Efectos de un entrenamiento de miembro inferior con restricción parcial del flujo sanguíneo en la fuerza muscular y biomarcadores sistémicos de daño muscular e inflamación / Effects of lower limb training with partial restriction of blood flow on muscle strength and systemic biomarkers of muscle damage and inflammation

El entrenamiento de fuerza, especialmente con alta intensidad de carga, permite aumentar la fuerza y trofismo muscular, pero también se asocia a daño muscular inducido por ejercicio (DMIE). Una nueva modalidad de entrenamiento, combina una baja intensidad de carga con la restricción parcial del flujo sanguíneo (RPFS) alrededor del músculo, siendo prometedor en cuanto el desarrollo de la fuerza y trofismo muscular. El objetivo del estudio fue comparar el rendimiento de fuerza máxima de los músculos cuádriceps e isquiotibiales (FM-Q y FM-I) y marcadores de daño muscular (CK) e inflamación sistémica (PCRus) entre un entrenamiento de baja intensidad de carga con RPFS, versus uno de alta y otro de baja intensidad de carga sin RPFS en jóvenes físicamente activos durante cuatro semanas de entrenamiento. Veintitrés participantes midieron la FM-Q y FM-I previo y al término de la intervención; además, antes del inicio de la primera sesión, y antes y después del término de la última sesión se midió la CK y PCRus. En los tres tipos de entrenamiento se produjeron aumentos equivalentes en la fuerza máxima, a excepción de la FM-Q del entrenamiento con baja intensidad sin RPFS. Solo en el entrenamiento con RPFS la CK y PCRus se modifican al finalizar la intervención, y aun cuando el estrés miocelular parece ser más alto que en los otros tipos de entrenamiento, no indicaría daño muscular.

Strength training, especially with high load intensity, allows increasing muscle strength and trophism, but it is also associated with exercise-induced muscle damage (EIMD). A new training modality, a combination of loading with the partial restriction blood flow (PRBF) around the muscle, being promising in the development of strength and muscular trophism. The aim of the study was to compare the maximum strength (MS) performance of quadriceps and hamstrings (MS-Q and MS-I) and muscle damage biomarkers (Creatine Kinase, CK) and systemic inflammation (high sensitivity - CRP, hs-CRP) between a low intensity load training with PRBF, versus one high and another low load intensity without PRBF in physically active youngsters during four weeks of training. Twenty-three participants measured MSQ and MS-I and the intervention term. In addition, before the start of the first session, before and after the end of the last session, CK and hsCRP were measured. In the three types of training the equivalent benefits in MS are produced, an exception of the MS-Q of low intensity training without PRBF. Only in the training with PRBF, the CK and hsCPR are modified at the end of the intervention, and even though the myocellular stress seems to be higher than in the other types of training, it would not indicate muscle damage.

SLCO1B1 c.388A>G Polymorphism Is Associated with HDL-C Levels in Response to Atorvastatin in Chilean Individuals.

The use of statins as the preferred lipid-lowering therapy has clearly demonstrated its efficacy in the treatment of hypercholesterolemia, reducing also the risk of coronary events and cardiovascular disease mortality. In this study, we assessed single nucleotide polymorphisms (SNPs) in the SLCO1B1 gene and their effect on atorvastatin response. We included 129 Chilean hypercholesterolemic patients undergoing 10 mg/day of atorvastatin therapy during 4 weeks. Lipid profile was determined before and after drug administration. Genotyping of SLCO1B1 rs4149056 (c.521T>C) SNP was performed with allele-specific polymerase chain reaction, whilst polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the SLCO1B1 rs2306283 (c.388A>G) variant. After statin therapy, concentrations of TC, LDL-C and TG had a decrease from baseline (p < 0.05). Also, HDL-C levels increased (p < 0.05). Minor allele frequencies for the rs2306283 and rs4149056 variants were 0.547 and 0.136, respectively. LDL-C response to atorvastatin was not associated with the SLCO1B1 rs4149056 nor the rs2306283 polymorphisms (p > 0.05). However, the latter SNP was associated with HDL-C variability after atorvastatin medication (p = 0.02). This study indicates that LDL-C reduction following atorvastatin therapy is not influenced by the SNPs evaluated. In addition, the polymorphism rs2306283 at the SLCO1B1 gene determines greater HDL-C concentrations in response to atorvastatin medication in Chilean hypercholesterolemic subjects.

APOE polymorphisms contribute to reduced atorvastatin response in Chilean Amerindian subjects.

Genetic factors can determine the high variability observed in response to lipid-lowering therapy with statins. Nonetheless, the frequency of single nucleotide polymorphisms (SNPs) and their impact can vary due to ethnicity. Because the Chilean population carries a strong Amerindian background, the objective of this study was to evaluate the influence of apolipoprotein E (APOE) variants (rs429358, rs7412) and the 1959C>T SNP (rs5925) in the low-density lipoprotein receptor (LDLR) in response to atorvastatin treatment in hypercholesterolemic individuals. A hundred and thirty nine subjects undergoing statin therapy were included. Identification of Amerindian mtDNA haplogroups was determined by polymerase chain reaction (PCR) and PCR followed by restriction fragment length polymorphism (RFLP), respectively. SNPs were determined by PCR-RFLP. Out of the 139 individuals studied, 84.4% had an Amerindian background, according to mtDNA analysis. In relation to APOE variants, carriers of the E3/4 genotype presented lower cholesterol reduction compared to genotype E3/3 (LDL-C: -18% vs. -29%, p ˂ 0.001). On the other hand, the LDLR rs5925 SNP was not related to atorvastatin response (p = 0.5760). Our results suggest that APOE SNPs are potential predictors to atorvastatin therapy in Amerindian Chilean subjects.

Influence of SREBP-2 and SCAP gene polymorphisms on lipid-lowering response to atorvastatin in a cohort of Chilean subjects with Amerindian background.

BACKGROUND AND OBJECTIVES: This study evaluated the influence of the polymorphisms G1784C (rs4822063) and A2386G (rs12487736) of SREBP-2 and SCAP genes, respectively, on the response to atorvastatin treatment in a cohort of Chilean subjects with Amerindian background. METHODS: A total of 142 hypercholesterolemic individuals underwent atorvastatin therapy (10 mg/day/1 month). Serum lipids levels before and after treatment were measured. Genotyping of the studied polymorphisms and ethnic characterization through Amerindian haplogroups (A, B, C, and D) of mitochondrial DNA was achieved by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. RESULTS: Of all individuals, 85 % turned out to be Amerindian. C allele carriers for polymorphism G1784C, had a lower total cholesterol reduction (p = 0.015) and low-density lipoprotein cholesterol (LDL-C) (p = 0.013). No differences were found for the A2386G variant. However, those who carried both polymorphisms had a lower LDL-C reduction than carriers of just one of the variants (p = 0.030). CONCLUSION: The G1784C polymorphism of SREBP-2 gene affects atorvastatin response in Chilean subjects with Amerindian background, and may be an important marker for predicting efficacy of lipid-lowering therapy.

FTO gene is related to obesity in Chilean Amerindian children and impairs HOMA-IR in prepubertal girls.

OBJECTIVE: The objective of this study was to investigate the allelic frequency of the fat mass and obesity-associated (FTO) gene (rs9939609) and its influences on obesity and metabolic risk biomarkers in a cohort of normal weight and obese Chilean children determining its ethnicity. METHODS: A total of 136 normal weight children and 238 obese children (between 6 and 11 yr old) from an urban setting were recruited for this case-control study. The children were classified as normal weight [body mass index (BMI) ≥ 5th and < 85th percentiles] or obese (BMI >95th percentile), according to the international age- and gender-specific percentiles defined by the Center for Disease Control and Prevention. The analysis of serum markers was carried out using commercial kits. The FTO polymorphism was determined through a high-resolution melting enabled real time polymerase chain reaction. Ethnicity was determined by analyzing mitochondrial DNA by the restriction fragment length polymorphism method. RESULTS: As much as 85% of the cohort was Amerindian. The minor A allele of rs9939609 was associated with obesity (odds ratio (OR): 1.422 [95% confidence interval (CI) 1.068-1.868] p = 0.015), calculated using an additive model. In sex-stratified analysis we found that the risk variant (A) of rs9939609 was associated with a higher homeostasis model of assessment for insulin (HOMA-IR) in prepubertal obese girls. In male carriers of the A allele, HOMA-IR showed no further deterioration than that already associated with obesity. CONCLUSIONS: In summary, we confirm the association of the FTO gene single-nucleotide polymorphism rs9939609 with obesity in Chilean Amerindian children. Furthermore we show an association between the risk allele (A) and insulin resistance-related markers in prepubertal obese girls.

Asociación de niveles de lípidos y haplogrupos Amerindios de DNA mitocondrial en individuos chilenos hipercolesterolémicos tratados con atorvastatina / Association of serum lipid levels and mitochondrial DNA Amerindian haplogroups in hypercholesterolemic subjects receiving atorvastatin

Resumen: Introducción: La respuesta terapéutica a estatuías se ve influenciada por factores como la edad, género y etnicidad. Con respecto a esto, el background genético de la población chilena es predominantemente Amerindio, definido por la presencia de haplogrupos Amerindios A, B, C y D de DNA mitocondrial (mtDNA). Así, el objetivo del estudio fue evaluar la potencial asociación entre la presencia de haplogrupos Amerindios de mtDNA y niveles de lípidos en individuos chilenos hipercolesterolémicos tratados con Atorvastatina. Métodos: Un total de 42 individuos en dos centros de salud del sur de Chile fueron incluidos en el estudio. En el grupo de pacientes se evaluó la presencia de haplogrupos Amerindios de mtDNA por PCR-RFLP, además de la cuantificación de Colesterol Total, Triglicéridos, Colesterol-HDL y Colesterol-LDL, antes y después del tratamiento con Atorvastatina (10 mg/día). Resultados: El 88.1 por ciento de los sujetos presentó algún haplogrupo Amerindio, no observándose diferencias en los niveles de lípidos pre- tratamiento de acuerdo al haplogrupo. Interesantemente, individuos de haplogrupo B presentaron niveles mayores de Colesterol Total (B: 254 +/- 30 mg/dl v/s C: 213 +/- 48 mg/dl, D: 230 +/- 50 mg/dl; p= 0.0319) y Colesterol-LDL (B: 157 +/- 34 mg/dl v/s C: 118 +/- 45 mg/dl, D: 135 +/- 42 mg/dl; p=0.0344) post-tratamiento. Conclusiones: El haplogrupo B se asocia a niveles mayores de lípidos post-tratamiento en pacientes tratados con Atorvastatina. Estos hallazgos sugieren por primera vez, que la presencia de haplogrupo B de mtDNA determinaría una menor respuesta al tratamiento con Atorvastatina en individuos chilenos con background genético amerindio.

Background: Therapeutic response to statins is influenced by age, gender and ethnicity. The genetic background of the Chilean population is predominantly Amerindian, defined by the presence of mitochondrial DNA (mtDNA) Amerindian haplogroups A, B, C and D Amerindian haplogroups and serum lipid levéis in hypercholesterolemic Chilean subjects receiving atorvastatin Methods: 42 subjects from southern Chile were included. The presence of mtDNA Amerindian haplogroups was evaluated by PCR-RFLP; in addition, total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol were measured before and after treatment with atorvastatin 10 mg/day. Aim: to evaluate a possible association of mtDNA. Ameridian haplogroups and serum lipid levels in hypercholesterolemic Chilean subjects receiving atorvastatin. Result: 88.1 percent of subjects exhibited some Amerindian haplogroup. No relation of lipid levels with haplogroups was observed before treatment. Interestingly, haplogroup B individuals had higher levels of total cholesterol compared to other haplogroups after treatment (haplogroup B : 254 +/- 30 mg/dl; C : 213 +/- 48 mg/dl; D : 230 +/- 50 mg/dl, p=0.0319). Corresponding levels for LDL-cholesterol after treatment in the three groups were 157 +/- 34,118 +/-45 and 135 +/-42 mg/ di, respectively, p=0.0344. Conclusion: Compared to other haplogroups, haplogroup B is associated to higher levels of lipids after treatment with atorvastatin. For the first time, these findings suggest that the presence of mtDNA haplogroup B determines a dimished response to atorvastatin in Chilean subjets with an Amerindian genetic background.