CXCL9 and NT-proBNP, a notable link between inflammatory mediator and cardiovascular disease biomarker in rheumatoid arthritis.

INTRODUCTION: Cardiovascular disease (CVD) is the most critical extra-articular manifestation of rheumatoid arthritis, and inflammatory molecules contribute to its pathogenesis. Recently, CXCL9 has been considered an inflammatory chemokine associated with the pathogenesis of CVD. Here, we evaluated the association of plasma CXCL9 with well-established cardiac biomarkers, including HS-CRP (High sensitivity C-reactive protein) and NT-ProBNP (N-terminal pro-B-type natriuretic peptide), in newly diagnosed and under-treatment RA patients. METHODS: Thirty newly diagnosed patients, 30 under-treatment RA patients, and 30 healthy subjects were recruited. The plasma concentration of CXCL9 and NT-ProBNP was measured using the ELISA method. The HS-CRP levels was measured in plasma samples using latex-enhanced immunoturbidimetric test. RESULTS: We found increased plasma levels of CXCL9, HS-CRP, and NT-proBNP in RA patients compared to healthy subjects, besides that the concentration of CXCL9, HS-CRP, and NT-ProBNP showed elevated levels in newly diagnosed RA patients compared to under-treatment group. The mean plasma concentration of CXCL9, NT-proBNP, and HS-CRP were statistically different among healthy subjects, newly diagnosed, and under-treatment RA patients (p < 0.001, p = 0.016, and p < 0.001, respectively). We also found a significant positive correlation between CXCL9 and DAS-28 (p = 0.0005, r = 0.436) in the patients' group (new-case + under-treatment). There was a significantly positive correlation between CXCL9 and NT-proBNP in newly diagnosed and under-treatment patients (p = 0.020, r = 0.424; p < 0.0001, r = 0.853, respectively). In the patient's group (new-case + under-treatment), there was a significantly positive correlation between CXCL9 with NT-proBNP (p < 0.001, r = 0.703) and CXCL9 with HS-CRP (p = 0.015, r = 0.313). CONCLUSION: CXCL9 correlates significantly with well-established cardiovascular biomarkers, including HS-CRP and NT-ProBNP in RA patients. Key Points • CXCL9 is an inflammatory marker in RA. • CXCL9 has correlated with DAS-28. • There is a strong correlation between CXCL9 with NT-proBNP and HS-CRP.

Variants and Haplotypes of SIRT1 (rs7895833, rs7069102, and rs2273773) are Associated with the Risk of Preeclampsia and Affect the Trace Elements and Antioxidant Enzymes Levels.

Preeclampsia is the most common and serious complication of pregnancy. Variants of Sirtuin-1 (SIRT1) as a key player in the regulation of oxidant/antioxidant signaling pathways might be involved in the pathogenesis of preeclampsia. In the present case-control study 300 women with and without preeclampsia were studied for SIRT1 variants (rs7895833, rs7069102, and rs2273773) and haplotypes. Also, the relationship of glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities and Zn, Cu, and Se levels to the polymorphisms were investigated. The SIRT1 rs7895833 A > G, rs7069102 C > G, and the rs2273773 C > T polymorphisms were associated with the risk of preeclampsia. We found the haplotypes G (rs7895833) C (rs7069102) C (rs2273773), GCC, and ACC compared to the AGT decreased the risk of preeclampsia. The risk haplotype of AGT was associated with higher GPx activity compared to the GCC haplotype. A significantly higher level of Cu and lower levels of Zn and Se in patients with preeclampsia compared to controls were detected. Also, a significantly lower SOD and higher GPx activity in preeclamptic patients compared to controls were found. The three risk genotypes of AA (rs7895833), GG (rs7069102), and TT (rs2273773) significantly decreased the Zn level and SOD activity, and the TT genotype (rs2273773) increased the Cu level in all studied women. The presence of rs7069102 polymorphism was associated with enhanced systolic blood pressure. For the first time, we indicated three SIRT1 polymorphisms and the AGT haplotype are risk factors for preeclampsia development. Also, SIRT1 variants and haplotypes affect the levels of antioxidant enzymes and their cofactors, complicating the pregnancy outcome.

CXCL9 and its Receptor CXCR3, an Important Link Between Inflammation and Cardiovascular Risks in RA Patients.

Cardiovascular disease (CVD) is the most common cause of mortality in rheumatoid arthritis (RA), and Inflammation has a decisive role in its pathogenesis. CXCL9 contributes to multi aspects of inflammatory reactions associated with the pathogenesis of CVD. In the current study, we evaluated the association of plasma CXCL9 and CXCR3 gene expression with Cardiovascular risk factors in RA patients for the first time. Thirty newly diagnosed, 30 on-treatment RA patients, and 30 healthy subjects were recruited in this study. The plasma concentration of CXCL9 and CXCR3 gene expression were measured using ELISA and Real-Time PCR, respectively. The CVD risk was evaluated using Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE). The plasma levels of CXCL9 were significantly higher in the newly diagnosed and on-treatment RA patients compared to the control group (P < 0.0001 and P < 0.001, respectively). Also, The CXCR3 gene expression was strongly elevated in newly diagnosed and on-treatment patients (P < 0.001 and P < 0.01, respectively). The CXCL9 and CXCR3 were significantly associated with RA disease activity (P = 0.0005, r = 0.436; P = 0.0002, r = 0.463, respectively). The FRS was remarkably higher in newly diagnosed and on-treatment patients (P = 0.014 and P = 0.035, respectively). The CXCR3 gene expression significantly correlated with age, systolic blood pressure, FRS, and SCORE (P = 0.020, r = 0.298; P = 0.006, r = 0.346; P = 0.006, r = 0.349; P = 0.007, r = 0.341, respectively). The CXCL9 plasma concentration had a significant negative correlation with plasma HDL and LDL levels (P = 0.033, r = -0.275; P = 0.021, r = -0.296, respectively). CXCL9 and CXCR3 correlates with different variables of CVD in RA.

Association of angiotensin-converting enzyme (ACE) I/D variation with biochemical parameters and oxidative stress markers in systemic lupus erythematosus patients in west of Iran.

PURPOSE: We aimed to study insertion/deletion (I/D) variation (rs4646994) of ACE gene in a group of SLE patients in west of Iran and its possible relationship with oxidative stress. METHOD AND RESULTS: Genotypes and allele frequencies related to ACE (I/D) variation were determined in 108 SLE patients and 110 gender and age-matched healthy controls using PCR. Neopterin, malondialdehyde (MDA), and serum lipid concentrations were determined by HPLC and enzyme assay respectively. The overall distribution of ACE I/D genotypes in SLE patients was different from that of the control group (P = 0.005). DD genotype compared to ID genotype increased the risk of SLE (OR = 2.57, 95% CI 1.4-4.8, P = 0.003). ID genotype compared to the II genotype decreased the risk of disease (OR = 0.45, 95% CI 0.2-0.99, p = 0.042). SLE patients with DD, ID, and II genotypes had lower paraoxonase (PON) activity and higher serum levels of MDA and neopterin versus control patients. We also detected a significant protective effect against SLE in presence of ACE I alleles and lack of angiotensin II receptor, type 1 (AGTR1) A1166C (NCBI reference SNP id: rs5186), C alleles in this study (OR = 0.31, 95% CI 0.14-0.68, P = 0.002). CONCLUSIONS: Carriers of the DD genotype of ACE gene with higher serum concentrations of neopterin and MDA, and lower PON activity had a high risk to develop SLE, while ID genotype decreased the risk of disease development by 2.22 times compared to II genotype.

The Association between Apolipoprotein E Genotypes and Serum Malondialdehyde Level with End-Stage Renal Disease.

Background: The Apolipoprotein E (ApoE) polymorphism plays an important role in the pathophysiology of end-stage renal disease (ESRD). Additionally, ApoE may contribute to the progression of oxidative stress. Thus, this study aimed to determine the ApoE gene polymorphism and evaluate the malondialdehyde (MDA) level in ESRD patients and healthy individuals. Methods: The present cross-sectional study was conducted at 2010 at Kermanshah University of Medical Sciences (Kermanshah, Iran). The study population comprised ESRD patients (n=136) and healthy individuals (n=137). The MDA level was assessed using high-performance liquid chromatography (HPLC), and the frequencies of ApoE gene alleles were analyzed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). The data were analyzed using Statistical Package for Social Sciences (SPSS), version 13. The significant differences of ApoE genotypes in case and control groups were assessed using Pearson's Chi square tests, and two-tailed Student's tests. A logistic regression model was used to calculate the odd ratio. P<0.05 was considered statistically significant. Results: According to the results, ESRD patients had a higher frequency of the E2/E3 genotype than the healthy group (P<0.001). The results indicated that E3/E4 genotype frequency in the patients' group was higher than that of the control group (P=0.026). Furthermore, the E3/E2 (OR=5.7, 95% CI=2.68-12.14) (P<0.001) and E3/E4 (OR=1.57, 95% CI=1.05-2.34) (P=0.029) genotypes were found to increase the risk of ESRD. Moreover, the MDA level in ESRD patients was higher than the healthy individuals (P<0.001). The patients with E3/E2 (P<0.001) and E3/E4 (P<0.001) genotypes had a higher level of MDA than the control group. Conclusion: According to the findings, patients with ESRD had higher genotypes of E3/E2 and E3/E4, which suggests a higher risk of developing ESRD.

Brain targeting based nanocarriers loaded with resveratrol in Alzheimer's disease: A review.

Alzheimer's disease (AD) is one of the chief neurological difficulties in the aged population, identified through dementia, memory disturbance, and reduced cognitive abilities. ß-amyloid (Aß) plaques aggregations, generation of reactive oxygen species, and mitochondrial dysfunction are among the major signs of AD. Regarding the urgent need for the development of novel treatments for neurodegenerative diseases, researchers have recently perused the function of natural phytobioactive combinations, such as resveratrol (RES), in vivo and in vitro (animal models of AD). Investigations have shown the neuroprotective action of RES. This compound can be encapsulated by several methods (e.g. polymeric nanoparticles (NPs), solid lipid nanoparticles, Micelles, and liposomes). This antioxidant compound, however, barely crosses the blood-brain barrier (BBB), thereby limiting its bioavailability and stability at the target sites in the brain. Thanks to nanotechnology, the efficiency of AD therapy can be improved by encapsulating the drugs in a NP with a controlled size (1-100 nm). This article addressed the use of RES, as a Phytobioactive compound, to decrease the oxidative stress. Encapsulation of this compound in the form of nanocarriers to treat neurological diseases to improve BBB crossing is also discussed.

Interleukin-1α and tumor necrosis factor α as an inducer for reactive-oxygen-species-mediated NOD-like receptor protein 1/NOD-like receptor protein 3 inflammasome activation in mononuclear blood cells from individuals with chronic insomnia disorder.

BACKGROUND AND PURPOSE: There is some evidence that cytokines may play an important role in sleep deprivation; however, the underlying mechanisms are still unknown. So, the present study aimed to evaluate the relationship between NOD-like receptor protein 1 (NLRP1) and NOD-like receptor protein 3 (NLRP3) inflammasome activation of blood cells and serum levels of cytokines in individuals with chronic insomnia disorder (CID). METHODS: Blood samples were collected from 24 individuals with CID and 24 healthy volunteers. The inflammasome activation was evaluated using real-time polymerase chain reaction of NLRP1, NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and caspase-1; western blot of NLRP1 and NLRP3; caspase-1 activity assay; and serum levels of interleukin-1ß (IL-1ß), IL-18 and other cytokines using enzyme-linked immunosorbent assay. Reactive oxygen species generation in blood cells were detected by flow cytometry assay. Also, magnetic resonance imaging scans were obtained on a Siemens Magnetom Avanto 1.5 T MRI whole-body scanner using an eight-channel head coil. RESULTS: Increased activity of NLRP1 and NLRP3 inflammasomes in blood cells, increased serum levels of pro-inflammatory cytokines and decreased serum levels of IL-10 and transforming growth factor ß in individuals with CID were found. Significant correlation was observed between increased serum concentration of IL-1ß and the severity of insomnia in individuals with CID. The levels of reactive oxygen species in blood cells were found to be correlated with IL-1α and tumor necrosis factor α concentrations in sera from individuals with CID. Moreover, the individuals with CID demonstrated increased right cerebellum cortex and lateral ventricle mean diffusivity bilaterally compared to controls. CONCLUSIONS: This study provided new insights on the pathogenesis of CID and the effects of cytokines on inflammasome activation.

IgLON5 autoimmunity tested positive in patients with isolated chronic insomnia disease.

In the patients with neurological autoimmune diseases such as anti-IgLON5 disease, insomnia symptoms are very common. Clinical diagnosis of the anti-IgLON5 disease is usually made when neurodegenerative processes have occurred. To find the early signs of anti-IgLON5 disease, we evaluate the presence of IgLON5 autoantibodies in the serum of patients with chronic insomnia disease. Based on video-polysomnography, 22 individuals with isolated chronic insomnia disease were found. A control group of 22 healthy people was chosen using the Pittsburgh Sleep Quality Index (PSQI). An indirect immunofluorescence cell-based test of serum anti-IgLON5 antibodies was used to investigate IgLON5 autoimmunity. Anti-IgLON5 antibodies were detected in the serum of four of these patients with the titer of 1/10. The presence of IgLON5 autoantibodies in some patients with chronic insomnia disease can be considered a causing factor of insomnia which can be effective in more specific treatments of these patients. Moreover, the recognition of anti-IgLON5 disease in the early stages and before the progression of tauopathies can be useful in effective and timely treatment.

Association of Matrix Metalloproteinase-2 (MMP-2) and MMP-9 Promoter Polymorphisms, Their Serum Levels, and Activities with Coronary Artery Calcification (CAC) in an Iranian Population.

The serum levels and activity of matrix metalloproteinases (MMPs) are associated with the risk of coronary artery calcification (CAC). We sought to investigate the association between MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs with MMP-2 and MMP-9 serum levels and activity in individuals with CAC. One hundred and fifty-five cases with CAC and 155 healthy individuals as control group from West of Iran were included and frequency of genotypes and alleles of rs243866 and rs3918242 in MMP-2 and MMP-9 genes were determined using PCR-RFLP. We also investigated the serum levels of MMP-2 and MMP-9 and their activity using ELISA and gelatin zymography, respectively. Additionally, serum biochemical parameters including FBS (fasting blood sugar), urea, creatinine, cholesterol, triglyceride, HDL (high-density lipoprotein), LDL (low-density lipoprotein), calcium, and phosphorus as well as blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)) were measured. Our results showed that both serum levels of MMP-2 and MMP-9 (P < 0.001) and their activity (P < 0.001) were higher in individuals with CAC when compared to the control group. Carrying A and T alleles in MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs, respectively, may predispose the individuals to CAC by acting as the risk factors. Serum levels and activity of MMP-2 and MMP-9 were found to be higher in CAC cases when compared to the healthy controls. Carriers of A allele in rs243866 SNP and T allele in rs3918242 SNP were shown to have higher MMP-2 and MMP-9 serum levels and activity that may result in increased ECM degradation and support the initiation and development of calcification.

Increased plasma levels of CCL20 in peripheral blood of rheumatoid arthritis patients and its association with clinical and laboratory parameters.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily affects small joints. The impaired chemokine and cytokine responses are essential pathological mechanisms for the RA clinical presentation. Given the role of chemokines and inflammatory reactions in RA pathogenesis, we evaluate the association between the plasma concentration of CCL20 with the clinical and laboratory parameters in newly diagnosed RA patients. MATERIAL AND METHODS: Forty-five newly diagnosed RA patients and forty-five healthy subjects were enrolled in this study. The plasma levels of CCL20, rheumatoid factor, and anti-citrullinated peptide antibodies were measured using the enzyme-linked immunosorbent assay (ELISA) technique. RESULT: The plasma levels of CCL20 were increased significantly in RA patients compared to the healthy controls (p < 0.0001). There was a positive correlation between CCL20 and RF, anti-CCP, ESR, and DAS-28 (p < 0.0001, r = 0.669; p < 0.015, r = 0.358; p < 0.0001, r = 0.586; p < 0.0001, r = 0.769). CONCLUSION: The increased plasma levels of CCL20 in newly diagnosed RA patients may contribute to RA pathogenesis, and it is in association with clinical and laboratory parameters. Key Points • CCL20 has a contribution to the early phase of RA.

The role of caveolin-1 and endothelial nitric oxide synthase polymorphisms in susceptibility to prostate cancer.

Caveolin-1(cav-1) is overexpressed in prostate cancer (PC) and is associated with progression of the disease. We investigated the effects of CAV1-T29107A and endothelial nitric oxide synthase (eNOS) G894T polymorphisms on the serum levels of testosterone, NO and prostate-specific antigen (PSA) in patients with PC. We genotyped cav-1 and eNOS genes in 112 PC patients and 150 healthy controls by PCR-RFLP. Serum levels of NO2- and NO3- were measured using spectrophotometry, and serum levels of testosterone and PSA were measured by ELISA. The frequencies of CAV1 genotypes A/T vs. A/A according to the dominant model AT + TT vs. AA genotype and T allele were significantly higher in PC patients in comparison with the control group and considerably increased the risk of disease by 2.19-, 1.44- and 1.6-fold, respectively. AT + TT genotypes were associated significantly with the increased risk of PC in those with smoking or diabetes by 3.08-fold (P = .004). Individuals carrying concurrently the T allele of CAV1 A29107T and the T allele of eNOS G894T genes had a significantly increased risk of PC by 2.52-fold (P = .009). We did not find any significant relationship between eNOS G894T genotypes and alleles with susceptibility to PC. Our results highlighted the significance of CAV1-T29107A SNP but not (eNOS) G894T in the susceptibility to PC in our the population that we have studied.

Evaluation of The Relationship among The Levels of SIRT1 and SIRT3 with Oxidative Stress and DNA Fragmentation in Asthenoteratozoospermic Men.

BACKGROUND: Reactive oxygen species (ROS) play a crucial role in etiology of DNA fragmentation and lipid peroxidation in sperm, leading to infertility in men. The silent information regulators SIRT1 and SIRT3 are members of the sirtuins protein family known to be involved in cancer genetics, aging and oxidative stress responses. The aim ofthis study is to determine the correlation between SIRT1 and SIRT3 with antioxidants, oxidative stress biomarkers, and DNA fragmentation in the semen of asthenoteratozoospermic and normozoospermic men. MATERIALS AND METHODS: In this case-control study, after spermogram analysis the specimens were divided into two groups, normozospermic (n=40) and asthenoteratozoospermic (n=40), according to World Health Organization (WHO) standards. Sperm DNA fragmentation was evaluatedusing the sperm chromatin dispersion (SCD) test.Catalase activity was measured using the Aebi spectrophotometeric method. Total antioxidant capacity (TAC) level and superoxide dismutase (SOD) activitywere measured by using commercially available colorimetric assays. Enzyme-linked immune sorbent assay (ELISA) was used to measure SIRT1 and SIRT3 protein levels of seminal plasma. Malondialdehyde (MDA) level in seminal plasma was determined by high-performance liquid chromatography (HPLC). RESULTS: The asthenoteratozoospermic group had significantly lower catalase and SOD activities and TAC levels in comparison with the normozoospermic group (P<0.001).The percentage of DNA fragmentation and MDA level in the asthenoteratozoospermic group were remarkably higher than in the normozoospermic group. The SIRT1 and SIRT3 protein levels in seminal plasmawere remarkably lower in asthenoteratozoospermic group than the normozoospermic group (P<0.001). CONCLUSION: The results of this study suggest that SIRT1 and SIRT3 protein levels are negatively correlated with oxidative stress and DNA fragmentation in semen. The low levels of SIRT1 and SIRT3 in asthenoteratozoospermic men may lead to an increase in oxidative stress, DNA fragmentation, and lipid peroxidation that eventually result in immotile and immature spermatozoa (asthenoteratozoospermia).

Activities and polymorphisms of MMP-2 and MMP-9, smoking, diabetes and risk of prostate cancer.

Matrix metalloproteinases (MMPs) are a group of zinc dependent enzymes that are involved in tumor cell invasion and metastasis. The role of MMP-2 and -9 genetic polymorphism in different malignancies has been the subject of numerous studies. The present research has attempted to discover any positive correlation between MMP-2 and MMP-9 SNPs and prostate cancer (PCa) in patients with a history of either diabetes or smoking habits. 112 PCa-patients and 150 unrelated healthy-controls that matched for age and sex were selected for present case-control study. MMP-2 -1575G/A and MMP-9 -1562 C/T polymorphisms detected by PCR-RFLP, serum tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), testosterone, prostate-specific antigen (PSA), free-prostate-specific-antigen (fPSA), and fPSA/PSA levels were detected by ELISA and enzyme assay, respectively. MMP-2 and MMP-9 activities were measured by gelatin-zymography. Covariates were considered as age, status of cigarette smoking, and a possible history of diabetes mellitus (DM). The frequency of -1575 MMP-2 A/A + A/G and -1562 MMP-9 C/T + T/T genotypes were higher in PCa-patients with DM (74.3%,p = 0.003) and with smoking habits (72.5%,p = 0.005). These genotypes were associated with the increased risk of prostate cancer in smokers (3.52-folds) and in individuals with history of DM (4.34-folds). A significant positive association was found between level of TIMPs (TIMP -1 and TIMP-2) and BMI in PCa-patients and also between testosterone levels and MMP-9 activity in healthy control subjects. For the first time, this study demonstrated that activities of MMP-2 -1575G/A and MMP-9 -1562C/T variants in association with smoking and diabetes are considered significant risk factors for PCa.

Assessment of GSTO1 (A140D) and GSTO2 (N142D) Gene Polymorphisms in Iranian Women with Polycystic Ovarian Syndrome.

BACKGROUND: Glutathione S-transferases (GSTs) protect cells from oxidative stress (OS). In humans, the GST omega class contains two expressed genes, GSTO1 and GSTO2. Because OS is involved in the pathogenesis of polycystic ovary syndrome (PCOS), the aim of this study was to investigate the relationship between GSTO1 A140D (rs4925) and GSTO2 N142D (rs156697) polymorphisms in PCOS patients. METHODS: 175 PCOS patients and 161 healthy controls were selected among women in Kermanshah province, Iran. GSTO1 and GSTO2 were genotyped using allele-specific PCR (AS-PCR) and PCR-RFLP, respectively. RESULTS: For GSTO1, the DD genotype and the D allele led to 2.17- (P= 0.02) and 1.5-fold (P= 0.01) increases, respectively, in the odds ratios for PCOS. No significant difference was found between control and patient groups for the GSTO2 N142D genotype or allele frequency. GSTO1 and GSTO2 genotype interaction analysis showed that individuals with the GSTO1 AD or DD genotypes and the GSTO2 NN or DN genotypes had a 1.53-fold (P= 0.007) increase in PCOS risk over GSTO1 AA and GSTO2 DD individuals. CONCLUSION: The GSTO1 A140D polymorphism is a risk factor for PCOS.

Association of AHSG gene polymorphisms with serum Fetuin-A levels in individuals with cardiovascular calcification in west of Iran.

Fetuin-A (AHSG) is a multifunctional secretory protein and acts as an ectopic valve and artery calcification inhibitor. We assessed the correlation between serum levels of Fetuin-A and both exon 6 (248 C/T) and exon 7 (256 C/G) mutations in patients with coronary artery calcification (CAC), mitral annular calcification (MAC), and aortic valve calcification (AVC). 184 patients and 184 healthy individuals as control group were included. The genetic variants of rs4917 and rs4918 for the AHSG gene were determined by PCR-RFLP and T-ARMS PCR techniques. Fetuin-A levels, fasting blood sugar (FBS), urea, creatinine, calcium phosphorus, and lipid profile were measured. Fetuin-A levels were remarkedly lower in individuals with AVC, MAC, and CAC comparing to the control group (p < 0.001). The CT + TT genotypes and the T allele (AHSG Thr248Met) were associated with the risk of calcification of heart valves and coronary artery by 1.31 and 1.27 times in the patient group, respectively. The frequency of CT genotype and T allele was considerably higher in the patient group comparing to the control group. Patients with T allele (CT + TT) had higher levels of FBS, urea, low-density lipoproteins (LDL)-C, phosphorus, systolic blood pressure (SBP), diastolic blood pressure (DBP) while decreased levels of triglyceride, high-density lipoproteins (HDL)-C, calcium and fetuin-A in comparison to control group. Additionally, there was a positive correlation between serum FBS, urea, creatinine, HDL-C, calcium with fetuin-A, and a negative correlation between phosphorous level, SBP, and DBP with fetuin-A. T allele in rs4917 Single nucleotide polymorphism (SNP) is the risk allele of calcification of heart valves and coronary arteries and fetuin-A levels correlates negatively with the occurrence of the disease.

The Insulin-like Growth Factor-1 (G>A) and 5,10-methylenetetrahydrofolate Reductase (C677T) Gene Variants and the Serum Levels of Insulin-like Growth Factor-1, Insulin, and Homeostasis Model Assessment in Patients with Acne Vulgaris.

BACKGROUND & OBJECTIVE: To find an association between gene variants of insulin-like growth factor-1 (IGF-1) and 5,10-methylenetetrahydrofolate reductase (MTHFR) with the risk of acne vulgaris (AV). METHODS: In a case-control study, we investigated 150 AV patients and 148 healthy individuals (aged 18-25 years) for the IGF-1 G>A and MTHFR C677T polymorphisms, as well as the serum levels of IGF-1, insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR). The serum biochemical parameters and the genotypes of IGF-1 G>A and MTHFR C677T were detected by using appropriate kits and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods, respectively. RESULTS: The frequencies of IGF-1 and the MTHFR polymorphisms were not significantly different comparing patients and controls. The serum level of IGF-1 was 179.8±72.8 µg/L in AV patients compared to 164.6±63.7 µg/L in controls (P=0.056). The serum level of insulin in female patients was significantly higher than controls. The HOMA was 3.54±5.6 in patients compared to 1.16±1.4 (P<0.001) in controls. Significantly higher levels of fasting blood sugar (FBS), total cholesterol, and low-density lipoprotein-cholesterol (LDL-C) were detected in female patients than controls. However, the level of estradiol was significantly lower in female patients than in controls. In females, the presence of the MTHFR T allele was associated with significantly higher levels of FBS and LDL-C, as well as a significantly lower level of estradiol compared to those carriers of the C allele. CONCLUSION: We found the absence of an association between IGF-1 and MTHFR polymorphisms with the risk of AV. However, increased insulin, IGF-1, and HOMA levels in AV patients indicated the effect of insulin and insulin resistance in the risk of AV and its severity.

The impaired gene expression of adenosine monophosphate-activated kinase (AMPK), a key metabolic enzyme in leukocytes of newly diagnosed rheumatoid arthritis patients.

The disturbed immune homeostasis is involved in the pathogenesis of an array of autoimmune diseases like rheumatoid arthritis (RA). The adenosine monophosphate-activated protein kinase (AMPK) with a pivotal role in immunometabolism process, also plays a regulatory function in the immune system. This study aims to evaluate the alteration of AMPK gene expression in peripheral blood leukocytes of RA patients and its effects on disease severity as well as plasma levels of anti-inflammatory cytokines. 60 RA patients, including 30 newly diagnosed and 30 patients whose disease were under controlled with the combinational disease-modifying anti-rheumatic drug (DMARD), as well as 30 healthy subjects, were enrolled in our study. The gene expression of AMPK was evaluated using real-time PCR method. The plasma concentrations of IL-10 and TGF-ß1 were measured using sandwich ELISA. The gene expression of AMPK was significantly lower in the newly diagnosed RA patients in comparison with the control group (P = 0.049). Inversely, in RA patients who received DMARD therapy, the gene expression of AMPK was significantly higher than the control group (P = 0.003). There was no significant correlation between AMPK gene expression and plasma levels of IL-10 and TGF-ß1. The plasma levels of TGF-ß1 was significantly higher in both newly diagnosed and under-treatment patients compared with healthy subjects (P < 0.001). The impaired gene expression of AMPK in peripheral blood leukocytes and elevated levels of plasma TGF-ß1 can be contributed in RA pathogenesis.

Vitamin D-binding protein and vitamin D receptor genotypes and 25-hydroxyvitamin D levels are associated with development of aortic and mitral valve calcification and coronary artery diseases.

To assess the association between vitamin D-Binding Protein (VDBP rs7041T>G) and vitamin D receptor (VDR rs1544410G>A) gene polymorphisms with susceptibility to cardiovascular diseases in population from west of Iran. Two hundred forty-nine individuals with cardiovascular disease (92 with aortic and Mitral Valves Calcification (AMVC) and 157 with Coronary Artery Diseases (CAD) that their diseases were confirmed by echocardiography and angiography and unrelated 182 healthy controls (gender and age-matched) were selected for this case-control study. The VDR 1544410G>A, and VDBP 7041T>G genotyping were detected by PCR-RFLP, serum vitamin D and lipid concentrations were measured by ELISA and enzyme assay, respectively. The VDR rs1544410G>A gene is a strong risk factor for CAD (OR = 1.28, p = 0.002) and the dominant genotype (T/G+G/G) of VDBP 7041 T>G SNP plays a protective role (OR = 0.67, p = 0.003) in AMVC development in studied population. In addition, lower level of vitamin D strongly increased the risk of CAD (15 ± 11.02 vs. 21.3 ± 18 µg/L, p = 0.043) and AMVC (12.1 ± 13.1 vs.21.3 ± 18 µg/L, p = 0.014) development in individuals carrying T/T genotype of VDBP 7041 T>G gene polymorphism. There was a strong interaction between A allele VDR rs1544410 and G allele of VDBP rs7041 genes in a protective role (OR = 0.74, p = 0.044) in AMVC patients). CAD and AMVC patients were deficient in vitamin D, i.e. their level of vitamin D was strongly lower than that in the control group. Our findings for the first time indicated that there is a strong association between vitamin D deficiency, lipid profile and the VDR rs1544410G>A and rs7T41>G VDBP genes polymorphisms. These interactions may be one of the important factors for CAD and AMVC incidence.

Association between CYP19A

Acne vulgaris (AV) is a common skin disease that causes physical and psychological problems for the affected individual. In addition to systemic changes in hormone levels, overproduction of local steroids, especially androgens are associated with AV. Cytochrome (CYP) 19 is involved in the synthesis of estrogens. The aim of the present study was to investigate the influence of CYP19A

Association between the -11377 C/G and -11391 G/A polymorphisms of adiponectin gene and adiponectin levels with susceptibility to type 1 and type 2 diabetes mellitus in population from the west of Iran, correlation with lipid profile.

Adipose tissue, an endocrine organ, secretes bioactive factors including adiponectin. Adiponectin is a protein hormone that enhances insulin sensitivity through increased fatty acid oxidation and inhibition of hepatic glucose production. We assessed the association of the adiponectin promoter region polymorphisms -11391 G/A and -11377 C/G with susceptibility to type 1 (T1DM) and type 2 (T2DM) diabetes mellitus in the population of west Iran. Also, we investigated the effect of adiponectin level and lipid profile on T1DM and T2DM development. In this case-control study, we recruited 189 patients with diabetes (100 T2DM and 89 T1DM) and 161 sex and age-matched unrelated healthy controls. Adiponectin mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the protein level was measured by the enzyme-linked immunosorbent assay. Other biochemical parameters were determined by routine laboratory methods. The G allele of adiponectin gene at -11377 position (C/G) significantly increased the risk of T1DM. With respect to genotype models, codominant (2.97 times), dominant (3.6-fold), and over-codominant (2.9-fold) patients with T1DM who carried -11377 C > G single-nucleotide polymorphisms were significantly susceptible to the development of the disease. A significantly higher level of adiponectin in T1DM was oberved compared with the control group. In contrast, patients with T2DM had lower adiponectin levels compared with healthy controls. The genotype distributions of -11391 G/A polymorphisms were the same for patients with diabetes and control groups. The presence of G allele at -11377 C/G adiponectin gene significantly increased serum adiponectin level and may be a risk factor for T1DM susceptibility among the western Iranian population.