Skewed X-chromosome inactivation and shorter telomeres associate with idiopathic premature ovarian insufficiency

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Artigo de periódico

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Objective To analyze whether telomere length, X-chromosome inactivation (XCI), and androgen receptor (AR) GAG polymorphism are related to idiopathic premature ovarian insufficiency (POI). Design Case–control study. Setting University hospital. Patient(s) A total of 121 women, including 46 nonsyndromic POI and 75 controls. Intervention(s) None. Main Outcome Measure(s) Age, weight, height, body mass index (BMI), systolic and diastolic arterial pressure, E2, androstenedione, T, and C-reactive protein were assessed. Telomere length was estimated by quantitative real-time polymerase chain reaction, XCI was measured using the Human Androgen Receptor and X-linked retinitis pigmentosa 2 (RP2) methylation assays. AR and FMR1 polymorphism was assessed by quantitative fluorescent polymerase chain reaction and sequencing. Result(s) Premature ovarian insufficiency women had a higher mean age, weighed less, and exhibited lower C-reactive protein, E2, and androstenedione levels. The AR polymorphism did not differ between the groups. Four patients had premutation (55–200 CGG repeats), and none displayed a full mutation in the FMR1 gene. However, patients with POI showed shorter telomere length and higher frequency of skewed XCI. Extreme skewing (≥90%) was observed in 15% of women with POI, and shorter telomeres correlated with XCI skewing in both groups. Conclusion(s) Skewed XCI and shortened telomere length were associated with idiopathic POI, despite no alterations in the AR and FMR1 genes. Additionally, there is a tendency for women with short telomeres to exhibit skewed XCI. La inactivación sesgada del cromosoma X y los telómeros más cortos se asocian con insuficiencia ovárica prematura idiopática

Abstract

Assunto

Medicina, Genomas

Palavras-chave

Anovulation, Epigenetic mechanisms, DNA methylation, Trinucleotide repeats, Genomic instability

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https://www.sciencedirect.com/science/article/pii/S001502821830342X?via%3Dihub

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