndrome in Egyptian women

OBJECTIVE Metabolic syndrome is a risk factor for coronary heart diseases as well as diabetes, fatty liver and several cancers. The prevalence of metabolic syndrome in women appears to be increasing, particularly in women of childbearing age. In the present study, we assessed the association of estrogen receptor-alpha gene polymorphisms (XbaI and PvuII) with metabolic syndrome and its related phenotypes. MATERIALS/METHODS One hundred and fifty Egyptian female patients with metabolic syndrome (mean age 35.52±6.86) were compared with one hundred and fifty age matched healthy Egyptian women (controls). The component traits of metabolic syndrome were determined, and the XbaI and PvuII genotypes were assessed with the PCR-RFLP method. RESULTS Our data indicated a significant difference in the allele frequencies of XbaI, but not PvuII, between the metabolic syndrome and control groups (P=0.0003 and P=0.164). Carriers of the minor alleles of XbaI and PvuII gene polymorphisms, in either the homozygous or heterozygous form, were associated with high diastolic blood pressure, high total cholesterol and LDL-c levels, increased HOMA-IR values and decreased QUICKI values compared to carriers of the major allele. However, only the minor G allele of XbaI was associated with measures of adiposity, specifically, BMI and waist circumference. CONCLUSIONS The XbaI polymorphism of the estrogen receptor alpha gene is associated with metabolic syndrome. On the other hand, PvuII gene polymorphism is not associated with the occurrence of the disease in this sample of Egyptian women.

Patterns of angiotensin converting enzyme insertion/deletion gene polymorphism among an Egyptian cohort of patients with rheumatoid arthritis.

This case control study was designed to determine the patterns of angiotensin converting enzyme insertion/deletion (ACE I/D) gene polymorphism in rheumatoid arthritis (RA) patients and healthy controls.

The Methylation Profile of IFN-γ, SOCS1 and SOCS3 Promoter Regions in End-Stage Renal Disease

End-stage renal disease (ESRD) is a state of chronic inflammation. DNA methylation is a major epigenetic modification that has the potential to silence gene expression. IFN-γ and suppressor of cytokine signaling (SOCS) are essential modulators of inflammation. The current study aimed to determine the methylation status of IFN-γ, SOCS1 and SOCS3 promoter regions in DNA isolated from peripheral blood of ESRD patients and controls, in order to correlate this methylation status with the clinical features of ESRD. Ninety six ESRD patients and 96 healthy ethnically, age and gender matched controls were included in the study. The promoter methylation of the studied genes was assessed using the methylation-specific polymerase chain reaction (MSP). Most of our samples were positive for IFN-γ promoter methylation. Full unmethylation was observed only in the ESRD group (7.3%), and statistical difference was observed among groups (P=0.02). IFN-γ unmethylation was associated to a decrease in estimated glomerular filtration rate (eGFR) and an increase in both serum creatinine and total cholesterol levels. For SOCS1 promoter methylation, partial and full methylation were observed only in ESRD patients (5.2% and 2.1%, respectively); however no methylation was detected in controls (P=0.014). SOCS3 promoter methylation was not detected in either the patient or control group. In conclusion, the methylation profile of IFN-γ and SOCS1 promoter regions play an important role in the pathogenesis of ESRD. The present study highlights the role of epigenetics in disease progression.