The Relation of VEGFA, VEGFR2, VEGI, and HIF1A Genetic Variants and Their Serum Protein Levels with Breast Cancer in Egyptian Patients.

Breast cancer is the most common type of cancer in Egyptian females. Polymorphisms in the angiogenesis pathway have been implicated previously in cancer risk and prognosis. The aim of the current study was to determine whether certain polymorphisms in the genes of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial growth inhibitor (VEGI), and hypoxia-inducible factor-1α (HIF1A) associated with breast cancer development. The study included 154 breast cancer patients and 132 apparently healthy age-matched females as a control group. VEGFA rs25648 genotyping was performed using (ARMS) PCR technique; while VEGFR2 rs2071559, VEGI rs6478106, and HIF-1α rs11549465 were genotyped by the PCR-RFLP method. Serum levels of VEGF, VEGFR2, VEGI, and HIF1A proteins in breast cancer patients and controls were measured by ELISA. There was a significant association between the VEGFA rs25648 C allele and breast cancer risk (OR 2.5, 95% CI 1.7-3.6, p < 0.001). VEGFA rs25648 C/C genotype was statistically significantly higher in breast cancer patients vs. control (p < 0.001). Participants with the T/T and T/C VEGFR2 rs2071559 genotypes had 5.46 and 5 higher odds, respectively, of having breast cancer than those with the C/C genotype. For the VEGI rs6478106 polymorphism, there was a higher proportion of C allele in breast cancer patients vs. control (p = 0.003). Moreover, the C/C genotype of VEGI rs6478106 was statistically significantly higher in breast cancer patients vs. control (p = 0.001). There was no significant difference in genotypes and allele frequencies of HIF1A rs11549465 polymorphism between breast cancer cases and control individuals (p > 0.05). Serum levels of VEGFA, VEGI, and HIF1A were considerably greater in women with breast cancer than in the control (p < 0.001). In conclusion, the genetic variants VEGFA rs25648, VEGFR2 rs2071559, and VEGI rs6478106 revealed a significant association with increased breast cancer risk in Egyptian patients.

Empagliflozin suppresses hedgehog pathway, alleviates ER stress, and ameliorates hepatic fibrosis in rats.

Worldwide mortality from hepatic fibrosis remains high, due to hepatocellular carcinoma and end stage liver failure. The progressive nature of hepatic fibrosis from inflammation to cicatrized tissues warrants subtle intervention with pharmacological agents that hold potential. Empagliflozin (Empa), a novel hypoglycemic drug with antioxidant and anti-inflammatory properties, has lately been proposed to have additional antifibrotic activities. In the current study, we examined the antifibrotic effect of the Empa through modulating the activity of hepatic stellate cells by hedgehog (Hh) pathway. We also assessed the markers of inflammatory response and endoplasmic reticulum (ER) stress. Male Albino rats were treated with either CCl4 (0.4 mg/kg twice/week) and/or Empa (10 mg/kg/day) for eight weeks. In this study, CCl4 rats had active Hh signaling as indicated by overexpression of Patched 1, Smoothened and Glioblastoma-2. CCl4 induced ER stress as CHOP expression was upregulated and ERAD was downregulated. CCl4-induced inflammatory response was demonstrated through increased levels of TNF-α, IL-6 and mRNA levels of IL-17 while undetectable expression of IL-10. Conversely, Empa elicited immunosuppression, suppressed the expression of Hh markers, and reversed markers of ER stress. In conclusion, Empa suppressed CCl4-induced Hh signaling and proinflammatory response, meanwhile embraced ER stress in the hepatic tissues, altogether provided hepatoprotection.

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.

Nano-melatonin and-histidine modulate adipokines and neurotransmitters to improve cognition in HFD-fed rats: A formula to study.

The established correlation between obesity and cognitive impairment portrays pharmacological products aimed at both disorders as an important therapeutic advance. Modulation of dysregulated adipokines and neurotransmitters is hence a critical aspect of the assessment of in-use drugs. At the cellular level, repairments in brain barrier integrity and cognitive flexibility are the main checkpoints. The aim of this study was to investigate whether melatonin and histidine, alone or in combination, could produce weight loss, meanwhile improve the cognitive processes. In this study, obese rat model was established by feeding high fat diet (HFD) composed of 25% fats (soybean oil) for 8 weeks, accompanied by melatonin (10 mg/kg), histidine (780 mg/kg), and combination of both in conventional form and nanoform. At the end of the study, adiposity hormones, neuronal monoamines and amino acids, brain derived neurotrophic factor (BDNF) and zonula occluden-1 (ZO-1) were assessed. HFD feeding resulted in significant weight gain and poor performance on cognitive test. Coadministration of histidine in the nanoform increased the level of ZO-1; an indicator of improving the brain barrier integrity, along with adjusting the adipokines and neurotransmitters levels, which had a positive impact on learning tasks. Cotreatment with melatonin resulted in an increase in the level of BDNF, marking ameliorated synaptic anomalies and learning disabilities, while reducing weight gain. On the other hand, the combination of melatonin and histidine reinstated the synaptic plasticity as well as brain barrier junctions, as demonstrated by increased levels of BDNF and ZO-1, positively affecting weight loss and the intellectual function.

Integrating experimental model, LC-MS/MS chemical analysis, and systems biology approach to investigate the possible antidiabetic effect and mechanisms of Matricaria aurea (Golden Chamomile) in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a heterogeneous disease with numerous abnormal targets and pathways involved in insulin resistance, low-grade inflammation, oxidative stress, beta cell dysfunction, and epigenetic factors. Botanical drugs provide a large chemical space that can modify various targets simultaneously. Matricaria aurea (MA, golden chamomile) is a widely used herb in Middle Eastern communities for many ailments, including diabetes mellitus, without any scientific basis to support this tradition. For the first time, this study aimed to investigate the possible antidiabetic activity of MA in a type 2 diabetic rat model, identify chemical constituents by LC-MS/MS, and then elucidate the molecular mechanism(s) using enzyme activity assays, q-RTPCR gene expression analysis, network pharmacology analysis, and molecular docking simulation. Our results demonstrated that only the polar hydroethanolic extract of MA had remarkable antidiabetic activity. Furthermore, it improved dyslipidemia, insulin resistance status, ALT, and AST levels. LC-MS/MS analysis of MA hydroethanolic extract identified 62 compounds, including the popular chamomile flavonoids apigenin and luteolin, other flavonoids and their glycosides, coumarin derivatives, and phenolic acids. Based on pharmacokinetic screening and literature, 46 compounds were chosen for subsequent network analysis, which linked to 364 candidate T2DM targets from various databases and literature. The network analysis identified 123 hub proteins, including insulin signaling and metabolic proteins: IRS1, IRS2, PIK3R1, AKT1, AKT2, MAPK1, MAPK3, and PCK1, inflammatory proteins: TNF and IL1B, antioxidant enzymes: CAT and SOD, and others. Subsequent filtering identified 40 crucial core targets (major hubs) of MA in T2DM treatment. Functional enrichment analyses of the candidate targets revealed that MA targets were mainly involved in the inflammatory module, energy-sensing/endocrine/metabolic module, and oxidative stress module. q-RTPCR gene expression analysis showed that MA hydroethanolic extract was able to significantly upregulate PIK3R1 and downregulate IL1B, PCK1, and MIR29A. Moreover, the activity of the antioxidant hub enzymes was substantially increased. Molecular docking scores were also consistent with the networks' predictions. Based on experimental and computational analysis, this study revealed for the first time that MA exerted antidiabetic action via simultaneous modulation of multiple targets and pathways, including inflammatory pathways, energy-sensing/endocrine/metabolic pathways, and oxidative stress pathways.

Role of heme oxygenase-1, cytokines, and vascular endothelial growth factor in murine Schistosoma mansoni.

OBJECTIVES: Among tropical diseases, schistosomiasis caused by Schistosoma mansoni is the second major cause of morbidity and mortality worldwide. Inflammation was considered as an adverse event that contributes to the pathology associated with schistosomiasis. Heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) have been implicated in the process of angiogenesis. The current study aimed to evaluate the effect of S. mansoni infection on HO-1 gene expression, IL-4, IL-12, and VEGF to address the role of these factors in the pathogenesis of schistosomiasis. METHODS: Thirty mice divided equally into three groups comprised a non-infected control group and two S. mansoni-infected groups. Infected animals were studied at 8 and 12 weeks post-infection. Serum IL-4, IL-12, and VEGF were measured. HO-1 mRNA was detected by RT-PCR of liver homogenates and HO activity was assessed as percentage of carboxy hemoglobin. RESULTS: S. mansoni-infected mice showed a progressive increase in serum IL-4 and VEGF and decrease in IL-12 levels. In addition, HO-1 expression and activity were increased in infected mice compared to control group with the maximum increase at egg deposition stage. CONCLUSION: Our results suggested that the body response to acute stage of S. mansoni infection by elevating the expression of the stress gene HO-1 and that VEGF may serve as a new indicator of progression of S. mansoni associated angiogenesis which regulates granuloma and/or fibrosis development in the liver of infected mice. Understanding the role of HO-1 and VEGF in pathogenesis of S. mansoni may provide a new pharmacological target.

Relation of locus 1p13 rs646776 polymorphism with the risk of preeclampsia.

OBJECTIVE: This study aimed to assess the relation of locus 1p13 rs646776 (T/C) polymorphism with preeclampsia in Egyptian women. METHODS: The study included 100 healthy pregnant female subjects and 100 preeclampsia patients. The genotypes of the polymorphisms were assessed. Endothelin-1 level was determined in plasma. RESULTS: The major T allele of the 1p13.3 genomic region rs646776 polymorphism had a higher frequency in preeclampsia patients. Carriers of C allele had significantly lower endothelin-1 levels, lower systolic and diastolic blood pressure, decreased proteinuria, and increased HDL-C in the patients. CONCLUSION: The rare C allele of rs646776 polymorphism in chromosomal locus 1p13.3 is associated with decreased risk of preeclampsia.

Pre-micro RNA-499 Gene Polymorphism rs3746444 T/C is Associated with Susceptibility to Rheumatoid Arthritis in Egyptian Population.

Pre-miRNA-499 gene is associated with autoimmune disease. Mir-449 rs3746444 polymorphism is inconsistent for rheumatoid arthritis (RA). This study aimed to investigate association of mir-499 rs3746444 polymorphism with RA activity and severity in Egyptian population. The study population was conducted as case control study in 100 RA patients diagnosed according to the American College of Rheumatology classification criteria for RA, and the control group included 100 healthy subjects who were age-and sex-matched to the RA group. Different genotypes were assessed using polymerase chain reaction-restriction fragment length polymorphism. 95% Confidence interval and odds ratio were defined to assess the strength of association. Regarding patients, thirty-three patients carried TT genotype, fifty-three patients carried TC genotype and fourteen patients carried CC genotype. So the frequency of the minor C allele in RA patients was significantly higher than the control subjects (P = 0.037). TC, CC genotypes and C allele frequencies were significantly associated with disease severity as they had high rheumatoid factor (55.78 µIU/ml) and anti-cyclic citrullinated peptide (Anti-CCP) antibody (297.32 µIU/ml). Moreover, the heterozygote TC had more severe and more active form of the disease compared with homozygote CC or TT as they had high Anti-CCP antibody, and disease activity score 28 (score 5). Our work suggests that C allele of Pre-miRNA rs3746444 polymorphism contributes to heritability of susceptibility to RA compared to T allele. This polymorphism was associated with the activity and severity of the disease.

Association of interleukin-1A insertion/deletion gene polymorphism and possible high risk factors with non-alcoholic fatty liver disease in Egyptian patients.

CONTEXT: Interleukin-1A (IL-1A) is a cytokine involved in inflammatory process. IL-1A (rs3783553) gene polymorphism is comprised in the regulation of IL-1A expression. OBJECTIVE: This study aims to evaluate association of IL-1A (I/D) gene polymorphism with NAFLD and its component traits among Egyptian populations. METHODS: The study included 75 healthy subjects and 75 patients with NAFLD. Different genotypes of IL-1A (I/D) gene polymorphism were determined by PCR-PAGE technique, serum IL-1A level and other biochemical parameters were measured. RESULTS: The major D allele was significantly associated with NAFLD patients (p = .002). DD genotype showed a significant increase in BMI and decrease in HDL-C. Also serum IL-1A was significantly correlated with the DD genotype. Serum IL-1A showed a significant positive correlation with BMI, triglycerides, total cholesterol, LDL-C, VLDL-C and FBG, and a significant negative correlation with HDL-C. CONCLUSIONS: Major D allele of IL-1A (I/D) gene polymorphism is associated with NAFLD in the Egyptian population.

Cytotoxic T-lymphocyte-associated protein 4 gene polymorphism is related to rheumatoid arthritis in Egyptian population.

CONTEXT: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a CD28-family receptor expressed on T-cells which suppresses T cell proliferation. CTLA-4 -318C/T polymorphism is involved in regulation of CTLA-4 expression. OBJECTIVE: The study aimed to investigate the genetic association of CTLA-4 -318C/T polymorphism with rheumatoid arthritis (RA) and the activity and severity of the disease in the Egyptian population. METHODS: A single nucleotide polymorphism (rs5742909) in CTLA-4 was genotyped in 100 RA patients and 100 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. Diagnostic tests were measured for RA patients. RESULTS: The frequency of T allele in RA patients was significantly higher than in the control subjects (p = 0.002). CT and TT genotypes had high C-reactive protein, erythrocyte sedimentation rate and disease activity score 28 while CC genotype had a high rheumatoid factor. CONCLUSION: A minor allele of CTLA-4 rs5742909 polymorphism was associated with RA and the activity but not the severity of the disease.

Intestinal fatty acid binding protein Ala54Thr polymorphism is associated with peripheral atherosclerosis combined with type 2 diabetes mellitus.

BACKGROUND: Intestinal fatty acid-binding protein 2 (FABP2) is expressed in enterocytes and binds saturated and unsaturated long-chain fatty acids. The FABP2 Ala54Thr polymorphism has been reported to effect lipid metabolism. The aim of the present study was to assess the relationship between this polymorphism and peripheral atherosclerosis combined with type 2 diabetes mellitus (T2DM) in an Egyptian population. METHODS: The study was performed on 100 T2DM patients with peripheral atherosclerosis and 100 control subjects. The Ala54Thr polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism, whereas serum FABP2 levels were determined using ELISA. Fasting blood glucose, fasting serum insulin concentrations, HbA1c, lipid profile, body mass index (BMI) and systolic and diastolic blood pressure (SBP and DBP, respectively) were determined. RESULTS: There was a higher frequency of the Thr54 allele among the patient group (P = 0.002). In Ala54/Thr54 heterozygotes and carriers of the rare Thr54/Thr54 genotype, there were significant increases in BMI and FABP2. Those with the Thr54/Thr54 genotype had significantly decreased high-density lipoprotein cholesterol (HDL-C) concentrations; in addition, those with the Thr54/Thr54 genotype had significantly higher SBP and DBP than subjects with the Ala54/Ala54 and Ala54/Thr54 genotypes. There was a positive correlation between FABP2 levels and BMI, SBP and DBP, and a negative correlation with HDL-C. CONCLUSIONS: The Thr54 allele of the FABP2 Ala54Thr polymorphism was associated with an increased incidence of peripheral atherosclerosis combined with T2DM in the population studied.

Association of chemerin Rs17173608 and vaspin Rs2236242 gene polymorphisms with metabolic syndrome in Egyptian women.

AIM: The metabolic syndrome is a complex of interrelated risk factors for cardiovascular disease and diabetes. The adipokines, chemerin and vaspin, are known to have metabolic regulatory roles. This study aimed to assess the relation of chemerin rs17173608 and vaspin rs2236242 polymorphisms with metabolic syndrome and its related phenotypes in Egyptian women. SUBJECTS AND METHODS: The study included 100 healthy female subjects and 100 metabolic syndrome patients. The component traits of metabolic syndrome were determined and the genotypes of the polymorphisms were assessed using the tetra amplification refractory mutation system polymerase chain reaction procedure. RESULTS: The minor G allele of the chemerin rs17173608 polymorphism had a significantly higher frequency in metabolic syndrome patients (p = 0.0001). The component traits of metabolic syndrome were significantly increased in the carriers of the GG and TG genotypes. In contrast, the rare A allele of vaspin rs2236242 polymorphism was significantly higher in the control subjects (p = 0.005). The carriers of the TA and AA genotypes showed significant relation with lower values of the phenotypes of metabolic syndrome. CONCLUSION: Metabolic syndrome in Egyptian females is associated with the minor allele of chemerin rs17173608 polymorphism, whereas the minor allele of vaspin rs2236242 polymorphism plays a protective role against metabolic syndrome.

Relation of myeloperoxidase-463G/A polymorphism with metabolic syndrome and its component traits in Egyptian women.

CONTEXT: Myeloperoxidase is a heme protein secreted by activated macrophages and generates intermediates that oxidize lipoproteins. Myeloperoxidase-463G/A is a functional polymorphism involved in regulation of myeloperoxidase expression. OBJECTIVE: The aim of this study is to assess the relation of myeloperoxidase-463G/A polymorphism with metabolic syndrome and its component traits in Egyptian women from the Suez Canal area. METHODS: The study includes 100 healthy female subjects and 100 metabolic syndrome patients. The component traits of metabolic syndrome are determined and the genotypes of the polymorphisms assessed using the PCR-RFLP technique. RESULTS: There was no significant difference in the allele frequencies between the metabolic syndrome and control groups. However, the GA and AA genotypes were associated with lower total cholesterol, LDL-C, systolic and diastolic blood pressure in the patients. CONCLUSION: Myeloperoxidase-463G/A polymorphism is not associated with the incidence of metabolic syndrome.

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.

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

AIM: 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. METHODS: The study population was divided into two groups: the study group included 66 RA patients diagnosed according to the American College of Rheumatology (ACR) classification criteria for RA, and the control group included 66 healthy adults who were age-and sex-matched to the RA group. All RA patients were assessed by Disease Activity Score (DAS28), ACR Classification of Global Functional Disability Status and Sharp's score as outcome measures. Gene investigations for ACE I/D polymorphism were performed by polymerase chain reaction (PCR) in both groups. RESULTS: The ACE I/D polymorphism was the (D/D) genotype in 60.6% (n = 40) of RA patients, the (I/D) genotype in 31.8% (n = 21) and the (I/I) genotype in 7.6% (n = 5). The frequency of (D) carriage was significantly higher in the RA cases than in the control group (76.5% vs. 53.8%, respectively, P = 0.0002). ACE D allele carriers were at higher risk of RA, 2.8 times higher than (I) carriers and those who had the homozygote (DD) genotype had 5.6 times the possibility of having RA. No correlations were observed between the homozygote (DD) genotype and disease activity or severity in RA patients. CONCLUSIONS: Our study suggests that high frequency of the ACE D allele contributes to the heritability of RA susceptibility compared to other ACE alleles. On the other hand, no association was detected between ACE I/D polymorphism and the severity of RA.

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.

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.

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 (HbA(1c)) 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 Ile(105)Val 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 HbA(1c)) 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 HbA(1c) in patients with diabetes mellitus.