Influence of Genetic Admixture Components on CYP3A5*3 Allele-Associated Hypertension in Amerindian Populations From Northwest Mexico

CYP3A5 metabolizes endogenous substrates and ~30% of prescription drugs. The CYP3A5 gene contains an active CYP3A5*1 allele, and a non-functional version, the CYP3A5*3 (rs776746), with consequences for drug therapeutic responses and side effects. Both CYP3A5*1 and *3 have been associated with hypertension. The frequency of CYP3A5*3 varies between populations of different ancestries, with Europeans having the highest allele frequency (> 90%). Given the importance of CYP3A5*3 in drug response and hypertension development, the aim of the present study was to evaluate the frequency of this polymorphism and its association with hypertension in vulnerable indigenous populations in Mexico. A total of 372 subjects were recruited from eight ethnic groups in Northwest Mexico. Systolic (SBP), diastolic (DBP), and median (MBP) blood pressures as well as body mass index (BMI) were measured. Ancestry was evaluated through STR analysis, and the CYP3A5*1/*3 polymorphisms were identified using real-time PCR with TaqMan® probes. Higher frequencies of CYP3A5*1 and *3 were observed in groups with higher (>90%) and lower (<90%) Amerindian ancestry, respectively. The CYP3A5*3/*3 genotype was more frequent in indigenous women with higher SBP and DBP values. On the other hand, the *1 allele showed a protective effect against both high SBP (OR, 0.38; 95% CI, 0.17–0.83, p = 0.001) and DBP (OR 0.38, 95% CI 0.18–0.81, p = 0.007) in women. This association remained significant after adjusting for BMI and age for diastolic (OR, 0.38; 95% CI, 0.17–0.84, p = 0.011) and systolic BP (OR, 0.33; 95% CI, 0.15–0.76, p = 0.005) BP levels in women. Thus, the frequency of CYP3A5*3 varies between groups and seems to depend on ancestry, and CYP3A5*1 decreases the risk of hypertension in Mexican indigenous women. This population analysis of CYP3A5*1/*3 has profound implications not only for the susceptibility to diseases, such as hypertension, but also for safer drug administration regimens, assuring better therapeutic responses and fewer side effects

Identificación de Marcadores Genéticos Asociados a un Desenlace Desfavorable en Pacientes con Peritonitis Secundaria no Apendicular con y sin Trastornos de la Nutrición

OBJETIVO: Determinar si los polimorfismos G-2548A del gen LEP, A223G del gen LEPR y C34G del gen PPARg, son factores genéticos de riesgo para un desenlace desfavorable en peritonitis secundaria. MATERIAL Y MÉTODOS: Cohorte prospectiva. Se incluyeron 75 pacientes del servicio de cirugía general del Hospital general de Durango, SSA. Con diagnóstico de peritonitis secundaria no apendicular, confirmada quirúrgicamente. Se excluyeron pacientes con peritonitis apendicular, pacientes con peritonitis pancreática, o con tratamiento inmunosupresor o con ingesta crónica de corticoesteriodes. Se realizó extracción de ADN a partir de sangre total, mediante el método DTAB/CTAB, reacción en cadena de la polimerasa punto final y mutación especifica, así como polimorfismos de longitud de fragmentos de restricción. RESULTADOS. Se captaron 75 pacientes (42 ♂ Ds±19.5 y 33♀ Ds±20.25), la edad promedio del grupo de hombres sobrevivientes fue de 43 y para las mujeres de 55 años respectivamente. Un IMC (24.20♀ y 23.6♂). De los 75 pacientes, 22 fallecieron, y 53 sobrevivieron. Realizando el análisis de riesgos mediante el modelo de razón de momios, se observa que el alelo mutado A del polimorfismo G-2548A del gen LEP representa 4.64 veces más riesgo de no sobrevida con respecto a los individuos que presentan el alelo silvestre (G). Con respecto al polimorfismo A223G del gen LEPR, la presencia del alelo mutado (G), sugiere la posibilidad de un factor protector 3.5 veces, sin embargo el intervalo de confianza no es definitorio. El polimorfismo C34G del gen PPARg no representa un factor de riesgo para desenlace desfavorabl

Preeclampsia association of placental nucleotide variations in eNOS, VEGFA, and FLT-1 genes in Latin American pregnant women

Q2Q1Mujeres con preeclampsiaIntroduction: Preeclampsia is a leading cause of maternal and fetal morbidity in low- and middle-income countries, including those in Latin America. Placental vascular alterations are crucial in the pathophysiology of preeclampsia and few studies have evaluated nucleotide variations on genes associated with vascular regulation in the human placenta. This study aimed to evaluate whether placental nucleotide variations on eNOS, VEGFA, and FLT-1 genes are more frequently associated with preeclampsia in the Latin American population. Methods: This case-control study included placental tissue from 88 controls and 82 cases that were genotyped through Taqman probes for eNOS, VEGFA, and FLT-1 genes. The intergroup comparisons were analyzed with the Mann-Whitney U test. Genotype and allele frequencies were compared by the X2 test. The association between the nucleotide variants with preeclampsia was evaluated through logistic regression analysis. Results: A significant association was observed for VEGFA SNV rs2010963 (OR 1.95; CI 95% 1.13–3.37), after adjusting for population substructure. The allele combination T, G, G, C, C, C (rs2070744, rs1799983, rs2010963, rs3025039, rs699947 and rs4769613 respectively), showed a negative association with preeclampsia (OR 0.08; CI 95% 0.01–0.93). results. Discussion: Placental SNV rs2010963 in the VEGFA gene was a risk factor for preeclampsia, while the allele combination T, G, G, C, C, C may represent potential protective factors for preeclampsia within Latin American women.https://orcid.org/0000-0002-6804-0979https://orcid.org/0000-0002-0141-1149Revista Internacional - IndexadaA1N

Preeclampsia association of placental nucleotide variations in eNOS, VEGFA, and FLT-1 genes in Latin American pregnant women

Introduction: Preeclampsia is a leading cause of maternal and fetal morbidity in low- and middle-income countries, including those in Latin America. Placental vascular alterations are crucial in the pathophysiology of preeclampsia and few studies have evaluated nucleotide variations on genes associated with vascular regulation in the human placenta. This study aimed to evaluate whether placental nucleotide variations on eNOS, VEGFA, and FLT-1 genes are more frequently associated with preeclampsia in the Latin American population. Methods: This case-control study included placental tissue from 88 controls and 82 cases that were genotyped through Taqman probes for eNOS, VEGFA, and FLT-1 genes. The intergroup comparisons were analyzed with the Mann-Whitney U test. Genotype and allele frequencies were compared by the X2 test. The association between the nucleotide variants with preeclampsia was evaluated through logistic regression analysis. Results: A significant association was observed for VEGFA SNV rs2010963 (OR 1.95; CI 95% 1.13–3.37), after adjusting for population substructure. The allele combination T, G, G, C, C, C (rs2070744, rs1799983, rs2010963, rs3025039, rs699947 and rs4769613 respectively), showed a negative association with preeclampsia (OR 0.08; CI 95% 0.01–0.93). results. Discussion: Placental SNV rs2010963 in the VEGFA gene was a risk factor for preeclampsia, while the allele combination T, G, G, C, C, C may represent potential protective factors for preeclampsia within Latin American women.Fil: Macías Salas, Alejo. INSTITUTO POLITÉCNICO NACIONAL (IPN);Fil: Sosa Macías, Martha. INSTITUTO POLITÉCNICO NACIONAL (IPN);Fil: Barragán Zúñiga, Laura Jazel. INSTITUTO POLITÉCNICO NACIONAL (IPN);Fil: Blanco Castañeda, Ricardo. INSTITUTO POLITÉCNICO NACIONAL (IPN);Fil: Damiano, Alicia Ermelinda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Garcia Robles, Reggie. Pontificia Universidad Javeriana; ColombiaFil: Ayala Ramírez, Paola. Pontificia Universidad Javeriana; ColombiaFil: Bueno Sánchez, Julio. Universidad de Antioquia; ColombiaFil: Giachini, Fernanda Regina. Universidade Federal do Mato Grosso do Sul; BrasilFil: Escudero, Carlos. Universidad del Bio Bio; ChileFil: Galaviz Hernández, Carlos. INSTITUTO POLITÉCNICO NACIONAL (IPN)

The Synergistic Effect of Quince Fruit and Probiotics (<i>Lactobacillus</i> and <i>Bifidobacterium</i>) on Reducing Oxidative Stress and Inflammation at the Intestinal Level and Improving Athletic Performance during Endurance Exercise

Endurance exercise promotes damage at the intestinal level and generates a variety of symptoms related to oxidative stress processes, inflammatory processes, microbiota dysbiosis, and intestinal barrier damage. This study evaluated the effects of quince (Cydonia oblonga Mill.) and probiotics of the genera Lactobacillus and Bifidobacterium on intestinal protection and exercise endurance in an animal swimming model. Phytochemical characterization of the quince fruit demonstrated a total dietary fiber concentration of 0.820 ± 0.70 g/100 g and a fiber-bound phenolic content of 30,218 ± 104 µg/g in the freeze-dried fruit. UPLC-PDA-ESI-QqQ analyses identified a high content of polyphenol, mainly flavanols, hydroxycinnamic acids, hydroxybenzoic acids, flavonols, and, to a lesser extent, dihydrochalcones. The animal model of swimming was performed using C57BL/6 mice. The histological results determined that the consumption of the synbiotic generated intestinal protection and increased antioxidant (catalase and glutathione peroxidase enzymes) and anti-inflammatory (TNF-α and IL-6 and increasing IL-10) activities. An immunohistochemical analysis indicated mitochondrial biogenesis (Tom2) at the muscular level related to the increased swimming performance. These effects correlated mainly with the polyphenol content of the fruit and the effect of the probiotics. Therefore, this combination of quince and probiotics could be an alternative for the generation of a synbiotic product that improves exercise endurance and reduces the effects generated by the practice of high performance sports