ABSTRACT
The incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) is constantly increasing, becoming a significant health problem. CTLA-4 is a critical immune checkpoint, and it has been suggested that a variant of variable-number tandem repeat in the 3'-UTR of its gene, known as (AT)n, may be associated with a higher susceptibility to some cancers; however, little is known about genetic variants of the CTLA-4 gene in NMSC. To establish the association of this genetic variant in the CTLA-4 gene with the susceptibility of NMSC carcinogenesis in the Western Mexican population, samples from 150 BCC patients, 150 SCC patients, and 150 healthy individuals as the reference group (RG) were analyzed by endpoint PCR, followed by electrophoresis to genotype the samples. We found that the short-repeat 104/104 bp genotype may be a risk factor for BBC carcinogens (OR = 2.92, p = 0.03), whereas the long-repeat 106/106 bp genotype may be a protective factor for both BCC (OR = 0.13, p = 0.01) and SCC (OR = 0.32, p = 0.01) susceptibility. Our results show that in the Western Mexican population, long-repeat (AT)n variants in the CTLA-4 gene are associated with a protective factor in BCC and SCC. In contrast, short repeats are associated with a risk factor.
ABSTRACT
Interleukin-10 (IL-10) is an immunomodulatory cytokine that plays a pivotal role in the pathogenesis of acute coronary syndromes (ACS). Here, we evaluated the role of IL10 promoter variants as markers for ACS susceptibility in Western Mexican patients as well as its association with IL10 mRNA and IL-10 plasma levels. Three promoter variants (- 1082 A > G, - 819 T > C and - 592 A > C) were analyzed in 300 ACS patients and 300 control group (CG) individuals. IL10 relative gene expression was evaluated in peripheral blood mononuclear cells (PBMC) and IL-10 levels were quantified in plasma. The allelic, genotypic and haplotypic frequencies did not show significant differences between groups. ACS patients had sevenfold higher mRNA IL10 level compared to CG (p = 0.0013). Homozygous C/C carriers in both - 819 T > C and - 592 A > C variants had 0.4-fold higher IL10 mRNA expression than heterozygous and polymorphic allele homozygous genotypes (p = 0.0357) in ACS group. There were significant differences in plasma IL-10 levels in CG and ACS group (1.001 vs 1.777 pg/mL, p = 0.0051). The variants were not markers of susceptibility to ACS in Western Mexican individuals. ACS patients showed higher IL10 expression than CG individuals which could be mediated by - 819 T > C and - 592 A > C variants and pharmacotherapy.
Subject(s)
Acute Coronary Syndrome , Genetic Predisposition to Disease , Interleukin-10 , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Humans , Interleukin-10/genetics , Interleukin-10/blood , Acute Coronary Syndrome/genetics , Acute Coronary Syndrome/blood , Male , Female , Middle Aged , Aged , Case-Control Studies , Genotype , Alleles , Biomarkers/blood , Mexico , Leukocytes, Mononuclear/metabolism , Gene Frequency , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
Acute kidney injury (AKI) is a highly prevalent and a critical complication of cardiac surgery (CS). Serum lactate (sLac) levels have consistently shown an association with morbimortality after CS. We performed a cross-sectional study including 264 adult patients that had a cardiac surgery between January and December 2020. Logistic regression analysis was performed to determine factors associated with AKI development. We measured the postoperative levels of sLac for all participants immediately after CS (T0) and at 4 h (T4) after the surgical intervention. A linear regression model was used to identify the factors influencing both sLac metrics. We identified four risk predictors of AKI; one was preoperative (atrial fibrillation), one intraoperative (cardiopulmonary bypass time), and two were postoperative (length of hospital stay and postoperative sLac). T0 and T4 sLac levels were higher among CS-AKI patients than in Non-CS-AKI patients. Postoperative sLac levels were significant independent predictors of CSA-AKI, and sLac levels are influenced by length of hospital stay, the number of transfused packed red blood cells, and the use of furosemide in CS-AKI patients. These findings may facilitate the earlier identification of patients susceptible to AKI after CS.
ABSTRACT
BACKGROUND: Some cytokines are strongly implicated in the development of squamous cell carcinoma (SCC) such as the Macrophage migration inhibitory factor (MIF). The haplotype -794 (CATT)5-8 /-173G>C in MIF gene polymorphisms has been associated with some types of cancer. The aim of this study is to establish the possible association between the presence of this haplotype in the MIF gene and its subsequent soluble levels with the susceptibility of SCC in western Mexican population. METHODS: This study included 175 SCC patients and 175 age-sex-matched individuals as a reference group (RG) from western Mexico. Genomic DNA was extracted from peripheral blood leukocytes. Polymorphisms were genotyped by endpoint PCR and PCR-RFLP, and the determination of MIF serum levels was measured by ELISA. Clinical characteristics were evaluated by a group of dermatologists. RESULTS: Analysis of [-794(CATT)5-8 /-173G>C] MIF gene polymorphisms showed that the 5C (OR = 2.7, p = 0.02) and the 7G (OR = 3.39, p < 0.01) haplotypes are associated with susceptibility in SCC. MIF soluble levels in SCC patients showed a median of 13.93 ng/mL, whereas the reference group showed 6.000 ng/mL. CONCLUSIONS: Our findings suggest that 5C and 7G [-794(CATT)5-8 /-173G>C] MIF gene haplotypes are associated with susceptibility to SCC and that SCC patients present increased soluble levels of MIF.
Subject(s)
Carcinoma, Squamous Cell , Macrophage Migration-Inhibitory Factors , Skin Neoplasms , Humans , Haplotypes , Carcinoma, Squamous Cell/genetics , Mexico , Genetic Predisposition to Disease , Skin Neoplasms/genetics , Polymorphism, Genetic , Macrophage Migration-Inhibitory Factors/genetics , Intramolecular Oxidoreductases/geneticsABSTRACT
Introduction: The increased risk of myocardial infarction (MI) in type 2 diabetes mellitus (T2DM) is well documented. Polymorphisms in APOA1 and APOB genes allow us to identify new genetic markers in the Mexican population with T2DM and MI. Material and methods: We studied 135 patients with DMT2 and MI (DI); another 85 non-infarcted diabetic individuals with DMT2 but without previous ischemic events (NID) and 242 healthy subjects (HS). All three groups were selected with the aim to investigate the association between the polymorphisms and infarction when T2DM is present or absent. Results: -75 G>A polymorphism: Differences were found in genotype distribution between DI and NID individuals (OR = 2.01, 95% CI: 1.117-3.623, p = 0.019) with an increased risk for A in the dominant model (OR = 1.77, 95% CI: 1.020-3.084, p = 0.042); also concentrations of ApoA-I for A/A were lower in comparison with G/A (p = 0.038) and LDL-C and HDL-C levels were lower in G/A compared to G/G carriers. 83 C>T polymorphism of APOA1: For DI individuals, HDL-C was lower in T/T compared to C/C and triglyceride levels were lower in C/T compared to C/C carriers. Conclusions: The -75 G>A APOA1 polymorphism could be considered as a susceptibility factor for myocardial infarction in individuals with T2DM and 2488 C>T APOB polymorphism is associated with changes in HDL-C and LDL-C and triglycerides in the same group.
ABSTRACT
BACKGROUND: Atherosclerosis plays an important role in the pathophysiology of acute coronary syndrome (ACS). CD36 is a scavenger receptor involved in lipid metabolism. Some single-nucleotide variants in the non-coding region could indirectly alter the expression and the function of the protein. OBJECTIVE: The aim of this study was to investigate the gene and protein expression associated with CD36 variants (rs1194182;C > G; rs1049654;C > A, rs1334512;G > T, and rs3211892;G > A) in ACS patients from the western Mexican population. METHODS: We recruited 310 ACS patients and 308 subjects in the control group (CG). Genotyping was determined by TaqMan SNP genotyping assays. CD36 expression at the mRNA level was quantified by TaqMan gene expression assays. Soluble CD36 (sCD36) was measured by enzyme-linked immunosorbent assay. RESULTS: We show that rs1194182G > C variant provides a protective effect with a 1.7-fold lower susceptibility to develop ACS (p = 0.03); however, this association was masked by diabetes and dyslipidemia. We observed a higher sCD36 concentration in patient with ST-segment elevation myocardial infarction (STEMI) compared with patients with unstable angina (UA) (p = 0.038). Likewise, in diabetic patients versus non-diabetic (p < 0.001). We observed in patients an increase in CD36 mRNA expression (1.91 times higher) than in the CG (p = 0.02). CONCLUSION: The rs1194182 seems to be associated with diabetes in a risky manner, in ACS patients and protective for dyslipidemia in both groups. The concentration of sCD36 seems to be associated with the clinical spectrum of the ACS patients and the presence of diabetes, since patients with STEMI present significantly elevated level compared with UA.
Subject(s)
Acute Coronary Syndrome , CD36 Antigens , Dyslipidemias , ST Elevation Myocardial Infarction , Acute Coronary Syndrome/genetics , Angina, Unstable/genetics , CD36 Antigens/genetics , Gene Expression , Humans , RNA, Messenger/genetics , ST Elevation Myocardial Infarction/geneticsABSTRACT
Apolipoprotein B (APOB) is associated with the development of atherosclerosis and consequently in the acute coronary syndrome (ACS) physiopathology. Single number variants (SNVs) in apolipoprotein B gene (APOB) influence over the susceptibility for this syndrome. The aim of this study was to determine the impact of the rs1469513, rs673548, rs676210, and rs1042034 SNVs and serum levels of APOB in the risk of ACS in a population from western Mexico. We included 300 patients in the group of cases (ACSG) and 300 individuals in the control group (CG). APOB levels were evaluated by immunonephelometry, and SNVs were genotyped with TaqMan probes. We found significant allelic and genotypic differences between groups for rs673548 and rs676210 (OR = 1.33, p=0.030, OR = 2.69, p < 0.001) and rs1042034 (OR = 0.50, p=0.037) SNVs. We found a risk haplotype TAGT (OR: 2.14, IC 1.50-3.04, p < 0.001). Our findings support a significant risk association between rs673548 and rs676210 variants for ACS; meanwhile, rs1042034 could be considered protective factor in a western Mexican population. Also, in this population, haplotype TAGT may confer 2.14 times a higher risk. APOB serum levels were compared by genotype variants in both groups without any significant statistical difference.
Subject(s)
Acute Coronary Syndrome , Acute Coronary Syndrome/genetics , Apolipoproteins B/genetics , Humans , Mexico/epidemiology , Nucleotides , Polymorphism, Single Nucleotide/geneticsABSTRACT
Basal cell carcinoma (BCC) is the most common dermatological neoplasms in Caucasian populations. In Mexico, a prevalence of 3.9 per 1000 habitants is estimated. Recently, the macrophage migration inhibitory factor (MIF) has been related to different types of cancer. Therefore, this study aimed to investigate the genetic association of haplotypes of [-794(CATT)5-8/-173G>C]MIF gene polymorphisms and its soluble levels in BCC. A total of 360 individuals were recruited for the study, that is, 180 of the total amounts were patients with BCC histologically confirmed and the remaining 180 individuals were identified as control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP (restriction fragment length polymorphism), and MIF serum levels were measured by ELISA kit. A borderline difference was found between the 55 genotype and the susceptibility to BCC (5.6% vs 1.7% in BCC and CS, respectively, OR=3.7 and p=0.04). Furthermore, the haplotype 7G showed a significant association with BCC (p=0.02, OR=1.99). Concerning MIF soluble levels, patients with BCC showed a media of 2.1 ng/mL and CS showed 4.4 ng/mL, the comparison between groups was significant (p<0.01). Our findings suggest that the 55 genotype and the haplotype 7G are associated with the susceptibility to BCC; furthermore, a significant difference was found between MIF soluble levels in both study groups.
Subject(s)
Carcinoma, Basal Cell/genetics , Haplotypes , Intramolecular Oxidoreductases/genetics , Macrophage Migration-Inhibitory Factors/genetics , Skin Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Mexico , Middle Aged , Polymorphism, GeneticABSTRACT
Background: C-reactive protein (CRP) is involved in inflammatory pathways that are associated with the onset and progression of type 2 diabetes mellitus (T2DM) as well as an increased risk of an acute coronary syndrome (ACS). This research aimed to evaluate the potential association of the genetic variants -717T>C, 1444G>A, and 1846 C > T of CRP gene on CRP levels, ACS, and T2DM in participants from Western Mexico. Methods: Six hundred three participants were studied: (1) control group (CG); (2) ACS participants classified as unstable angina (UA), myocardial infarction without ST-segment elevation (NSTEMI), and myocardial infarction with ST-segment elevation (STEMI); (3) T2DM Participants; and (4) ACS plus T2DM participants (ACS+T2DM). Genetic variants were genotyped using allelic discrimination with TaqMan® probes, and high-sensitivity CRP (hs-CRP) was measured by Turbidimetry. Results: TAC haplotype frequency was significantly higher in ACS+T2DM versus CG and versus ACS participants (odds ratio [OR] = 2.774, P = 0.017 and OR = 3.479, P = 0.020, respectively). hs-CRP levels were especially higher for ACS and for ACS+T2DM participants with respect to CG and T2DM (with P < 0.0001). We observed higher hs-CRP levels in NSTEMI and STEMI versus UA in ACS scenario (P = 0.001, P = 0.027, respectively) and for ACS+T2DM scenario (P = 0.0001, P = 0.002, respectively). Conclusion: hs-CRP level fluctuations are related to the presence of T2DM and the presence and severity of ACS. Very high levels (>10 mg/L) are a risk marker of cardiovascular complications. Our results demonstrate a possible relationship between TAC haplotype and an increased risk for T2DM and ACS.
Subject(s)
Acute Coronary Syndrome , Diabetes Mellitus, Type 2 , Myocardial Infarction , Non-ST Elevated Myocardial Infarction , ST Elevation Myocardial Infarction , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/epidemiology , Acute Coronary Syndrome/genetics , Angina, Unstable , C-Reactive Protein , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Haplotypes , Humans , Mexico/epidemiology , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Myocardial Infarction/geneticsABSTRACT
METHODS: This is a retrospective study including male and female patients aged ≥18 years who were diagnosed with ACS. The collected data included demographic characteristics, risk factors, medications, electrocardiograms, surgical procedures, and in-hospital deaths. RESULTS: There are at least 20% more diagnoses of ST-segment elevation myocardial infarction in this hospital compared to the latest national reports in Mexico. The most common risk factors were type 2 diabetes mellitus, hypertension, smoking, and dyslipidaemia. Diabetic patients with a clinical history of percutaneous coronary intervention had a higher risk of non-ST-segment elevation myocardial infarction than nondiabetics (OR: 2.34; p=0.013), also smoking patients with previous heart surgery than nonsmokers (OR: 7.73; p=0.0007). The average in-hospital mortality was 3.6% for ACS. CONCLUSIONS: There is a higher percentage of coronary interventionism and improvement in pharmacological treatment, which is reflected in lower mortality. The substantial burden of T2DM could be related to a higher number of cases of STEMI. Diabetics with precedent percutaneous coronary intervention and smokers with previous heart surgery have an increased risk of subsequent infarction.
ABSTRACT
INTRODUCTION: Multiple sclerosis is an inflammatory disease, where fibrin deposition and the impairment in its degradation have been shown to play an important role in the demyelination process. Tissue plasminogen activator (tPA) is a serine protease that enhances the conversion of plasminogen into its active form plasmin, the principal tPA inhibitor is the PAI-1. Several PAI-1 polymorphisms impact its gene expression and protein activity. Furthermore, the aim of this study was to investigate the association between the - 844 G>A, HindIII C>G, and 4G/5G PAI-1 polymorphisms and susceptibility to MS. MATERIAL AND METHODS: The study group included 400 Mexican mestizo subjects: 200 unrelated patients and 200 unrelated individuals identified as control subjects. The analysis of PAI-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: A significant association was found between the CG genotype of the HindIII C>G PAI-1 polymorphism and susceptibility to MS (OR = 1.58, p = 0.03); moreover, the frequency of 5G allele and 5G/5G genotype of the 4G/5G PAI-1 polymorphism was statistically significant (OR = 1.36 and p = 0.04 and OR = 2.43 and p = 0.02, respectively). With respect to the relation between the scores of progression (EDSS) and severity (MSSS), no association was found between EDSS and genotypes of the PAI-1 polymorphisms analyzed. Regarding MSSS, male that carries genotype GA of the -844 G>A and genotype 4G/5G of the 4G/5G PAI-1 polymorphisms showed a significant association with an increase of media of MSSS in comparison with females (p = 0.01 in both cases).
Subject(s)
Genetic Predisposition to Disease , Multiple Sclerosis/genetics , Plasminogen Activator Inhibitor 1/genetics , Polymorphism, Genetic , Adult , Disease Progression , Female , Genotype , Humans , Inflammation/genetics , Male , Mexico/epidemiology , Odds Ratio , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Sex Factors , Tissue Plasminogen Activator/metabolismABSTRACT
Background and aim: Presence of metabolic syndrome (MS) in patients with type 2 diabetes mellitus (T2DM) involves an increased risk of cardiovascular disease and death. Markers such as ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios have been used to predict this risk with conflicting results. The study objective was to establish the relationship between the apoB/apoA1 and non-HDL-cholesterol/HDL-cholesterol ratios and MS in T2DM patients from a Madrid (Spain) district. Patients and methods: One hundred patients with T2DM who attended University Hospital Infanta Leonor (Vallecas, Madrid, Spain) between January 2014 and June 2017 were enrolled. A blood sample was taken every 6 months from all patients to measure the different lipid parameters and to calculate ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. A Mann-Whitney's U test to compare means and a Spearman's correlation test for correlations between variables were used, and a multivariate regression analysis was performed to determine the association between MS and the ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. Values of p < 0.05 were considered significant. Results: Associations were found between MS and ApoA1 (R2 = 0.164, p = 0.028), ApoB/ApoA1 (R2 = 0.187, p = 0.001), and non-HDL-cholesterol/HDL-cholesterol (R2= 0.269, p = 0.0001) ratios and, in women with MS, between ApoB/ApoA1 ratio and ischemic cardiomyopathy (IC) (R2 = 0.160, p = 0.032). Associations remained after adjusting for comorbidities and risk factors. Conclusions: In the T2DM patients studied, MS was independently associated to ApoA1 and the ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. Both ratios were better predictors of MS in T2DM subjects that its components alone. The ApoB/ApoA1 ratio could be used as a cardiovascular risk marker in women with MS
Antecedentes: La presencia del síndrome metabólico (MetS) en pacientes con diabetes mellitus tipo 2 (T2DM) conlleva mayor riesgo de enfermedad cardiovascular y muerte. Se han utilizado marcadores para predecir este riesgo, como los índices ApoB/ApoA1 y no-HDL-C/HDL-C, pero con resultados controvertidos. El objetivo ha sido determinar las relaciones entre los índices ApoB/ApoA1 y no-HDL-C/HDL-C y el MetS en pacientes con T2DM de un distrito de Madrid, España. Pacientes y métodos: Se reclutaron 100 pacientes con T2DM del Hospital Universitario Infanta Leonor (distrito de Vallecas, Madrid). A todos, entre enero de 2014 y junio de 2017, se les determinaron cada 6 meses los diferentes parámetros lipídicos, calculándose los índices ApoB/ApoA1 y no-HDL-C/HDL-C. De cada parámetro se realizó una media de 4-5 determinaciones. Se utilizó la U de Mann-Whitney para las comparaciones entre medias, la correlación de Spearman para las relaciones entre variables y un análisis de regresión multivariable para determinar la asociación entre el MetS y los índices ApoB/ApoA1 y no-HDL-C/HDL-C. Una p < 0,05 fue significativa. Resultados: Se han observado asociaciones entre MetS y ApoA1 (R2 = 0,164; p = 0,028), ApoB/ApoA1 (R2 = 0,187; p = 0,001) y no-HDL-C/HDL-C (R2 = 0,269; p = 0,0001); y en mujeres con MetS, entre ApoB/ApoA1 y cardiomiopatía isquémica (IC) (R2 = 0,160; p = 0,032), que permanecen después de ajustar las comorbilidades y los factores de riesgo. Conclusiones: En los pacientes con T2DM estudiados, el MetS se asocia de forma independiente con ApoA1, ApoB/ApoA1 y con no-HDL-C/HDL-C. Ambos índices son mejores predictores de MetS que sus componentes por separado. El índice ApoB/ApoA1 podría usarse como marcador de riesgo cardiovascular en mujeres con MetS
Subject(s)
Humans , Female , Middle Aged , Aged , Metabolic Syndrome/complications , Diabetes Mellitus, Type 2/complications , Biomarkers/blood , Myocardial Ischemia/diagnosis , Apolipoprotein A-I/blood , Apolipoprotein B-100/blood , Statistics, Nonparametric , Lipoproteins, HDL , Retrospective Studies , Cardiovascular Diseases/epidemiology , Risk FactorsABSTRACT
BACKGROUND AND AIM: Presence of metabolic syndrome (MS) in patients with type 2 diabetes mellitus (T2DM) involves an increased risk of cardiovascular disease and death. Markers such as ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios have been used to predict this risk with conflicting results. The study objective was to establish the relationship between the apoB/apoA1 and non-HDL-cholesterol/HDL-cholesterol ratios and MS in T2DM patients from a Madrid (Spain) district. PATIENTS AND METHODS: One hundred patients with T2DM who attended University Hospital Infanta Leonor (Vallecas, Madrid, Spain) between January 2014 and June 2017 were enrolled. A blood sample was taken every 6 months from all patients to measure the different lipid parameters and to calculate ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. A Mann-Whitney's U test to compare means and a Spearman's correlation test for correlations between variables were used, and a multivariate regression analysis was performed to determine the association between MS and the ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. Values of p<0.05 were considered significant. RESULTS: Associations were found between MS and ApoA1 (R2=0.164, p=0.028), ApoB/ApoA1 (R2=0.187, p=0.001), and non-HDL-cholesterol/HDL-cholesterol (R2= 0.269, p=0.0001) ratios and, in women with MS, between ApoB/ApoA1 ratio and ischemic cardiomyopathy (IC) (R2=0.160, p=0.032). Associations remained after adjusting for comorbidities and risk factors. CONCLUSIONS: In the T2DM patients studied, MS was independently associated to ApoA1 and the ApoB/ApoA1 and non-HDL-cholesterol/HDL-cholesterol ratios. Both ratios were better predictors of MS in T2DM subjects that its components alone. The ApoB/ApoA1 ratio could be used as a cardiovascular risk marker in women with MS.
Subject(s)
Apolipoprotein A-I/blood , Apolipoprotein B-100/blood , Diabetes Mellitus, Type 2/blood , Metabolic Syndrome/blood , Myocardial Ischemia/blood , Age Factors , Aged , Biomarkers/blood , C-Reactive Protein/analysis , Chi-Square Distribution , Cholesterol/blood , Diabetes Mellitus, Type 2/complications , Female , Humans , Male , Metabolic Syndrome/complications , Middle Aged , Regression Analysis , Retrospective Studies , Sex Factors , Statistics, NonparametricABSTRACT
Acute coronary syndrome (ACS) is the leading cause of death in elderly patients worldwide. Due its participation in apoptosis, fibrosis, and angiogenesis, transforming growth factor-ß (TGF-ß) isoforms had been categorized as risk factors for cardiovascular diseases. However, due their contradictory activities, a cardioprotective role has been suggested. The aim was to measure the plasma levels of TGF-ß1, 2, and 3 proteins in patients with ACS. This was a case-control study including 225 subjects. The three activated isoforms were measured in serum using the Bio-Plex Pro TGF-ß assay by means of magnetic beads; the fluorescence intensity of reporter signal was read in a Bio-Plex Magpix instrument. We observed a significant reduction of the three activated isoforms of TGF-ß in patients with ACS. The three TGF-ß isoforms were positively correlated with each other in moderate-to-strong manner. TGFß-2 was inversely correlated with glucose and low-density lipoprotein (LDL)-cholesterol, whereas TGF-ß3 was inversely correlated with the serum cholesterol concentration. The production of TGF-ß1, TGF-ß2, and TGF-ß3 are decreased in the serum of patients with ACS. Further follow-up controlled studies with a larger sample size are needed, in order to test whether TGF-ß isoforms could be useful as biomarkers that complement the diagnosis of ACS.
Subject(s)
Acute Coronary Syndrome/pathology , Transforming Growth Factor beta/blood , Acute Coronary Syndrome/metabolism , Adult , Aged , Biomarkers/blood , Case-Control Studies , Cholesterol/blood , Cholesterol, LDL/blood , Female , Humans , Male , Middle Aged , Protein Isoforms/blood , Protein Isoforms/metabolism , Transforming Growth Factor beta/metabolismABSTRACT
Acute coronary syndrome (ACS) describes any condition characterized by myocardial ischaemia and reduction in blood flow. The physiopathological process of ACS is the atherosclerosis where MIF operates as a major regulator of inflammation. The aim of this study was to assess the mRNA expression of MIF gene and its serum levels in the clinical manifestations of ACS and unrelated individuals age- and sex-matched with patients as the control group (CG). All samples were run using the conditions indicated in TaqMan Gene Expression Assay protocol. Determination of MIF serum levels were performed by enzyme-linked immunosorbent assay and MIF ELISA Kit. ST-segment elevation myocardial infraction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) showed 0.8 and 0.88, respectively, less expression of MIF mRNA with regard to CG. UA and STEMI presented more expression than NSTEMI 5.23 and 0.68, respectively. Otherwise, ACS patients showed significant higher MIF serum levels (p=0.02) compared with CG. Furthermore, the highest soluble levels of MIF were presented by STEMI (11.21 ng/dL), followed by UA (10.34 ng/dL) and finally NSTEMI patients (8.75 ng/dL); however, the differences were not significant. These novel observations further establish the process of MIF release after cardiovascular events and could support the idea of MIF as a new cardiac biomarker in ACS.
ABSTRACT
Antecedentes y objetivo: Las alteraciones en el metabolismo de los lípidos contribuyen al síndrome coronario agudo (SCA). Se ha demostrado que los polimorfismos rs670, rs5070 y rs693 modifican el riesgo de enfermedad cardiovascular. La apolipoproteína A-I (ApoA-I) desempeña un papel principal en el transporte inverso del colesterol; la apolipoproteína B (ApoB) contribuye a la acumulación de colesterol en la placa. El objetivo de este estudio fue investigar la asociación entre los polimorfismos rs670 y rs5070 de APOA1 y el polimorfismo rs693 de APOB con SCA y los niveles circulantes de estas proteínas, e investigar si ApoB/ApoA-I podría introducirse como parámetro independiente predictor de riesgo de la enfermedad cardiovascular y como biomarcador del tratamiento de reducción de lípidos en la población mexicana. Métodos: Se incluyó a 300 pacientes con SCA y 300 sujetos control (SC). Resultados: Ni las frecuencias genotípicas ni las alélicas de los polimorfismos rs670, rs5070 y rs693 reflejaron diferencias estadísticamente significativas entre los grupos. Los niveles séricos de ApoA-I (195 frente a 161,4mg/dl; p<0,001) y ApoB (167 frente a 136,9mg/dl; p<0,001) fueron significativamente superiores en los SC en comparación con los SCA; sin embargo, no existió asociación genética. Los pacientes con angina inestable reflejaron los niveles más elevados de ApoA-I (varones: 176,3mg/dl; mujeres: 209,1mg/dl). Conclusión: Los polimorfismos rs670, rs5070 y rs693 no constituyen factores de susceptibilidad genética para SCA en la población de México y no tienen efecto sobre las concentraciones de sus apolipoproteínas. En nuestra población, ApoA-I, ApoB y c-HDL podrían constituir unos mejores biomarcadores del riesgo cardiovascular, y podrían indicar si las dosis de estatinas reducen debidamente las partículas aterogénicas
Background and objective: Lipid metabolism alterations contribute to acute coronary syndrome (ACS). rs670, rs5070 and rs693 polymorphisms have shown to modify the risk of cardiovascular disease. Apolipoprotein A-I (ApoA-I) plays a major role in reverse cholesterol transport; apolipoprotein B (ApoB) contributes to accumulation of cholesterol in the plaque. The aim of this study was to investigate the association of rs670 and rs5070 polymorphisms of APOA1 and rs693 polymorphism of APOB with ACS and circulating levels of its proteins and find if ApoB/ApoA-I could be implemented as an independent parameter of risk for cardiovascular disease and as a biomarker of lipid-lowering therapy effectiveness in Mexican population. Methods: Three hundred patients with ACS and 300 control subjects (CS) were included. Results: Neither genotype nor allele frequencies of rs670, rs5070 and rs693 polymorphisms showed statistical differences between groups. Serum levels of ApoA-I (195 vs. 161.4mg/dL; P<.001) and ApoB (167 vs. 136.9mg/dL; P<.001) were significantly higher in CS compared with ACS; however, there was no genetic association. Unstable angina patients showed the highest ApoA-I levels (males: 176.3mg/dL; females: 209.1mg/dL). Conclusion: The rs670, rs5070 and rs693 polymorphisms are not genetic susceptibility factors for ACS in Mexican population and had no effect on their apolipoprotein concentrations. In our population, ApoA-I, ApoB and HDL-C could be better biomarkers of cardiovascular risk and could indicate if statins doses reduce atherogenic particles properly
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Acute Coronary Syndrome/complications , Apolipoproteins B , Apolipoprotein A-I , Mexico/epidemiology , Risk Factors , Biomarkers , Lipid Metabolism/physiology , Hyperlipidemias/therapy , Atherosclerosis/physiopathology , Polymorphism, Genetic/physiologyABSTRACT
Introducción y objetivo: Cambios moleculares en el gen CTLA-4 pueden modificar la habilidad para controlar la proliferación de los linfocitos T, y promover la persistencia o eliminación del virus de la hepatitis C (VHC). Nuestro objetivo fue investigar la frecuencia y asociación de los polimorfismos −319 C/T y +49 A/G del gen CTLA-4, en pacientes con infección por VHC. Métodos: Los polimorfismos del gen CTLA-4 (−319 C/T en la región promotora y +49 A/G en el exón 1) fueron analizados por T-ARMS-PCR en 420 individuos, incluidos 205 pacientes con infección crónica por VHC y 215 sujetos sanos. Resultados: Se encontró una asociación positiva del alelo +49G con la infección por VHC (OR 1,48; IC 95% 1,09-2,02; p=0,02), y con el sexo masculino (OR 1,80; IC 95% 1,16-2,79; p=0,02), ambos en enfermedad crónica (sin cirrosis). Se observaron diferencias significativas en la distribución de los genotipos del polimorfismo +49 A/G, entre los pacientes con infección por VHC y los sujetos sanos en un modelo genético dominante (GG+GA frente a AA; OR1,57; IC 95% 1,05-2,33; p=0,04). No se observaron diferencias en las frecuencias del polimorfismo −319 C/T, entre pacientes con VHC y sujetos sanos. El haplotipo -319C/+49G confiere susceptibilidad a la infección por el genotipo 3 del VHC (OR 10,68; IC 95% 1,17-96,97; p=0,04). Conclusiones: El alelo +49G confiere susceptibilidad a infección por VHC y a infección en el sexo masculino, ambos en enfermedad crónica. Además, el haplotipo -319C/+49G confiere susceptibilidad a la infección por el genotipo 3 del VHC. Nuestros resultados evidencian una implicación importante de los polimorfismos −319 C/T y +49 A/G en la infección por VHC
Introduction and objective: Molecular changes in the CTLA-4 gene can modify the ability to control T lymphocyte proliferation, and promote the persistence or elimination of the hepatitis C virus (HCV). We aimed to investigate the frequency and association of -319 C/T and +49 A/G polymorphism in the CTLA-4 gene in patients infected with HCV. Methods: The CTLA-4 gene polymorphisms (-319 C/T in the promoter region, and +49 A/G in exon 1) were analysed by T-ARMS-PCR in 420 individuals, including 205 chronic HCV infected patients and 215 healthy subjects. Results: We found a positive association of +49G allele with HCV infection (OR 1.48; 95% CI 1.09-2.02; p=.02), and with males (OR 1.80; 95% CI 1.16-2.79; p=.02), both in chronic disease (without cirrhosis). Also, significant differences in +49 A/G genotypes distribution between HCV infected patients and healthy subjects were shown in a dominant genetic model (GG+GA versus AA; OR 1.57; 95% CI 1.05-2.33; p=.04). No significant differences were observed in the -319 C/T polymorphism between HCV infected patients and healthy subjects. Moreover, -319C/+49G haplotype confers susceptibility to HCV genotype 3 infection (OR 10.68; 95% CI 1.17-96.97; p=.04). Conclusions: The +49G allele confers susceptibility to HCV infection and with male gender, both in chronic disease. In addition, the −319C/+49G haplotype confers susceptibility to HCV genotype 3 infection. Our results support an important role of the −319 C/T and +49 A/G polymorphisms in HCV infection
Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Hepacivirus/pathogenicity , Hepatitis C, Chronic/genetics , CTLA-4 Antigen/genetics , Polymorphism, Genetic/genetics , Genetic Predisposition to Disease/genetics , Genetic Testing/methods , Case-Control Studies , Haplotypes/genetics , Cross-Sectional StudiesABSTRACT
BACKGROUND AND OBJECTIVE: Lipid metabolism alterations contribute to acute coronary syndrome (ACS). rs670, rs5070 and rs693 polymorphisms have shown to modify the risk of cardiovascular disease. Apolipoprotein A-I (ApoA-I) plays a major role in reverse cholesterol transport; apolipoprotein B (ApoB) contributes to accumulation of cholesterol in the plaque. The aim of this study was to investigate the association of rs670 and rs5070 polymorphisms of APOA1 and rs693 polymorphism of APOB with ACS and circulating levels of its proteins and find if ApoB/ApoA-I could be implemented as an independent parameter of risk for cardiovascular disease and as a biomarker of lipid-lowering therapy effectiveness in Mexican population. METHODS: Three hundred patients with ACS and 300 control subjects (CS) were included. RESULTS: Neither genotype nor allele frequencies of rs670, rs5070 and rs693 polymorphisms showed statistical differences between groups. Serum levels of ApoA-I (195 vs. 161.4mg/dL; P<.001) and ApoB (167 vs. 136.9mg/dL; P<.001) were significantly higher in CS compared with ACS; however, there was no genetic association. Unstable angina patients showed the highest ApoA-I levels (males: 176.3mg/dL; females: 209.1mg/dL). CONCLUSION: The rs670, rs5070 and rs693 polymorphisms are not genetic susceptibility factors for ACS in Mexican population and had no effect on their apolipoprotein concentrations. In our population, ApoA-I, ApoB and HDL-C could be better biomarkers of cardiovascular risk and could indicate if statins doses reduce atherogenic particles properly.
Subject(s)
Acute Coronary Syndrome/genetics , Apolipoprotein A-I/genetics , Apolipoprotein B-100/genetics , Polymorphism, Single Nucleotide , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/drug therapy , Aged , Aged, 80 and over , Apolipoprotein A-I/blood , Apolipoprotein B-100/blood , Biomarkers/blood , Case-Control Studies , Cross-Sectional Studies , Female , Gene Frequency , Genetic Markers , Genetic Predisposition to Disease , Genotype , Humans , Hypolipidemic Agents/therapeutic use , Male , Mexico , Middle Aged , Risk Factors , Treatment OutcomeABSTRACT
INTRODUCTION AND OBJECTIVE: Molecular changes in the CTLA-4 gene can modify the ability to control T lymphocyte proliferation, and promote the persistence or elimination of the hepatitis C virus (HCV). We aimed to investigate the frequency and association of -319 C/T and +49 A/G polymorphism in the CTLA-4 gene in patients infected with HCV. METHODS: The CTLA-4 gene polymorphisms (-319 C/T in the promoter region, and +49 A/G in exon 1) were analysed by T-ARMS-PCR in 420 individuals, including 205 chronic HCV infected patients and 215 healthy subjects. RESULTS: We found a positive association of +49G allele with HCV infection (OR 1.48; 95% CI 1.09-2.02; p=.02), and with males (OR 1.80; 95% CI 1.16-2.79; p=.02), both in chronic disease (without cirrhosis). Also, significant differences in +49 A/G genotypes distribution between HCV infected patients and healthy subjects were shown in a dominant genetic model (GG+GA versus AA; OR 1.57; 95% CI 1.05-2.33; p=.04). No significant differences were observed in the -319 C/T polymorphism between HCV infected patients and healthy subjects. Moreover, -319C/+49G haplotype confers susceptibility to HCV genotype 3 infection (OR 10.68; 95% CI 1.17-96.97; p=.04). CONCLUSIONS: The +49G allele confers susceptibility to HCV infection and with male gender, both in chronic disease. In addition, the -319C/+49G haplotype confers susceptibility to HCV genotype 3 infection. Our results support an important role of the -319 C/T and +49 A/G polymorphisms in HCV infection.
Subject(s)
CTLA-4 Antigen/genetics , Hepatitis C, Chronic/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that plays a crucial role as a regulator of the innate and adaptive immune responses and takes part in the destructive process of the joint in rheumatoid arthritis (RA) by promoting angiogenesis and inducing proinflammatory cytokines and matrix metalloproteinases (MMP). We evaluated if recombinant human MIF (rhMIF) induces the production of TNF-α, IFN-γ, IL-1ß, IL-6, IL-10, IL-17A, and IL- 17F in peripheral blood mononuclear cells (PBMC) from RA patients and control subjects (CS). METHODS: The PBMC from RA patients and CS were stimulated for 24 hours with combinations of LPS, rhMIF or the MIF antagonist ISO-1. Cytokine profiles were measured using a multiplex immunoassay and, macrophage migration inhibitory factor (MIF) was determined by ELISA kit. RESULTS: The PBMC of CS and RA produced Th1 and Th17 cytokines under stimulation with rhMIF, however, this effect was higher in the cells of RA patients. The rhMIFstimulated PBMC from RA patients produced higher levels of Th1 and Th17 cytokines in comparison with unstimulated cells: TNF-α (538.81 vs. 5.02 pg/mL, p<0.001), IFN-γ (721.90 vs. 8.40 pg/mL, p<0.001), IL-1ß (150.14 vs. 5.17 pg/mL, p<0.05), IL-6 (19769.70 vs. 119.85 pg/mL, p<0.001), IL-17A (34.97 vs. 0.90 pg/mL, p<0.01) and IL-17F (158.43 vs. 0.92 pg/mL, p<0.001). CONCLUSION: These results highlight the potential role of MIF in the establishment of the chronic inflammatory process in RA via Th1 and Th17 cytokine profile induction and provide new evidence of the role of MIF to stimulate the IL-17A and IL-17F expression in PBMC from RA and CS.