High-level expression of early growth response-1 and association of polymorphism with total IgE and atopy in allergic rhinitis adults

BackgroundEarly growth response-1 (Egr-1) is expressed in human airways and its polymorphisms have been associated with total IgE and atopy in asthmatic patients. We investigated the effects of Chinese-tagging single nucleotide polymorphism (SNP) of Egr-1 and its mRNA expression on allergic rhinitis (AR) traits.MethodsAmong 214 Chinese AR adults and 259 controls, tag SNP ?4071 A → G was genotyped and mRNA expression in peripheral blood was quantified by real-time PCR.ResultsEgr-1 mRNA expression was significantly higher in patients than controls (median of 0.23 vs 0.15 fold GAPDH expression; p < 0.001). Its expression was not associated with ? 4071 polymorphism. However, significant correlations were found between ? 4071 A → G with increased plasma total IgE (p = 0.028) and atopy (p = 0.030) in patients. Logistic regression confirmed the association (p = 0.034) with age and gender adjusted. Patients homozygous for the A allele had a 2.3-fold and 1.9-fold risks, respectively of having increased plasma total IgE and atopy than those G allele carriers.ConclusionsWe showed high levels of Egr-1 mRNA expression and demonstrated a significant association of polymorphism with increased plasma total IgE and atopy in AR patients. It may be useful to explore the pharmacogenetics of Egr-1 inhibitors.     

The −351A/G polymorphism of ESR1 is associated with risk of myocardial infarction but not with extreme longevity

BackgroundWomen live longer than men. Some possible reasons for this advantage are the protection provided by high concentrations of 17β-estradiol (E2) during the premenopausal period and polymorphic variants of the estrogen receptors (ERs), which mediate various cardiovascular functions of E2.MethodsWe tested whether the ?351A/G and ?397T/C polymorphisms of the ERα-encoding ESR1 were associated with extreme longevity. The genomic DNA of 148 centenarians (C), 414 young controls (Y), and 208 myocardial infarction patients (MI) was analyzed by RFLP-PCR.ResultsBoth polymorphisms were equally distributed in the Y, C, and in centenarians never diagnosed with MI (HC). In centenarians, none of these polymorphisms was associated with a particular lipid profile. The AA genotype of the ?351A/G polymorphism was less frequent in the C, HC and Y groups than in MI patients (p = 0.058, p = 0.021, and p = 0.004, respectively). In MI patients, the GG genotype of the ?351A/G polymorphism was associated with significantly lower mean total cholesterol, LDL, and HDL levels compared to the AG (p = 0.0194, p = 0.0213, and p = 0.0367, respectively) and AA genotypes (p = 0.0014, p = 0.0078, and p = 0.0448, respectively).ConclusionsThe ?351A/G ESR1 polymorphism might be associated with MI, but not with extreme longevity.     

Paraoxonase activity in athletes with depleted iron stores and iron-deficient erythropoiesis

ObjectiveThe aim of this study was to evaluate how conditions that precede anaemia (iron store depletion and iron-deficient erythropoiesis) affect human serum paraoxonase PON1 activity.Design and methodsBased on haemoglobin, transferrin saturation and serum ferritin values 119 athletes were divided into three groups: with iron depletion, with deficient erythropoiesis and controls. The following parameters were measured: paraoxonase activity towards paraoxon (POase) and diazoxon (DZOase), lipid hydroperoxides (LOOH), the pro-oxidant-antioxidant balance (PAB), red blood cells (RBC) and lipid status.ResultsSignificant differences were found between athletes with different stages of iron deficiency and controls with respect to PON 1 activity and oxidative stress status parameters (Wilks' Lambda = 0.712, F = 5.241, p < 0.001, η² = 0.156). There was no significant difference between the PON1 192 Q and R polymorphism distribution in the two groups of athletes with different stages of iron deficiency and controls (χ² = 1.086; p = 0.896). PON1 activity was positively correlated with RBCs, haemoglobin, transferrin saturation (p < 0.001) and ferritin (p = 0.037) and negatively correlated with LOOH (p = 0.044) in all three study groups.ConclusionsDeficient erythropoiesis in athletes contributes to impaired PON1 activity. In contrast, iron depletion, regardless of increased oxidative stress, does not affect PON1 activity.     

Association of alpha 2A adrenergic receptor gene (ADRΑ2A) polymorphism with irritable bowel syndrome,microscopic and ulcerative colitis

BackgroundAlpha 2 adrenergic receptors (α2 ARs) play a central role in the regulation of systemic sympathetic activity. Prejunctional alpha 2A adrenoceptor regulates through negative feedback at presynaptic nerve ending. A-1291 C > G polymorphism located in α2-adrenergic receptor gene (ADRΑ2A) has been identified. We investigated the possible association between 1291 C > G polymorphism in the promoter region of ADRΑ2A in clinical subtypes of IBS, ulcerative and microscopic colitis patients.MethodsThis prospective case control study included 92 patients with diarrhea predominant IBS (D-IBS), 44 with constipation predominant IBS (C-IBS), 15 with alternating diarrhea and constipation IBS (M-IBS), 75 ulcerative colitis (UC), 41 microscopic colitis (MC) and 100 healthy controls. The subjects were genotyped by using PCR amplification of the promoter region of ADRΑ2A gene followed by digestion with the restriction enzyme MspI. The study was approved by the institute ethical committee.ResultsA strong genotypic association was observed between α2A-1291 C > G polymorphism and D-IBS (χ² = 6.38, df = 2, p < 0.05). There was no significant difference in α2A-1291 C > G genotype and allele frequency between C-IBS, M-IBS, UC, MC cases and control subjects.ConclusionsA significant association was observed between α2A-1291C > G polymorphism and D-IBS. Thus, α2 AR gene may be a potential candidate involved in the pathophysiology of D-IBS.     

Functional vascular endothelial growth factor gene polymorphisms and diabetes: Effect on coronary collaterals in patients with significant coronary artery disease

BackgroundVascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. This study tested the association between functional VEGF + 405 C > G (rs2010963), ? 2578C > A (rs699947) polymorphisms, and coronary collaterals in patients with coronary artery disease (CAD).MethodThe collateral scoring system developed by Rentrop was used to classify 393 patients according to their collaterals as either “poor” (grades 0 and 1) or “good” (grades 2 and 3). Gene polymorphisms were analyzed by TaqMan assay.ResultsThe frequency of + 405C and ? 2578A alleles was higher in the good collaterals group (p = 0.007 and 0.005, respectively). For the + 405C > G allele, the odds ratio (OR) of good collaterals for CC to GG genotype was 2.54 (p = 0.003). For the ? 2578A allele, the OR of good collaterals for AA to CC genotype was 2.31 (p = 0.038). Univariate and logistic regression analysis found 2 polymorphisms in the additive model for associations with collateral development: + 405C > G (p = 0.005 and 0.010) and ? 2578C > A (p = 0.006 and 0.006). The VEGF + 405C > G polymorphism and DM revealed an interactive effect on collateral development (p = 0.027).ConclusionsThe VEGF + 405C > G and ? 2578C > A polymorphisms might be novel genetic factors affecting collateral development in Chinese patients.     

Clinical significance of Stratifin,ERα and PR promoter methylation in tumor and serum DNA in Indian breast cancer patients

Objectives:The objective of this study was to determine the concordance of promoter methylation of stratifin, ERα and PR in tumor and circulating DNA in breast cancer patients and their association with clinicopathological parameters and disease prognosis.Design and methods:Methylation specific PCR were carried out to investigate the promoter methylation status of stratifin, ERα and PR in tumor and circulating DNA in 100 breast cancer patients in a prospective study. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry.Results:Significant association was observed between promoter methylation of stratifin in tumors (61%) and paired sera (56%) (r = 0.78; p ≤ 0.001). Loss of stratifin expression was observed in 47% tumors and was associated with poor overall survival (p = 0.05). Significant correlation was observed between methylation status of ERα with PRB (p < 0.0001, OR = 20.8, 95% CI = 7.4–58.0) and stratifin (p = 0.003, OR = 2.0, 95% CI = 0.8–4.4).Conclusion:This study underscores the potential utility of serum DNA methylation of these genes as surrogate for tumor DNA methylation as a promising tool for cancer diagnosis.     

CYP11B2 gene haplotypes independently and in concurrence with aldosterone and aldosterone to renin ratio increase the risk of hypertension

ObjectivesAldosterone synthase produces aldosterone, which regulates electrolytes and thereby blood pressure. Polymorphisms in aldosterone-synthase gene (CYP11B2) may associate with heterogeneous aldosterone production and hypertension. Hence, we investigated ? 344T/C, Iw/Ic polymorphisms of CYP11B2, plasma renin activity (PRA) and aldosterone concentration (PAC).Design and methodsConsecutive ethnically-matched 450 hypertensive patients and 360 controls were screened by PCR-RFLP for genotypes and haplotypes; PRA and PAC were measured.ResultsThe Iw/Ic polymorphism distribution differed significantly between the two groups (LRT χ² = 15.8, df = 2, P = 0.000). The mutant allele-Ic and genotype-Ic/Ic were overrepresented in patients (35% versus 27% and 13% versus 7%). Overrepresentation of T-Ic haplotype in patients was identified as risk haplotype (P = 0.000). Patients had significantly higher PAC and aldosterone-to-renin ratio (ARR; P  = 0.000), which was Ic-allele dependent.ConclusionsThe haplotype T-Ic associated with hypertension susceptibility. Correlation between Ic-allele and raised ARR likely serve in hypertension management.     

Video laryngoscopy versus direct laryngoscopy for tracheal intubation during in-hospital cardiopulmonary resuscitation

AimTracheal intubation during cardiopulmonary resuscitation (CPR) is a high-risk procedure. Here, we investigated the efficacy of video laryngoscopy for tracheal intubation during CPR.MethodsData regarding tracheal intubation during CPR from in-hospital cardiac arrests occurring between January 2011 and December 2013 (n = 229) were prospectively collected and retrospectively analyzed.ResultsThe initial laryngoscopy method was video laryngoscopy in 121 patients (52.8%) and direct laryngoscopy in 108 patients (47.2%). The rate of successful intubation at the first attempt was higher with video laryngoscopy (71.9%; 87/121) than with direct laryngoscopy (52.8%; 57/108; p = 0.003). The rate of success at the first attempt was higher for experienced (73.0%; 84/115) than inexperienced operators, including residents (52.6%; 60/114; p = 0.001). Mortality at day 28 after CPR was not significantly different between patients with successful tracheal intubation at the first attempt and without (68.1% [98/144] vs. 67.1% [57/85]; p = 0.876). In multivariate logistic regression analysis, a predicted difficult airway (odds ratio [95% confidence interval] = 0.22 [0.10–0.49]; p < 0.001), intubation by an experienced operator (2.63 [1.42–4.87]; p = 0.002), and use of video laryngoscopy rather than direct laryngoscopy (2.42 [1.30–4.45]; p = 0.005) were independently associated with a successful tracheal intubation at the first attempt.ConclusionUse of video laryngoscopy during CPR from in-hospital cardiac arrest is independently associated with successful tracheal intubation at the first attempt.     

CYP1A1, CYP1A2 and CYBA gene polymorphisms associated with oxidative stress in COPD

BackgroundThe genetic susceptibility to chronic obstructive pulmonary disease (COPD) depends on detoxification and antioxidant enzymes, which detoxify cigarette smoke reactive components that, otherwise, generate oxidative stress.MethodsIn a case–control study of 346 subjects with and without COPD, we examined the polymorphisms 462Ile/Val, 3801T/C of CYP1A1, ?3860G/A of CYP1A2 and ?930A/G, 242C/T of CYBA individually or in combination and their contribution to oxidative stress markers by measuring malondialdehyde (MDA), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx).ResultsCOPD patients had significantly increased MDA concentration (p < 0.001) and decreased CAT activity, GSH concentration, GPx activity (p ≤ 0.01). The patients were over-represented by the alleles 462Val, 3801C of CYP1A1 and ?930G, 242C of CYBA (p < 0.001, p = 0.003, p = 0.030 and p = 0.031, respectively) and consequently the haplotypes of same alleles i.e. 462Val:3801C, 462Val:3801T and ?930G:242C (p = 0.048, p = 0.016 and p = 0.039, respectively). Similarly, CYP1A1 and CYP1A2 haplotypes, 462Val:3860G and 462Val:3801T:3860G were significantly over-represented (p = 0.001 and p = 0.003), respectively in patients. The same alleles-associated genotype-combinations between genes were more prevalent in patients. Of note, the genotypes, 462Ile/Val+Val/Val, 3801TC+CC of CYP1A1 and ?930AG+GG of CYBA associated with increased MDA concentration (p = 0.018, p = 0.045 and p = 0.017, respectively), decreased CAT activity (p < 0.0001, p = 0.080 and p < 0.0001, respectively) and GSH concentration (p < 0.0001, p = 0.0002 and p = 0.011, respectively) in patients.ConclusionThe identified alleles, its haplotypes and the genotype-combination along with increased oxidative stress, signify the importance in susceptibility to COPD.     

Kallikrein-related peptidase 13 (KLK13) gene expressional status contributes significantly in the prognosis of primary gastric carcinomas

ObjectivesGastric cancer is a fatal human malignancy with poor prognosis. Modifications in gene expression, including those of the kallikrein-related peptidase family, have been portrayed in gastric carcinogenesis. Given KLK13 involvement in human malignancies, we aimed to uncover its prognostic strength in stomach cancer.Design and methodsQuantitative analysis of KLK13 profiles was accomplished in human gastric cancer cells and in a statistically significant sample size of stomach tissue specimens with the development of the highly sensitive real-time PCR methodology.ResultsDecreased KLK13 expression was demonstrated in cancerous compared with their matching non-malignant pairs (p = 0.002) and in poorly differentiated gastric tumors (p = 0.029). KLK13-positive patients were shown to live considerably longer (p = 0.014) and with low risk of disease recurrences (p = 0.043).ConclusionsThis is the first study disclosing the possible clinical utility of KLK13 as a new tumor biomarker capable of predicting a favorable outcome for gastric cancer patients.     

Interleukin-1β genotype and circulating levels in cancer patients: Metastatic status and pain perception

ObjectivesProinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients.Design and methodsSerum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters.ResultsIL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p = 0.032, Mann–Whitney test) and presented a trend for lower levels of pain (p = 0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR = 4.074, p = 0.010, Pearson χ² test). Among the female patients presenting metastatic disease and carriers of the TT genotype we observed a trend to lower levels of IL1-β (p = 0.053, Pearson χ² test).ConclusionsOur results indicate that genetic variation at IL1-β gene may influence serum levels of IL1-β, with proportional consequences in cancer-related pain.     

Apolipoprotein M promoter polymorphisms alter promoter activity and confer the susceptibility to the development of type 1 diabetes

ObjectivesApolipoprotein M plays an important role in the formation of preβ-HDL and cholesterol efflux to HDL. In the present study, we investigate the potential association between the ApoM promoter polymorphisms and type 1 diabetes.Design and methodsThe study was conducted in Peking Union Medical College, Beijing, China and Karolinska Institutet, Stockholm, Sweden. Two populations, including 493 Han Chinese subjects (177 T1D patients/316 controls) and 225 Swedish (124/101), are enrolled in the present study. Three single nucleotide polymorphisms (SNP) C-1065A, T-855C and T-778C in the promoter region of the ApoM gene are genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol. Promoter activity was measured by reporter gene assay.ResultsSNP T-778C was strongly associated with T1D in both Han Chinese (p = 0.002, OR = 2.188, CI 95% = 1.338–3.581) and Swedish (p = 0.021, OR = 2.865, CI 95% = 1.128–7.278) populations. The luciferase activity of ?778C promoter was 1.41 times as high as that of ?778T promoter (9.90 ± 1.92 vs. 7.04 ± 0.76, p = 0.001).ConclusionsAllele C of SNP T-778C may increase promoter activity and confer the risk susceptibility to the development of T1D.     

Receptor for advanced glycation end products (RAGE) and glyoxalase I gene polymorphisms in pathological pregnancy

ObjectivesThe aim of the study was to analyze polymorphisms of receptor for advanced glycation end products (RAGE) gene, and glyoxalase I gene and soluble RAGE, sRAGE, in physiological and pathological pregnancy.Design and methodsPolymorphisms of RAGE gene (? 429 T/C, ? 374 T/A, 557 G/A, 2184 A/G) and glyoxalase I gene (A419C) and sRAGE serum levels were determined in 284 women with pathological and physiological pregnancy.ResultsNo differences in distribution of genotype and allelic frequencies of studied polymorphisms were found. GA genotype of RAGE 557 G/A polymorphism (known as Gly82Ser) is associated with lower sRAGE serum levels in healthy pregnant women compared to GG genotype (483 ± 104 vs. 692 ± 262 pg/mL, p = 0.008). sRAGE correlates negatively with ALT in patients with pregnancy intrahepatic cholestasis (r = ? 0.536, p = 0.05).ConclusionsWe did not show any association of RAGE and glyoxalase I gene polymorphisms with pathological pregnancy, however further studies are needed to confirm the results.     

Soluble receptor for advanced glycation end-products (sRAGE) and polymorphisms of RAGE and glyoxalase I genes in patients with pancreas cancer

ObjectivesThe receptor for advanced glycation end-products (RAGE) takes part in the pathogenesis of many diseases, including diabetes mellitus and cancer. AGE-precursors are detoxified by glyoxalase (GLO). sRAGE, soluble RAGE, is an inhibitor of pathological effects mediated via RAGE. The aim was to study sRAGE and polymorphisms of RAGE (AGER) and GLO genes in patients with pancreas cancer (PC).Design and MethodsThe studied group consisted of 51 patients with PC (34 with impaired glucose tolerance—IGT, 17 without IGT), 34 type 2 DM and 154 controls. For genetic analysis, the number of patients was increased to 170. Serum sRAGE was measured by ELISA and all polymorphisms (RAGE ?429T/C, ?374T/A, 2184A/G, Gly82Ser and GLO A419C) were determined by PCR-RFLP and confirmed by sequencing.ResultsSoluble RAGE is decreased in patients with PC compared to patients with DM and controls (975 ± 532 vs. 1416 ± 868 vs. 1723 ± 643 pg/mL, p < 0.001). Patients with PC and IGT have lower sRAGE levels compared to patients with PC without IGT (886 ± 470 vs. 1153 ± 616 pg/mL, p < 0.05). No relationship of sRAGE to the stage was found. We did not show any difference in allelic and genotype frequencies in all RAGE and GLO polymorphisms among the studied groups.ConclusionThis is the first study demonstrating decreased sRAGE in patients with pancreas cancer. Its levels are even lower than in diabetics and are lowest in patients with PC and IGT. Our study supports the role of glucose metabolism disorder in cancerogenesis. Further studies are clearly warranted, especially with respect to potential preventive and therapeutic implications.     

Soluble serum Klotho in diabetic nephropathy: Relationship to VEGF-A

ObjectivesBoth kidney expression and soluble serum Klotho are influenced by chronic kidney disease (CKD) and diabetes. Serum Klotho is a yet poorly explored biomarker. We describe, for the first time to our knowledge, serum Klotho in diabetic patients with CKD and its relationship to vascular endothelial growth factor A (VEGF-A).Design and methodsWe included 43 controls and 146 diabetic patients with different stages of CKD. Laboratory evaluation, urinary albumin/creatinine ratio (UACR), Klotho (ELISA), VEGF-A (ELISA) were performed.ResultsKlotho was 0.40(0.10–1.30) ng/mL in diabetic patients without CKD and 0.80(0.30–1.30) ng/mL in controls, p = 0.20; VEGF-A was higher in diabetic patients 73.85(57.32–119.00) pg/mL than in controls 43.20(30.1–65.9) pg/mL, p < 0.0001. Klotho increased with CKD stage: 0.2(0.10–0.40) ng/mL in CKD 1/2, 0.60(0.20–1.1) ng/mL in CKD 3/4 and 1.45(0.425–2.90) ng/mL in dialysis patients, p < 0.0001; it also increased with decreasing glomerular filtration rate (GFR). Klotho was lower in albuminuric (UACR > 30 mg/g) patients 0.20(0.10–0.70) ng/mL than in normoalbuminuric (UACR < 30 mg/g) ones 0.50(0.20–1.30) ng/mL, p = 0.03; lowest Klotho was found in microalbuminuric (UACR 30–300 mg/g) patients, p = 0.07. VEGF was lower in microalbuminuric patients but was not influenced by GFR. In diabetic patients but not in controls, Klotho correlated to VEGF-A (r = 0.29, p = 0.0003); in multiple regression VEGF-A was the only significant predictor of Klotho: b = 0.27, 95%CI (0.01–0.04), p = 0.001.ConclusionsIn diabetic patients, Klotho is decreased in early CKD and increases thereafter, paralleling reduced GFR. VEGF-A is higher in diabetic patients than in controls. Both Klotho and VEGF-A are decreased in the presence of microalbuminuria. In diabetes, Klotho strongly correlates to VEGF-A.     

High density lipoprotein-anionic peptide factor effect on reverse cholesterol transport in type 2 diabetic patients with and without coronary artery disease

ObjectivesTo verify if HDL3 Anionic Peptide Factor (HDL3-APF) is as an apolipoprotein that promotes the reverse cholesterol transport.Design and methodsWe investigated a possible association between plasma HDL3-APF concentration, cholesterol efflux from Fu5AH cells and cholesteryl ester transfer protein (CETP) activity in type 2 diabetic patients with coronary artery disease (CAD) (n = 36), those without CAD (n = 20), and 37 healthy subjects.ResultsPlasma APF concentrations were decreased in diabetics with CAD compared to controls (p < 0.01). Cellular cholesterol efflux was decreased in diabetics without and with CAD, (p < 0.01 and p < 0.001 respectively). CETP activity was significantly elevated in all patient groups. Multiple linear regression analysis shows that cholesterol efflux was independently and positively related only to APF concentrations in controls.ConclusionsAPF is likely to be a key independent factor for promoting cellular cholesterol efflux in healthy subjects. However this association is altered in type 2 diabetes.     

Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence

ObjectivesMatrix metalloproteinase (MMP)-1 degrades fibrillar collagens suggesting important role in vascular remodeling. Data about MMP-1 promoter polymorphisms and carotid atherosclerosis (CA) are scarce. The aim of this study was to evaluate association of MMP-1 genotypes/haplotypes with carotid plaque (CP) presence in Serbian population.Design and methodsStudy enrolled a total of 702 participants: 274 controls and 428 consecutive patients with CA who underwent carotid endarterectomy. MMP-1 polymorphisms ? 1607 1G/2G, ? 519 A/G and ? 340 T/C were genotyped by PCR and RFLP methods.ResultsIndividuals carrying MMP-1 ? 1607 2G allele had significantly increased allele dose-dependent risk for CP presence (1G1G vs. 1G2G vs. 2G2G; OR = 1; OR = 1.87 95% CI 1.29–2.07; OR = 3.49 95% CI 1.67–7.30, p = 0.0009, respectively). Compared to the referent haplotype 2G_? 1607-T_? 340-A_? 519, the haplotypes 1G_? 1607-T_? 340-A_? 519, 1G_? 1607-T_? 340-G_? 519 and 2G_? 1607-C_? 340-A_? 519 had statistically significant protective effect on CP presence (OR = 0.41, 95% CI 0.29–0.81, p = 0.01; OR = 0.56, 95% CI 0.44–0.89, p = 0.01; OR = 0.43, 95% CI 0.27–0.86, p = 0.02, respectively).ConclusionsMMP-1 ? 1607 G/2G polymorphism solely and specific haplotypes of three analyzed promoter polymorphisms are significantly and independently associated with occurrence of CP. Replication studies in other populations are needed.     

Polymorphisms of the NOS3 gene in Southern Chilean subjects with coronary artery disease and controls

BackgroundNitric oxide (NO) from the endothelium, produced by oxidation of l-arginine to l-citruline for the action at the endothelial nitric oxide synthase (eNOS) is considered an important atheroprotective factor. The 894G>T, ? 786T>C and 4a/4b polymorphic variants of the NOS3 gene have been implicated in the development of coronary artery disease (CAD). We investigated the association between occurrence of CAD documented by angiography and the 894G>T, ? 786T>C and 4a/4b polymorphisms of the NOS3 gene in Southern Chilean individuals.MethodsA total of 112 unrelated patients with diagnosis of CAD confirmed by angiography and 112 controls were included in this study. The 894G>T and ? 786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a/4b polymorphism just for PCR.ResultsThe genotype distribution and the relative allelic frequencies for the 3 variants investigated were not significantly different between CAD and control subjects (p = NS). Moreover, the odds ratio for CAD associated with the 894T (OR = 1.22, 95% CI 0.76–1.95), ? 786C (OR = 1.16, 95% CI 0.75–1.80) and 4a (OR = 0.97, 95% CI 0.48–1.95) variants failed to reach statistical significance.ConclusionThese findings suggest that the 894G>T, ? 786T>C and 4a/4b polymorphisms of the NOS3 were not associated with CAD in the studied subjects.     

Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus

ObjectivesTo find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran.Design and methodsThe MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric T2DM patients by PCR-RFLP.ResultsThe possession of both MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold (p = 0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is sufficient to increase the risk of macroalbuminuria in T2DM patients by 4.1 and 5.5 times (p = 0.027, and p = 0.006, respectively). The concomitant presence of both 677T and 1298C alleles act in synergy to increase the risk of macroalbuminuria by 20.4-fold (p < 0.001) and progression of DN from microalbuminuria to macroalbuminuria (OR = 4.73, p = 0.01).ConclusionBoth MTHFR 677T and 1298C alleles increased the susceptibility to the onset and progression of DN in Iranians with T2DM.     

Vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (NOS3) polymorphisms are associated with high relapse risk in childhood acute lymphoblastic leukemia (ALL)

BackgroundAngiogenesis has been shown as an important process in hematological malignancies. It consists in endothelial proliferation, migration, and tube formation following pro-angiogenic factors releasing, specially the vascular endothelial growth factor (VEGF), which angiogenic effect seems to be dependent on nitric oxide (NO). We examined the association among functional polymorphisms in these two angiogenesis related genes: VEGF (?2578C>A, ?1154G>A, and ?634G>C) and NOS3 (?786T>C, intron 4 b>a, and Glu298Asp) with prognosis of childhood acute lymphoblastic leukemia (ALL).MethodsThe genotypes were determined and haplotypes estimated in 105 ALL patients that were divided in 2 groups: high risk (HR) and low risk of relapse (LR) patients. In addition, event-free survival curves according to genotypes were assessed.ResultsThe group HR compared to the LR showed a higher frequency of the alleles ?2578C and ?634C and the haplotype CGC for VEGF (0.72 vs. 0.51, p < 0.008; 0.47 vs. 0.26, p < 0.008; and 42.1 vs. 14.5, p < 0.006; respectively) and a lower frequency of the haplotype CbGlu (0.4 vs. 8.8, p < 0.006), for NOS3.ConclusionPolymorphisms of VEGF and NOS3 genes are associated with high risk of relapse, therefore may have a prognostic impact in childhood ALL.