RESUMEN
BACKGROUND: The perinatal environment has a role in the establishment of altered metabolic and inflammatory responses, and could be modulated by microRNAs regulating immune and metabolic processes. OBJECTIVE: To analyze the expression profile of four circulating microRNAs and cytokine serum concentrations in neonates born to overweight and obese women. METHODS: Pregnant women were included and grouped by pregestational body mass index (21 with normal weight, 10 overweight and 10 obese women). A peripheral blood sample was obtained from newborn infants and used to determine circulating miRNAs expression and cytokine serum concentrations. RESULTS: There were significant differences in the expression of three microRNAs between newborns of pregestational obese women and newborns from pregestational normal weight women: miR-155 (p = 0.03), miR-181a (p = 0.02) and miR-221 (p = 0.04). A significant reduction in IL-1ß (p = 0.005) expression was also found in newborns of overweight women; although this cytokine was also diminished in newborns of obese women, this was not statistically significant. An association between IL-1ß concentrations and miR-146a and miR-221 expression was also observed. CONCLUSIONS: Expression of miR-155, miR-181a and miR-221 differs in infants born to obese women compared with infants born to normal weight women. Changes in microRNA expression could participate in the epigenetic foetal programming of metabolic disorders in children born to obese women.
Asunto(s)
MicroARN Circulante/metabolismo , Citocinas/sangre , Obesidad/sangre , Sobrepeso/sangre , Adolescente , Adulto , Índice de Masa Corporal , Femenino , Desarrollo Fetal/genética , Humanos , Recién Nacido , Madres , Embarazo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transcriptoma , Adulto JovenRESUMEN
Many genetic studies have found an association between interferon regulatory factors (IRF) single nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE); however, specific dendritic cell (DC) alterations have not been assessed. The aim of the present study was to address the expression of IRF3 and IRF5 on different DC subsets from SLE patients, as well as their association with interferon (IFN)-α production and novel SNPs. For the genetic association analyses, 156 SLE patients and 272 healthy controls from the Mexican mestizo population were included. From these, 36 patients and 36 controls were included for functional analysis. Two IRF3 SNPs - rs2304206 and rs2304204 - were determined. We found an increased percentage of circulating pDC in SLE patients in comparison to controls (8.04 ± 1.48 versus 3.35 ± 0.8, P = 0.032). We also observed enhanced expression of IRF3 (64 ± 6.36 versus 36.1 ± 5.57, P = 0.004) and IRF5 (40 ± 5.25 versus 22.5 ± 2.6%, P = 0.010) restricted to this circulating pDC subset from SLE patients versus healthy controls. This finding was associated with higher IFN-α serum levels in SLE (160.2 ± 21 versus 106.1 ± 14 pg/ml, P = 0.036). Moreover, the IRF3 rs2304206 polymorphism was associated with increased susceptibility to SLE [odds ratio (OR), 95% confidence interval (CI) = 2.401 (1.187-4.858), P = 0.021] as well as enhanced levels of serum type I IFN in SLE patients who were positive for dsDNA autoantibodies. The IRF3 rs2304204 GG and AG genotypes conferred decreased risk for SLE. Our findings suggest that the predominant IRF3 expression on circulating pDC is a key element for the increased IFN-α activation based on the interplay between the rs2304206 gene variant and the presence of dsDNA autoantibodies in Mexican mestizo SLE patients.