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

To analyze whether telomere length, X-chromosome inactivation (XCI), and androgen receptor (AR) GAG polymorphism are related to idiopathic premature ovarian insufficiency (POI). Case–control study. University hospital. A total of 121 women, including 46 nonsyndromic POI and 75 controls. None. 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. 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. 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 Analizar si la longitud de los telómeros, la inactivación del cromosoma X (XCI) y el polimorfismo de los receptores de andrógenos (AR) GAG están relacionados con la insuficiencia ovárica prematura idiopática (PDI). Estudio de casos y controles. Hospital Universitario. Departamento de Ginecología y Obstetricia de la Facultad de Medicina de Ribeirao Preto, Universidad de Sao Paulo, Universidad de Campinas y Universidad Federal de Minas Gerais. Un total de 121 mujeres, incluyendo 46 POI no sindrómicas y 75 controles. Ninguna. Se evaluaron edad, peso, talla, índice de masa corporal (IMC), presión arterial sistólica y diastólica, E2, androstenediona, T, y la proteína C-reactiva. La longitud de los telómeros se estimó mediante la reacción en cadena de la polimerasa cuantitativa en tiempo real, y la XCI fue medida utilizando ensayos de metilación del Receptor de Andrógeno Humano