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

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.