Common genetic variants in the glucocorticoid receptor and the 11β-Hydroxysteroid dehydrogenase type 1 genes influence long-term cognitive impairments in patients with Cushing's syndrome in remission.

• Context: Cognitive function is impaired in patients with Cushing's syndrome (CS) in remission. Objective: To study the effects of polymorphisms in genes associated with glucocorticoid (GC) sensitivity on cognitive function in patients with CS in long-term remission. Design: A cross-sectional, case-controlled, single center study. Patients: Fifty-three patients with Cushing's syndrome in remission and 53 controls matched for age, gender and educational level. Main Outcome Measures: Cognitive function, studied using standardized neuropsychological testing, and polymorphisms in the GC receptor (NR3C1; Bcl1 and A3669G), mineralocorticoid receptor (NR3C2; I180V), 11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1; rs11119328) and ATP binding cassette B1 (ABCB1; rs1045642) genes. The association between cognitive function and polymorphisms were analyzed using linear regression with adjustments for age and educational level. Results: The mean age in patients and controls was 53 ± 14 years. The median (interquartile range) duration of remission was 13 (5-18) years. In patients, SNP rs11119328 was associated with impairments in processing speed, auditory attention, auditory working memory and reading speed. This association was not seen in matched controls. The Bcl1 polymorphism was associated with fatigue and worse visual attention and working memory. The remaining SNPs were not associated with cognitive performance. Conclusion: In this study, polymorphisms in the 11βHSD1 and NR3C1 genes were associated with impaired cognitive function, indicating that GC sensitivity and pre-receptor regulation of GC action may play a role in the long-term consequences of CS. The study provides a novel insight into the etiology of cognitive dysfunction in patients with CS in remission.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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