Circum-Mediterranean influence in the Y-chromosome lineages associated with prostate cancer in Mexican men: A Converso heritage founder effect?

Prostate cancer is the second most common neoplasia amongst men worldwide. Hereditary susceptibility and ancestral heritage are well-established risk factors that explain the disparity trends across different ethnicities, populations, and regions even within the same country. The Y-chromosome has been considered a prototype biomarker for male health. African, European, Middle Eastern, and Hispanic ancestries exhibit the highest incidences of such neoplasia; Asians have the lowest rates. Nonetheless, the contribution of ancestry patterns has been scarcely explored among Latino males. The Mexican population has an extremely diverse genetic architecture where all the aforementioned ancestral backgrounds converge. Trans-ethnic research could illuminate the aetiology of prostate cancer, involving the migratory patterns, founder effects, and the ethnic contributions to its disparate incidence rates. The contribution of the ancestral heritage to prostate cancer risk were explored through a case-control study (152 cases and 372 controls) study in Mexican Mestizo males. Seventeen microsatellites were used to trace back the ancestral heritage using two Bayesian predictor methods. The lineage R1a seems to contribute to prostate cancer (ORadjusted:8.04, 95%CI:1.41-45.80) development, whereas E1b1a/E1b1b and GHIJ contributed to well-differentiated (Gleason ≤ 7), and late-onset prostate cancer. Meta-analyses reinforced our findings. The mentioned lineages exhibited a connection with the Middle Eastern and North African populations that enriched the patrilineal diversity to the southeast region of the Iberian Peninsula. This ancestral legacy arrived at the New World with the Spanish and Sephardim migrations. Our findings reinforced the contribution of family history and ethnic background to prostate cancer risk, although should be confirmed using a large sample size. Nonetheless, given its complex aetiology, in addition to the genetic component, the lifestyle and xenobiotic exposition could also influence the obtained results.

The DEFB1 gene rs11362 A/G genetic variant is associated with risk of developing CAD: a case-control study.

BACKGROUND: In the present study, we evaluated whether DEFB1 gene polymorphisms are associated with the presence of coronary artery disease (CAD). METHODS: Two rs11362 A/G, and rs1800972 C/G gene polymorphisms of DEFB1 gene were genotyped by 5'exonuclease TaqMan assays in 219 patients with CAD and 522 control individuals. RESULTS: The distribution of rs1800972 C/G polymorphisms was similar in patients with CAD and healthy controls. Nonetheless, under the co-dominant, dominant, recessive, and additive models, the AA genotype of the rs11362 A/G polymorphism was associated with the risk of developing CAD (OR = 1.89 pCCo-Dom = 0.041, OR = 1.46, pCDom = 0.034, OR = 1.69, pCRes = 0.039, and OR = 1.37, pCAdd = 0.012, respectively). In addition, the linkage disequilibrium showed that the 'AG' haplotype was associated with an increased risk of developing CAD (OR = 1.23, p = 0.042). According, with the Genotype-Tissue Expression (GTEx) consortium data, the rs11362 AA genotype is associated with a low mRNA expression of the ß-defensin-1 in tissues, such as artery aorta, artery coronary, heart left ventricle, and heart atrial appendage (p < 0.001). CONCLUSION: This study demonstrates that rs11362 A/G polymorphism of the DEFB1 gene is involved in the risk of developing CAD, and with a low RNA expression of the ß-defensin-1 in heart tissue.

IFN-γ stimulates Paneth cell secretion through necroptosis mTORC1 dependent.

Immune mediators affect multiple biological functions of intestinal epithelial cells (IECs) and, like Paneth and Paneth-like cells, play an important role in intestinal epithelial homeostasis. IFN-γ a prototypical proinflammatory cytokine disrupts intestinal epithelial homeostasis. However, the mechanism underlying the process remains unknown. In this study, using in vivo and in vitro models we demonstrate that IFN-γ is spontaneously secreted in the small intestine. Furthermore, we observed that this cytokine stimulates mitochondrial activity, ROS production, and Paneth and Paneth-like cell secretion. Paneth and Paneth-like secretion downstream of IFN-γ, as identified here, is mTORC1 and necroptosis-dependent. Thus, our findings revealed that the pleiotropic function of IFN-γ also includes the regulation of Paneth cell function in the homeostatic gut.

Antineoplastic effect of compounds C14 and P8 on TNBC and radioresistant TNBC cells by stabilizing the K-Ras4BG13D/PDE6δ complex.

Introduction: Breast cancer (BC) is the leading cause of cancer-related deaths among women, with triple-negative breast cancer (TNBC) representing one of the most aggressive and treatment-resistant subtypes. In this study, we aimed to evaluate the antitumor potential of C14 and P8 molecules in both TNBC and radioresistant TNBC cells. These compounds were chosen for their ability to stabilize the complex formed by the overactivated form of K-Ras4BG13D and its membrane transporter (PDE6δ). Methods: The antitumor potential of C14 and P8 was assessed using TNBC cell lines, MDA-MB-231, and the radioresistant derivative MDA-MB-231RR, both carrying the K-Ras4B> G13D mutation. We investigated the compounds' effects on K-Ras signaling pathways, cell viability, and tumor growth in vivo. Results: Western blotting analysis determined the negative impact of C14 and P8 on the activation of mutant K-Ras signaling pathways in MDA-MB-231 and MDA-MB-231RR cells. Proliferation assays demonstrated their efficacy as cytotoxic agents against K-RasG13D mutant cancer cells and in inducing apoptosis. Clonogenic assays proven their ability to inhibit TNBC and radioresistant TNBC cell clonogenicity. In In vivo studies, C14 and P8 inhibited tumor growth and reduced proliferation, angiogenesis, and cell cycle progression markers. Discussion: These findings suggest that C14 and P8 could serve as promising adjuvant treatments for TNBC, particularly for non-responders to standard therapies. By targeting overactivated K-Ras and its membrane transporter, these compounds offer potential therapeutic benefits against TNBC, including its radioresistant form. Further research and clinical trials are warranted to validate their efficacy and safety as novel TNBC treatments.

An ivermectin - atorvastatin combination impairs nuclear transport inhibiting dengue infection in vitro and in vivo.

Dengue virus (DENV) uses cellular nuclear transport machinery to import some proteins into the nucleus. Recently, the non-structural protein 3 (NS3) of DENV was localized in the nucleus of infected cells; however, its nuclear import mechanism is still unknown. In this study, we demonstrate that Ivermectin (IVM) inhibits the nuclear localization of NS3 through the inhibition of the Importin α/ß1 pathway. We also report that Atorvastatin (ATV) can modulate the nuclear transport of NS3 protease and NS5 polymerase of DENV-2. On the other hand, we found that IVM and ATV treatments reduce the alteration of nuclear pore complex (NPC) proteins, and an IVM+ATV combination reduced DENV infection both in vitro and in vivo. Hence, we conclude that ATV transport inhibition is an additional antiviral effect of this drug, suggesting a potential anti-DENV therapy in combination with IVM.

Synergistic effect of antagonists to KRas4B/PDE6 molecular complex in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among all human cancers as it is highly resistant to chemotherapy. K-Ras mutations usually trigger the development and progression of PDAC. We hypothesized that compounds stabilizing the KRas4B/PDE6δ complex could serve as PDAC treatments. Using in silico approaches, we identified the small molecules C14 and P8 that reduced K-Ras activation in primary PDAC cells. Importantly, C14 and P8 significantly prevented tumor growth in patient-derived xenotransplants. Combined treatment with C14 and P8 strongly increased cytotoxicity in PDAC cell lines and primary cultures and showed strong synergistic antineoplastic effects in preclinical murine PDAC models that were superior to conventional therapeutics without causing side effects. Mechanistically, C14 and P8 reduced tumor growth by inhibiting AKT and ERK signaling downstream of K-RAS leading to apoptosis, specifically in PDAC cells. Thus, combined treatment with C14 and P8 may be a superior pharmaceutical strategy to improve the outcome of PDAC.

Cholesterol-Lowering Drugs as Potential Antivirals: A Repurposing Approach against Flavivirus Infections.

Flaviviruses, including Dengue (DENV), Zika (ZIKV), and Yellow Fever (YFV) viruses, represent a significant global health burden. The development of effective antiviral therapies against these viruses is crucial to mitigate their impact. This study investigated the antiviral potential of the cholesterol-lowering drugs atorvastatin and ezetimibe in monotherapy and combination against DENV, ZIKV, and YFV. In vitro results demonstrated a dose-dependent reduction in the percentage of infected cells for both drugs. The combination of atorvastatin and ezetimibe showed a synergistic effect against DENV 2, an additive effect against DENV 4 and ZIKV, and an antagonistic effect against YFV. In AG129 mice infected with DENV 2, monotherapy with atorvastatin or ezetimibe significantly reduced clinical signs and increased survival. However, the combination of both drugs did not significantly affect survival. This study provides valuable insights into the potential of atorvastatin and ezetimibe as antiviral agents against flaviviruses and highlights the need for further investigations into their combined therapeutic effects.

Distinct Transcriptional Profile of PDZ Genes after Activation of Human Macrophages and Dendritic Cells.

The PDZ (PSD95, Dlg and ZO-1) genes encode proteins that primarily function as scaffolds of diverse signaling pathways. To date, 153 PDZ genes have been identified in the human genome, most of which have multiple protein isoforms widely studied in epithelial and neural cells. However, their expression and function in immune cells have been poorly studied. Herein, we aimed to assess the transcriptional profiles of 83 PDZ genes in human macrophages (Mɸ) and dendritic cells (DCs) and changes in their relative expression during cell PRR stimulation. Significantly distinct PDZ gene transcriptional profiles were identified under different stimulation conditions. Furthermore, a distinct PDZ gene transcriptional signature was found in Mɸ and DCs under the same phagocytic stimuli. Notably, more than 40 PDZ genes had significant changes in expression, with potentially relevant functions in antigen-presenting cells (APCs). Given that several PDZ proteins are targeted by viral products, our results support that many of these proteins might be viral targets in APCs as part of evasion mechanisms. Our results suggest a distinct requirement for PDZ scaffolds in Mɸ and DCs signaling pathways activation. More assessments on the functions of PDZ proteins in APCs and their role in immune evasion mechanisms are needed.

Dual Antiplatelet Therapy Versus Antiplatelet Monotherapy Plus Oral Anticoagulation in Patients with Acute Coronary Syndrome and Coronary Artery Ectasia: Design and Rationale of OVER-TIME Randomized Clinical Trial.

INTRODUCTION: The optimal anti-thrombotic therapy to prevent recurrent ischemic events in patients with acute coronary syndrome and coronary artery ectasia (CAE) remains unclear. AIM: To assess the efficacy and safety of antiplatelet plus anticoagulant therapy versus dual antiplatelet therapy in patients with acute coronary syndromes and coronary artery ectasia. METHODS: OVER-TIME is an investigator initiated, exploratory, open label, single center, randomized clinical trial comparing dual antiplatelet therapy (acetyl-salicylic acid plus a P2Y12 inhibitor) with the combination of an antiplatelet monotherapy (a P2Y12 inhibitor) plus a low dose anticoagulant (rivaroxaban, 15mg oral dose) for the prevention of recurrent ischemic events among patients with CAE. We aim to enroll approximately 60 patients with CAE and acute coronary syndromes. After recruitment, patients are randomized to (a) standard of care (dual antiplatelet regimen) or (b) the combination of antiplatelet monotherapy and low dose anticoagulant. Patients will be followed for at least 12 months. The OVER-TIME study aims to assess the efficacy of the regimen in prevention of major cardiovascular events and its security in bleeding events in acute coronary syndromes among patients with CAE. Expected results and conclusions: OVER-TIME is the first randomized controlled trial to assess different antithrombotic strategies in patients with CAE and acute coronary syndrome, and its results will offer preliminary data for the prevention of major cardiovascular events and bleeding events in this group of patients. TRIAL REGISTRATION NUMBER: NCT05233124 (ClinicalTrials.gov), date of registration: February 10, 2022.

CASP1 Gene Polymorphisms and BAT1-NFKBIL-LTA-CASP1 Gene-Gene Interactions Are Associated with Restenosis after Coronary Stenting.

In the present study, we evaluated the association of the BAT1, NFKBIL, LTA, and CASP1 single nucleotide polymorphisms and the gene−gene interactions with risk of developing restenosis after coronary stenting. The allele and genotype determination of the polymorphisms (BAT1 rs2239527 C/G, NFKBIL1 rs2071592 T/A, LTA rs1800683 G/A, CASP1 rs501192 A/G, and CASP1 rs580253 A/G) were performed by 5'exonuclease TaqMan assays in 219 patients: 66 patients with restenosis and 153 without restenosis. The distribution of rs2239527 C/G, rs2071592 T/A, and rs1800683 G/A polymorphisms was similar in patients with and without restenosis. Nonetheless, under recessive (OR = 2.73, pCRes = 0.031) and additive models (OR = 1.65, pCAdd = 0.039), the AA genotype of the rs501192 A/G polymorphism increased the restenosis risk. Under co-dominant, dominant, recessive, and additive models, the AA genotype of the rs580253 A/G was associated with a high restenosis risk (OR = 5.38, pCCo-Dom = 0.003; OR = 2.12, pCDom = 0.031; OR = 4.32, pCRes = 0.001; and OR = 2.16, 95%CI: 1.33−3.52, pCAdd = 0.001, respectively). In addition, we identified an interaction associated with restenosis susceptibility: BAT1-NFKBIL1-LTA-CASP1 (OR = 9.92, p < 0.001). In summary, our findings demonstrate that the rs501192 A/G and rs580253 A/G polymorphisms, as well as the gene−gene interactions between BAT1-NFKBIL1-LTA-CASP1, are associated with an increased restenosis risk after coronary stenting.

Factorial design in the optimization and study 'in combo' of derivatives of imidazo[1,2-a]azines in the COX´s isoforms inhibition.

Background: Imidazo[1,2-a]azines with an acid group decrease inflammatory processes in murine models, and the effect has been attributed to the inhibition of COX enzymes. Results: The optimization of a series of imidazo[1,2-a]azines was performed using the reduced factorial design 23-1. The inhibitory effects of five acid derivatives of imidazo[1,2-a]azines and the standard drugs ibuprofen and indomethacin were evaluated in vitro on COX isoforms. It was observed that the different substituents provided different inhibition profiles, highlighting that the imidazo[1,2-a]pyridines are more active than the bioisosteric imidazo[1,2-a]pyrimidines. These results were analyzed using in silico docking to recognize the structural elements necessary for the inhibition of the targets. The IC50 values for COX1 and COX2 for the various compounds were as follows. COX1: 4a = 2.72 µM, 4b = 3.94 µM, 5a = 7.29µM, 5b = 63.26 µM, 6a = 12.93 µM, indomethacin = 0.13 µM, ibuprofen = 0.2 µM; COX 2: 4a = 1.89 µM, 4b = 2.39 µM, 5a = 8.08 µM, 5b = 41.15 µM, 6a = 5.86 µM, indomethacin = 0.09 µM, ibuprofen = 0.125 µM. Conclusion: Through factorial design it was possible to optimize the inhibitory response on therapeutic targets, obtaining molecule 4a as a result of factorial analysis.

Profiling of circulating chromosome 21-encoded microRNAs, miR-155, and let-7c, in down syndrome.

BACKGROUND: Down syndrome (DS) is the most common chromosomal survival aneuploidy. The increase in DS life expectancy further heightens the risk of dementia, principally early-onset Alzheimer's disease (AD). AD risk in DS is higher, considering that this population may also develop metabolic diseases such as obesity, dyslipidemias, and diabetes mellitus. The extra genetic material that characterizes DS causes an imbalance in the genetic dosage, including over-expression of AD's key pathophysiological molecules and the gene expression regulators, the microRNAs (miRNAs). Two miRNAs, chromosome 21-encoded, miR-155, and let-7c, are associated with cognitive impairment and dementia in adults; but, expression dynamics and relationship with clinical variables during the DS's lifespan had remained hitherto unexplored. METHODS: The anthropometric, clinical, biochemical, and profile expression of circulating miR-155 and let-7c were analyzed in a population of 52 control and 50 DS subjects divided into the young group (Aged ≤20 years) and the adult group (Aged ≥21 years). RESULTS: The expression changes for miR-155 were not significant; nevertheless, a negative correlation with HDL-Cholesterol concentrations was observed. Notably, let-7c was over-expressed in DS from young and old ages. CONCLUSION: Overall, our results suggest that let-7c plays a role from the early stages of DS's cognitive impairment while overexpression of miR-155 may be related to lipid metabolism changes. Further studies of both miRNAs will shed light on their potential as therapeutic targets to prevent or delay DS's cognitive impairment.

Y chromosome diversity in Aztlan descendants and its implications for the history of Central Mexico.

Native Mexican populations are crucial for understanding the genetic ancestry of Aztec descendants and coexisting ethnolinguistic groups in the Valley of Mexico and elucidating the population dynamics of the prehistoric colonization of the Americas. Mesoamerican societies were multicultural in nature and also experienced significant admixture during Spanish colonization of the region. Despite these facts, Native Mexican Y chromosome diversity has been greatly understudied. To further elucidate their genetic history, we conducted a high-resolution Y chromosome analysis with Chichimecas, Nahuas, Otomies, Popolocas, Tepehuas, and Totonacas using 19 Y-short tandem repeat and 21 single nucleotide polymorphism loci. We detected enormous paternal genetic diversity in these groups, with haplogroups Q-MEH2, Q-M3, Q-Z768, Q-L663, Q-Z780, and Q-PV3 being identified. These data affirmed the southward colonization of the Americas via Beringia and connected Native Mexicans with indigenous populations from South-Central Siberia and Canada. They also suggested that multiple population dispersals gave rise to Y chromosome diversity in these populations.

A randomized controlled trial of lung ultrasound-guided therapy in heart failure (CLUSTER-HF study).

BACKGROUND: Lung ultrasound (LUS) has emerged as a new tool for the evaluation of congestion in heart failure (HF); incorporation of LUS during follow-up may detect congestion earlier and prompt interventions to prevent hospitalizations. The aim of this study was to test the hypothesis that the incorporation of LUS during follow-up of patients with HF may reduce the rate of adverse events compared with usual care. METHODS: In this single-blinded, randomized controlled trial, patients were randomized into an LUS-guided arm or control arm. Patients were followed in 4 prespecified visits during a 6-month period. LUS was performed in every patient visit in both groups; however, LUS results were available for the treating physician only in the LUS group. The primary outcome was the composite of urgent HF visits, rehospitalization for worsening HF, and death from any cause. RESULTS: One hundred twenty-six patients were randomized to either LUS (n = 63) or control (n = 63) (age 62.5 ±â€¯10 years, median left ventricular ejection fraction 31%). The primary end point occurred in 30 (47.6%) patients in the control group and 20 (31.7%) patients in the LUS group (P = .041). LUS-guided treatment was associated with a 45% risk reduction in the primary end point (hazard ratio 0.55, 95% CI 0.31-0.98, P = .044), mainly driven by a reduction in urgent HF visits (hazard ratio 0.28, 95% CI 0.13-0.62, P = .001). No significant differences in rehospitalizations for HF or death were found. CONCLUSIONS: Incorporation of LUS into clinical follow-up of patients with HF significantly reduced the risk of urgent visits for worsening HF.

Histological and Mechanical Behavior of INC 01 and 02 Bare Metal Stents Against a Commercial Stent: A Preclinical Study in a Porcine Model.

BACKGROUND: PCI is an expensive procedure in our population and it implies a huge cost for the institutions and National Health Service. AIM OF THE STUDY: The main objective was to evaluate the technical and biological success of two stents designed in Mexico. METHODS: Ten York pigs, 4-6 months of age, underwent implantation of the bare metal INC-01 (10 stents) and INC-02 (6 stents) coronary stent in addition to a conventional commercial stent (10 stents). Technical success was evaluated immediately with angiography and Intravascular Ultrasound IVUS, continued by a mean follow-up of 4 month and a final angiographic, IVUS and histological evaluation. RESULTS: Initial technical success, angiography and IVUS between the three stents were not significant. One stent presented restenosis in follow-up (commercial stent), but all other stents presented excellent clinical outcome, satisfactory angiographic and IVUS results. Inflammation, proliferation and endothelialization between the stents had no major differences in histological analysis in a mean of 4 months follow-up. CONCLUSIONS: In this pig model, the INC 01 and INC 02 stents showed the same delivering technical success, angiographic and IVUS features, biological and histological response compared to commercial last generation stents.

Use of STAT6 Phosphorylation Inhibitor and Trimethylglycine as New Adjuvant Therapies for 5-Fluorouracil in Colitis-Associated Tumorigenesis.

Colorectal cancer (CRC) is one of the most widespread and deadly types of neoplasia around the world, where the inflammatory microenvironment has critical importance in the process of tumor growth, metastasis, and drug resistance. Despite its limited effectiveness, 5-fluorouracil (5-FU) is the main drug utilized for CRC treatment. The combination of 5-FU with other agents modestly increases its effectiveness in patients. Here, we evaluated the anti-inflammatory Trimethylglycine and the Signal transducer and activator of transcription (STAT6) inhibitor AS1517499, as possible adjuvants to 5-FU in already established cancers, using a model of colitis-associated colon cancer (CAC). We found that these adjuvant therapies induced a remarkable reduction of tumor growth when administrated together with 5-FU, correlating with a reduction in STAT6-phosphorylation. This reduction upgraded the effect of 5-FU by increasing both levels of apoptosis and markers of cell adhesion such as E-cadherin, whereas decreased epithelial-mesenchymal transition markers were associated with aggressive phenotypes and drug resistance, such as ß-catenin nuclear translocation and Zinc finger protein SNAI1 (SNAI1). Additionally, Il-10, Tgf-ß, and Il-17a, critical pro-tumorigenic cytokines, were downmodulated in the colon by these adjuvant therapies. In vitro assays on human colon cancer cells showed that Trimethylglycine also reduced STAT6-phosphorylation. Our study is relatively unique in focusing on the effects of the combined administration of AS1517499 and Trimethylglycine together with 5-FU on already established CAC which synergizes to markedly reduce the colon tumor load. Together, these data point to STAT6 as a valuable target for adjuvant therapy in colon cancer.

ALOX5, LPA, MMP9 and TPO gene polymorphisms increase atherothrombosis susceptibility in middle-aged Mexicans.

Atherothrombosis is the cornerstone of cardiovascular diseases and the primary cause of death worldwide. Genetic contribution to disturbances in lipid metabolism, coagulation, inflammation and oxidative stress increase the susceptibility to its development and progression. Given its multifactorial nature, the multiloci studies have been proposed as potential predictors of susceptibility. A cross-sectional study was conducted to explore the contribution of nine genes involved in oxidative stress, inflammatory and thrombotic processes in 204 subjects with atherothrombosis matched by age and gender with a healthy group (n = 204). To evaluate the possibility of spurious associations owing to the Mexican population genetic heterogeneity as well as its ancestral origins, 300 unrelated mestizo individuals and 329 Native Americans were also included. ALOX5, LPA, MMP9 and TPO gene polymorphisms, as well as their multiallelic combinations, were twice to four times more frequent in those individuals with clinical manifestations of atherothrombosis than in the healthy group. Once adjusting for population stratification was done, these differences remained. Our results add further evidence on the contribution of ALOX5, LPA, MMP9 and TPO polymorphisms to atherothrombosis development in the middle-aged group, emphasizing the multiethnic studies in search of gene risk polymorphisms.

Clinical Association of White Matter Hyperintensities Localization in a Mexican Family with Spastic Paraparesis Carrying the PSEN1 A431E Mutation.

Presenilin 1 gene (PSEN1) mutations are the most common cause of familial Alzheimer's disease (FAD). One of the most abundant FAD mutations, PSEN1 A431E, has been reported to be associated with spastic paraparesis in about half of its carriers, but the determining mechanisms of this phenotype are still unknown. In our study we characterized three A431E mutation carriers, one symptomatic and two asymptomatic, from a Mexican family with a history of spastic paraparesis in all of its affected members. At cognitive assessment and MRI, the symptomatic subject showed an atypical non-amnestic mild cognitive impairment with visuospatial deficits, olfactory dysfunction and significant parieto-occipital brain atrophy. Furthermore, we found several periventricular white matter hyperintensities whose progression pattern and localization correlated with their motor impairment, cognitive profile, and non-motor symptoms. Together, our data suggests that in this family the A431E mutation leads to a divergent neurological disorder in which cognitive deterioration was clinically exceeded by motor impairment and that it involves early glial and vascular pathological changes.

Ecocardiograma de contraste con burbujas en ablación septal con alcohol / Bubble contrast echocardiography for alcohol septal ablation

No disponible

miR-196a2 (rs11614913) polymorphism is associated with coronary artery disease, but not with in-stent coronary restenosis.

OBJECTIVE: The aim of the study was to evaluate the association of miRNA-146a G/C (rs2910164), and miRNA-196a2 C/T (rs11614913) polymorphisms with the presence of coronary artery disease (CAD) and/or restenosis in patients with coronary stent. MATERIALS AND METHODS: The polymorphisms were determined in 218 patients with CAD who underwent coronary artery stenting (66 with restenosis and 152 without restenosis) and 611 healthy controls using 5' exonuclease TaqMan assays. RESULTS: The distribution of both polymorphisms was similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant and additive genetic models, the T allele of the miRNA-196a2 C/T (rs11614913) polymorphism was associated with increased risk of CAD (OR = 2.18, Pco-dom = 0.006, OR = 1.86, Pdom = 0.002, and OR = 1.52, Padd = 0.002, respectively). All models were adjusted for age, type 2 diabetes mellitus, dyslipidemia, hypertension and smoking habit. The "GT" haplotype was associated with increased risk of developing CAD (OR = 1.36, P = 0.046). CONCLUSIONS: Our data suggests that the T allele of the miRNA-196a2 C/T (rs11614913) polymorphism is associated with the risk of developing CAD, but no association with restenosis was observed.