Lipoprotein particle alterations due to androgen therapy in individuals with dyskeratosis congenita

• Published in: EBioMedicine Vol. 75; p. 103760
• Main Authors: Thompson, Mone't B., Muldoon, Daniel, de Andrade, Kelvin C., Giri, Neelam, Alter, Blanche P., Savage, Sharon A., Shamburek, Robert D., Khincha, Payal P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2022; Elsevier
• Subjects: Androgen; Androgens - adverse effects; Apolipoproteins B; Bone marrow failure; Cholesterol; Dyskeratosis congenita; Dyskeratosis Congenita - drug therapy; Dyskeratosis Congenita - genetics; Dyskeratosis Congenita - metabolism; HDL; Humans; LDL; Lipid; Lipoprotein; Lipoprotein particle; Lipoproteins; NMR; Telomere; Telomere - metabolism; HDL; NMR; Bone marrow failure; Androgen; LDL; Dyskeratosis congenita; Lipoprotein particle; Lipoprotein; Telomere; Lipid; Cholesterol
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2021.103760

Dyskeratosis congenita (DC) is a telomere biology disorder associated with high rates of bone marrow failure (BMF) and other medical complications. Oral androgens are successfully used to treat BMF in DC but often have significant side effects, including elevation of serum lipids. This study sought to determine the extent to which oral androgen therapy altered lipid and lipoprotein levels. Nuclear magnetic resonance (NMR) was used to evaluate serum lipid profiles, and lipoprotein particle number and size in nine androgen-treated individuals with DC, 45 untreated individuals with DC, 72 unaffected relatives of DC patients, and 19 untreated individuals with a different inherited BMF syndrome, Fanconi anaemia (FA). Androgen-treated individuals with DC had significantly decreased serum HDL cholesterol, HDL particle number and HDL particle size (p < 0·001, p < 0·001 and p < 0·001, respectively); significantly increased serum LDL cholesterol and LDL particle number (p < 0·001, p < 0·001, respectively), decreased apoA-I and increased apoB (p < 0⋅001, p < 0⋅05 respectively) when compared with untreated individuals with DC. There were no significant lipid profile differences between untreated DC and untreated FA participants; or between untreated DC participants and their unaffected relatives. Branched chain amino acids and lipoprotein insulin resistance were not significantly different with androgen treatment. GlycA, an inflammatory acute phase reactant, was significantly increased with androgen treatment (p < 0⋅001). Androgen treatment in DC creates an atherogenic lipoprotein profile, raising concern for the potential of elevated cardiovascular disease risk. Clinical guidelines for individuals on androgens for DC-related BMF should include cardiovascular disease monitoring. These findings could be relevant in individuals treated with androgen for other indications. Intramural research programs of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute and National Heart, Lung, and Blood Institute.