RESUMO
Russell-Silver Syndrome (RSS) is a prenatal and postnatal growth retardation syndrome caused mainly by 11p15 ICR1 hypomethylation. Clinical presentation is heterogeneous in RSS patients with 11p15 ICR1 hypomethylation. We previously identified a subset of RSS patients with 11p15 ICR1 and multilocus hypomethylation. Here, we examine the relationships between IGF2 expression, 11p15 ICR1 methylation, and multilocus imprinting defects in various cell types from 39 RSS patients with 11p15 ICR1 hypomethylation in leukocyte DNA. 11p15 ICR1 hypomethylation was more pronounced in leukocytes than in buccal mucosa cells. Skin fibroblast IGF2 expression was correlated with the degree of ICR1 hypomethylation. Different tissue-specific multilocus methylation defects coexisted in 38% of cases, with some loci hypomethylated and others hypermethylated within the same cell type in some cases. Our new results suggest that tissue-specific epigenotypes may lead to clinical heterogeneity in RSS.
Assuntos
Cromossomos Humanos Par 11/genética , Metilação de DNA , Impressão Genômica , Fator de Crescimento Insulin-Like II/genética , Síndrome de Silver-Russell/genética , Adulto , Criança , Pré-Escolar , Epitélio/metabolismo , Fibroblastos/metabolismo , Expressão Gênica , Humanos , Recém-Nascido , Leucócitos/metabolismo , Mucosa Bucal/metabolismo , Especificidade de Órgãos , Pele/metabolismoRESUMO
BACKGROUND: Insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) are involved in oxidative stress and atherosclerosis; however, the relationship between the IGF-I system and atrial fibrillation (AF) is not known. The objective of this analysis was to assess, the relationship between IGF-I and IGFBP-3 serum levels and AF among elderly participants. METHODS: In this cross-sectional study, 719 participants (mean age [SD] years: 78.2 [6.8]; 31.8% men) were evaluated during an outpatient geriatric assessment. AF was determined by electrocardiogram or medical record. Participants were classified into two groups: Participants with AF (n = 91) or without AF (n = 628). IGF-I and IGFBP-3 serum levels were determined by enzyme linked immunosorbent assay. RESULTS: After adjusting for age and sex, the mean IGF-I and IGFBP-3 serum levels were significantly lower among AF participants than among non-AF participants (mean IGF-I ng/mL [SD] = 133.8 [66.6] vs 157.9 [80.0], p = .02; mean IGFBP-3 ng/mL [SD] = 3,653 [1,393] vs 4,151 [1,583], p = .03, respectively). After adjusting for confounding factors (age, gender, beta blocker medication, heart rate, hypertension, stroke, and chronic heart failure), low IGF-I serum level (OR [95% CI] = 0.66 [0.49-0.87]) and low IGFBP-3 serum level (0.71 [0.54-0.93]) remained independent determinants of AF. CONCLUSIONS: Low IGF-I and low IGFBP-3 serum levels were independently associated with AF in this elderly population. This result should be confirmed in a longitudinal study to evaluate whether IGF-I and/or IGFBP-3 serum levels are predictive of incident AF.