The Genetic Variants -717T>C (rs2794521), 1444G>A (rs1130864), and 1846 C > T (rs1205) of CRP Gene, Their Haplotypes, and Their Association with Serum CRP Levels, Acute Coronary Syndrome, and Diabetes in Patients from Western Mexico.

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.

ApoB/ApoA1 ratio and non-HDL-cholesterol/HDL-cholesterol ratio are associated to metabolic syndrome in patients with type 2 diabetes mellitus subjects and to ischemic cardiomyopathy in diabetic women / Los índices ApoB/ApoA1 y no-HDL-colesterol/HDL-colesterol se asocian con el síndrome metabólico en sujetos con diabetes mellitus tipo 2 y con cardiomiopatía en mujeres diabéticas

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

ApoB/ApoA1 ratio and non-HDL-cholesterol/HDL-cholesterol ratio are associated to metabolic syndrome in patients with type 2 diabetes mellitus subjects and to ischemic cardiomyopathy in diabetic women.

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.

Polimorfismos de los genes APOA1 y APOB y concentraciones de sus apolipoproteínas como biomarcadores de riesgo en el síndrome coronario agudo: relación con la efectividad del tratamiento hipolipemiante / APOA1 and APOB polymorphisms and apolipoprotein concentrations as biomarkers of risk in acute coronary syndrome: Relationship with lipid-lowering therapy effectiveness

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

APOA1 and APOB polymorphisms and apolipoprotein concentrations as biomarkers of risk in acute coronary syndrome: Relationship with lipid-lowering therapy effectiveness. / Polimorfismos de los genes APOA1 y APOB y concentraciones de sus apolipoproteínas como biomarcadores de riesgo en el síndrome coronario agudo: relación con la efectividad del tratamiento hipolipemiante.

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.

Relationship Between C-Reactive Protein Serum Concentration and the 1846 C>T (rs1205) Polymorphism in Patients with Acute Coronary Syndrome from Western Mexico.

AIM: To determine the relationship among the 1846 C>T (rs1205) polymorphism, C-reactive protein (CRP) concentration, and interleukin 6 (IL-6) serum levels in patients with acute coronary syndrome (ACS) from Western Mexico. METHODS: Three hundred participants in the control group (CG) and 300 patients with ACS from Western Mexico were included in the study. Genotyping was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). High-sensitivity CRP (hs-CRP) concentration was measured by immunonephelometry. For IL-6 measurement, we used a solid-phase sandwich Enzyme-Linked Immunosorbent Assay. RESULTS: Serum CRP concentration was increased in patients compared with controls (19 mg/L vs. 2.00 mg/L; p < 0.0001). ST-segment elevation myocardial infarction exhibited a higher CRP concentration than without elevation (non-ST-segment elevation myocardial infarction) and patients with unstable angina (21.81, 17.10, and 5.91 mg/L; p < 0.01). The rs1205 CRP polymorphism was not associated with ACS; however, T carriers had lower CRP concentrations than C/C (2.80 mg/L vs. 5.20 mg/L; p = 0.004) in CG and ACS (17.76 vs. 21.45; p = 0.046). IL-6 showed a strong positive correlation with CRP concentration in ACS patients (rho = 0.74, p < 0.0001). CONCLUSIONS: Patients with ACS had increased CRP levels compared with CG, and this appears to be related with ACS clinical spectrum severity. The rs1205 polymorphism is not a susceptibility genetic marker to ACS in Western Mexico population; however, the T allele is associated with lower CRP concentration. Further studies are needed to confirm the prognostic value of ACS and IL-6/CRP correlation, but it could be a reliable test for predicting adverse cardiac events in the Mexican population.

Life-long consequences of postnatal normoxia exposure in rats raised at high altitude.

We tested the hypothesis that exposure of high-altitude (HA) rats to a period of postnatal normoxia has long-term consequences on the ventilatory and hematological acclimatization in adults. Male and female HA rats (3,600 m, Po(2) ≃ 100 Torr; La Paz, Bolivia) were exposed to normal room air [HA control (HACont)] or enriched oxygen (32% O(2); Po(2) ≃ 160 Torr) from 1 day before to 15 days after birth [HA postnatal normoxia (HApNorm)]. Hematocrit and hemoglobin values were assessed at 2, 12, and 32 wk of age. Cardiac and lung morphology were assessed at 12 wk by measuring right ventricular hypertrophy (pulmonary hypertension index) and lung air space-to-tissue ratio (indicative of alveolarization). Respiratory parameters under baseline conditions and in response to 32% O(2) for 10 min (relieving the ambient hypoxic stimulus) were measured by whole body plethysmography at 12 wk. Finally, we performed a survival analysis up to 600 days of age. Compared with HACont, HApNorm rats had reduced hematocrit and hemoglobin levels at all ages (both sexes); reduced right ventricular hypertrophy (both sexes); lower air space-to-tissue ratio in the lungs (males only); reduced CO(2) production rate, but higher oxygen uptake (males only); and similar respiratory frequency, tidal volume, and minute ventilation. When breathing 32% O(2), HApNorm male rats had a stronger decrease of minute ventilation than HACont. HApNorm rats had a marked tendency toward longer survival throughout the study. We conclude that exposure to ambient hypoxia during postnatal development in HA rats has deleterious consequences on acclimatization to hypoxia as adults.

Enhanced erythropoietin expression in the brainstem of newborn rats at high altitude.

In addition to its role in elevating red blood cell number, erythropoietin (Epo) exerts protective functions against acute and delayed degenerative diseases of the brain. Moreover, we have recently demonstrated that endogenously synthesized Epo and soluble Epo receptor (a negative regulator of Epo binding to the Epo receptor) in the central nervous system play a crucial role in facilitating the ventilatory response and acclimatization to hypoxia. Here we hypothesized that cerebral Epo in the brainstem is implicated in the process that allows cardiorespiratory acclimatization to high altitude hypoxia during the postnatal period. Thus, we evaluated the postnatal ontogeny of cerebral Epo concentration of Sprague-Dawley rats living and reproducing at high altitude for longer than 19 years (3600 m in La Paz, Bolivia). Our results show that postnatal Epo concentration in high-altitude rats is higher in the brainstem than in the forebrain. Moreover, although Epo concentration in the forebrain of high-altitude rats is similar to sea-level controls, Epo level in the brainstem is surprisingly 2-fold higher in high-altitude rats than in sea-level controls. These findings strongly suggest that brainstem Epo plays an important role in tolerance to high altitude hypoxia after birth. From a clinical perspective, a better understanding of the role of Epo in the postnatal development of cardiorespiratory responses in neonates exposed to acute or chronic hypoxia might be useful.