Vascular Endothelial Growth Factor Genetic Variant Is Associated with in-Stent Restenosis after Percutaneous Coronary Intervention.

Background: In-stent restenosis (ISR) is an inevitable complication of percutaneous coronary intervention, with genetic factors thought to play a role in its pathogenesis. The vascular endothelial growth factor (VEGF) gene can have an inhibitory effect on ISR development. Accordingly, in the present study, we investigated the role of -2549 VEGF (insertion/deletion [I/D]) variants in ISR formation. Methods: Patients with ISR (ISR+) (n=53) and patients without ISR (ISR-) (n=67) were enrolled in this case-control study based on follow-up angiography 1 year after percutaneous coronary intervention between 2019 and 2020. The clinical characteristics of the patients were evaluated, and the frequencies of the alleles and genotypes of -2549 VEGF (I/D) variants were determined using polymerase chain reaction. The χ2 test was performed for the calculation of genotypes and alleles. A P value of less than 0.05 was considered the level of significance. Results: This study recruited 120 individuals at a mean age of 61.43±8.91 years in the ISR+ group and 62.09±7.94 years in the ISR- group. Women and men, respectively, comprised 26.4% and 73.6% of the ISR+ group and 43.3% and 56.7% of the ISR- group. A significant association was observed between the VEGF -2549 genotype frequency and ISR. The frequency of the insertion/insertion (I/I) allele was significantly higher in the ISR+ group than in the ISR- group, while the frequency of the D/D allele was higher in the latter group. Conclusion: Regarding ISR development, the I/I allele may be a risk allele and the D/D allele a protective allele.

Association of vitamin D receptor gene polymorphism with the occurrence of low bone density, osteopenia, and osteoporosis in patients with type 2 diabetes.

PURPOSE: This study aims to analyze the association between VDR gene polymorphism and the occurrence of "low bone density (LBD)/osteopenia/osteoporosis" or LBDOO in type 2 diabetes (T2D) patients among a clustered population in northwest of Iran. The studied VDR gene polymorphism included ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), EcoRV (rs4516035) and, TaqI (rs731236). METHODS: In this population-based cross-sectional study, patients with T2D were identified within a group of 1266 participants based on self-report of diabetes, history of diabetes medication, and recorded laboratory data. Separately for each polymorphism and gender, crude and adjusted (age, BMI) odds ratios (ORs) were calculated for participants with T2D through logistic regression analysis. RESULTS: The prevalence of T2D was 16.41% in people residing in the city of Sanandaj in 2011. Of the participants with T2D, 13.92% and 81.29% had osteoporosis and vitamin D deficiency, respectively. In women, the tt genotype of the TaqI gene significantly decreased the risk of LBDOO versus the Tt genotype, after adjusting for BMI and age (adjusted OR:0.18, CI95%: 0.03-0.97). Conversely, the EE genotype of the EcoRV gene enhanced the risk of LBDOO versus the Ee genotype (adjusted OR:7.64, CI95%: 2.03-28.72). CONCLUSION: The polymorphism of both TaqI and EcoRV genes was associated with the risk of LBDOO in women with T2D. This is the first time a study has highlighted this effect for the polymorphism of the EcoRV gene; we believe that this study would serve as a basis for future studies.

Association of Pro-inflammatory Cytokine Gene Polymorphism with Meniere's Disease in an Iranian Sample.

Meniere's disease (MD) is known as a rare chronic disorder of the inner ear with elevated serum levels of pro-inflammatory cytokines like tumor necrosis factor (TNF)-α, Interleukin (IL)-1, and IL-6. This study aims to evaluate genes polymorphism in some pro-inflammatory cytokines in a group of Iranian MD patients compared to the healthy controls. In this case-control study, 25 MD patients and 139 healthy controls were enrolled. DNA was extracted from blood samples, and single nucleotide polymorphisms were detected using polymerase chain reaction with sequence-specific primers assay. MD patients and controls were examined in terms of allele, genotype, and haplotype frequency of pro-inflammatory cytokine genes. Only the frequencies of alleles A/G at position -238 in the promoter of the TNF-α gene differed significantly between MD patients and healthy controls. G to A allele ratio was 23 and 3.6 in MD and controls, respectively. In individuals with MD, genotype GG was found to be significantly more prevalent at position -238 of the TNF-α gene promoter sequence. In addition, the heterozygote AG variant of -238 A/G TNF-α gene polymorphism was lower in MD patients than controls. Compared to the control group, the haplotype TNF- (-308, -238) AG was higher in MD patients, although not statistically significant. This is the first study that we know of that evaluates the frequencies of pro-inflammatory cytokine genes in an Iranian MD sample. This study shows the association between TNF-α and susceptibility to MD.

Meglitinide (repaglinide) therapy in permanent neonatal diabetes mellitus: two case reports.

BACKGROUND: Permanent neonatal diabetes mellitus (PNDM) presents with dehydration and hyperglycemia, which usually occurs during the first 12 months of life. Activating mutations of beta-cell adenosine triphosphate-sensitive potassium [KATP] channel subunits that cause opening of the channel are associated with PNDM. Some patients with PNDM respond to administration of a sulfonylurea derivative, which has long action on blood glucose even during hypoglycemia and has an apoptotic effect on beta cells. However, there have been no reports regarding treatment with meglitinide (repaglinide), which has rapid and short duration of action during the rise in blood glucose after meals that is more similar to beta cell function. It has no effects during hypoglycemia, so it does not cause neurological damage, and has no apoptotic effect on beta cells. We report herein the effects of repaglinide administration in the management and clinical outcome of two patients with PNDM during 9 and 10 years of follow-up. CASE PRESENTATION: Two Iranian infants were brought to our institution with poor general condition, dehydration, lethargy, and poor feeding. They had diabetic ketoacidosis at 52 days and 3.5 months of age, respectively. Their genetic analysis revealed mutations in the KCNJ11 gene encoding KIR6.2, so they both had PNDM. After treatment of diabetic ketoacidosis with insulin, they responded to sulfonylurea (glibenclamide) treatment, but were switched to repaglinide because of blood sugar fluctuations in terms of hyper- and hypoglycemia. Repaglinide was administered with the dosage of 0.04 mg/kg/day divided before every meal. RESULTS: The patients were 10 and 9 years old at the last visit, with normal growth parameters. The values of self-monitored blood glucose were well-controlled, and the hemoglobin A1C (HbA1C) levels ranged from 3.6 to 6.4% during the follow-up period. There was no complication of diabetes, neurological disorder, or adverse effects related to repaglinide. CONCLUSION: In every neonate or infant < 6 months of age with diabetes mellitus, PNDM should be considered. A trial of oral repaglinide can be performed and substituted for glibenclamide for prevention of hypoglycemia, neurological damage, and apoptosis of beta cells during long-term administration.

Hydro alcoholic green tea extract effect on high fat diet treated NMRI mice and 3T3L1 cells.

PURPOSE: In order to counteract the obesity has epidemics, since current anti-obesity drugs effects remain limited, there is a need to provide new options. As a project aiming to assess potential anti obesity natural compounds, the effects of consumption of a minimal dose of green tea hydro alcoholic extract (GT) on adipocyte differentiation of 3T3L1 cell line were investigated. METHODS: Obesity was induced in female NMRI mice (which are less used overall) by the use of a high fat diet. Mice were divided into four groups of control (C), treated control (TC), obese (O) and treated obese (TO). TC and TO groups received 8 mg/Kg/day of GT for 8 weeks, and weighted weekly, after what biochemical and histological parameters were measured. GT was used at doses of 100,150 and 200 µg/ml on 3T3L1, and staining with Oil-red-O was done for estimation of fat droplet accumulation. RESULTS: Body weight was found to be affected significantly by GT. Blood glucose levels did not show significant changes between groups, while triglycerides levels of the O group was significantly higher than the C group, but the TO group showed no significant difference with the C group upon GT treatment. Liver and visceral fat tissues showed more normalized tissue and less fat accumulation in the TO group. TO and TC groups showed an ameliorated morphologic state of liver tissues. GT was also able to decrease fat droplet formation in a dose-dependent manner. CONCLUSIONS: Adding a minimal amount of GT to the daily consumption may have preventive effects on fat accumulation in healthy subjects, while in obese cases, GT shows significant therapeutic effect.

Association of MTHFR C677T polymorphism with elevated homocysteine level and disease development in vitiligo.

Increasing evidence on the association of MTHFR gene polymorphism and serum homocysteine levels with autoimmune diseases such as vitiligo has made the MTHFR gene a very interesting candidate to be evaluated in different ethnicities and populations. We aimed to evaluate the levels of serum homocysteine and vitamin B12 and their associations with MTHFR C677T polymorphism in the Iranian population. This case-control study included 104 patients with vitiligo and 100 age- and sex-matched healthy control subjects. Serum vitamin B12 and homocysteine levels were measured by a chemiluminescence assay. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used for genotyping the polymorphism. The mean serum homocysteine levels were significantly higher in cases than controls and associated with disease activity (p < .001). Furthermore, the homozygous MTHFR C677T variant genotype was associated with vitiligo development (adjusted OR: 3.52, 95% CI: 1.09-11.32, p = .02) and elevated homocysteine level (p < .001). There was no association between serum vitamin B12 levels and the MTHFR C677T genotype. The homozygous variant MTHFR C677T may be considered as a risk factor for both elevated homocysteine levels and the development of vitiligo in the Iranian population. Although these results are not conclusive, they could elucidate the contribution of genetic and immune-mediated inflammatory factors to the pathogenesis of vitiligo.

The Role of ERRFI1+808T/G Polymorphism in Diabetic Nephropathy.

Nephropathy is a common diabetes complication. ERRFI1 gene which participates in various cellular pathways has been proposed as a candidate gene in diabetic nephropathy. This study aimed to investigate the role of +808T/G polymorphism (rs377349) in ERRFI1 gene in diabetic nephropathy. In this case-control study, patients including diabetes with nephropathy (DN=104), type 2 diabetes without nephropathy (DM=100), and healthy controls (HC=106) were included. DNA was extracted from blood, and genotyping of the +808T/G polymorphism was carried out using PCR-RFLP technique. The differences for genotype and allele frequencies for +808T/G polymorphism in ERRFI1 gene between DN vs. HC and DN+DM vs. HC were significant (P<0.05) while no significant difference between DN and DM was observed. The allele frequencies were significantly different in DN vs. HC and DN+DM vs. HC in males but not in females. G allele of +808T/G polymorphism in ERRFI1 gene has no significant role in development and progression of diabetic nephropathy in diabetes patients while it is a risk allele for developing diabetes in Iranian population.

The Association Analysis of Vascular Endothelial Growth Factor -2549 Insertion/ Deletion Variant and Endometriosis Risk.

Endometriosis is a debilitating disorder, defined as the presence of endometrial gland and stroma outside of the uterus. It may affect angiogenesis and vascular endothelial growth factor (VEGF) is one of the angiogenic factors that plays an important role in both physiological and pathological angiogenesis. The present study aimed to evaluate the association of VEGF -2549 insertion/deletion (I/D) polymorphism with endometriosis. This case-control study enrolled 244 (100 cases and 144 controls) women who were admitted for laparoscopy or laparotomy for gynecological procedures. Genomic DNA was separated from peripheral blood leukocytes and polymerase chain reaction (PCR) amplification was performed for genotyping of the VEGF gene Insertion/Deletion (I/D) polymorphism. The frequency of the II, ID, and DD genotype was 14%, 52% and 34% in patients versus 18.8%, 47.8% and 34% in controls. The results did not provide any evidence supporting the endometriosis risk related to the VEGF polymorphism in a group of Iranian women population.

HLA-Cw Allele Frequency in Definite Meniere's Disease Compared to Probable Meniere's Disease and Healthy Controls in an Iranian Sample.

INTRODUCTION: Several lines of evidence support the contribution of autoimmune mechanisms in the pathogenesis of Meniere's disease. The aim of this study was determining the association between HLA-Cw Alleles in patients with definite Meniere's disease and patients with probable Meniere's disease and a control group. MATERIALS AND METHODS: HLA-Cw genotyping was performed in 23 patients with definite Meniere's disease, 24 with probable Meniere's disease, and 91 healthy normal subjects, using sequence specific primers polymerase chain reaction technique. The statistical analysis was performed using stata 8 software. RESULTS: There was a significant association between HLA-Cw*04 and HLA-Cw*16 in both definite and probable Meniere's disease compared to normal healthy controls. We observed a significant difference in HLA-Cw*12 frequencies between patients with definite Meniere's disease compared to patients with probable Meniere's disease (P=0.04). The frequency of HLA-Cw*18 is significantly higher in healthy controls (P=0.002). CONCLUSION: Our findings support the rule of HLA-Cw Alleles in both definite and probable Meniere's disease. In addition, differences in HLA-Cw*12 frequency in definite and probable Meniere's disease in our study's population might indicate distinct immune and inflammatory mechanisms involved in each condition.

Interleukin-1 beta, interferon-gamma, and tumor necrosis factor-alpha gene expression in peripheral blood mononuclear cells of patients with coronary artery disease.

BACKGROUND: Several inflammatory mediators have been proposed to contribute to the pathogenesis of atherosclerosis. The aim of this study was to evaluate the quantitative expression of pro-inflammatory cytokines in un-stimulated peripheral blood mononuclear cell of patients with coronary artery disease (CAD). METHODS: Interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha, and interferon-gamma (IFN-γ) gene expression were evaluated in angiography confirmed patients with and without CAD in a case-control study using quantitative real-time polymerase chain reaction. RESULTS: A significant increase (P = 0.030) in IL-1ß gene expression was found in patients with CAD [median interquartile range (IQR) = 4.890 (6.084)] compared to patients without CAD [median (IQR) = 1.792 (3.172)]. Despite the increase in IFN-γ gene expression in patients with CAD [median (IQR) = 1.298 (3.896)] versus patients without CAD [median (IQR) = 0.841 (2.79)], there was not statistically significant difference (P = 0.990). CONCLUSION: Our results provide evidence for possible association between IL-1ß and development of atherosclerosis as a crucial cytokine that induce a network of signaling pathways. This finding if proved in future would suggest IL-1ß as a potent therapeutic target in CAD.