Adolescent polycystic ovary syndrome without obesity: HOTAIR rs1443512 genotype relates to fat mass and to the redistribution of fat mass on low-dose pioglitazone

• Published in: Journal of endocrinological investigation 2024-04, Vol.47 (4), p.1037-1043
• Main Authors: de Zegher, F., Díaz, M., Ibáñez, L.
• Format: Article
• Language: English
• Subjects: Absorptiometry; Adipogenesis; Adolescent; Alleles; Amenorrhea; Antisense RNA; Body composition; Body fat; Dual energy X-ray absorptiometry; Endocrinology; Female; Genotype; Genotype & phenotype; Genotypes; Girls; Humans; Internal Medicine; ISRCTN; ISRCTN11062950; ISRCTN29234515; ISRCTN45546616; Lipogenesis; Magnetic resonance imaging; Medicine; Medicine & Public Health; Metabolic Diseases; Metformin; Metformin - therapeutic use; Obesity; Obesity - drug therapy; Ovaries; Pioglitazone; Pioglitazone - therapeutic use; Polycystic ovary syndrome; Polycystic Ovary Syndrome - drug therapy; Rapid Communication
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-023-02206-0

Introduction Adolescent polycystic ovary syndrome (PCOS) is characterized by androgen excess and oligo-amenorrhea, and often results from ectopic lipid storage due to a mismatch between early adipogenesis and later lipogenesis. Endogenous HOX transcript antisense RNA (HOTAIR) and exogenous pioglitazone are enhancers of subcutaneous adipogenesis, particularly in the gluteofemoral region. The A allele of HOTAIR rs1443512 is an equivalent of a natural knock-down and is, thus, a candidate to influence the distribution of fat mass, and also the redistribution of fat mass by pioglitazone in adolescent PCOS-without-obesity. Subjects and methods We performed two post hoc analyses by HOTAIR rs1443512 genotype. In the first, we analyzed the pooled pre-treatment data (auxology; endocrinology; body composition by dual X-ray absorptiometry; abdominal fat distribution by magnetic resonance imaging) of 65 adolescent girls with PCOS-without-obesity in three reported studies (ISRCTN45546616; ISRCTN29234515; ISRCTN11062950). In the second, we analyzed the results of 24 adolescent girls with PCOS-without-obesity, who received pioglitazone (7.5 mg/d for 1 year) as part of a randomized combination treatment (with spironolactone and metformin) in two reported studies (ISRCTN29234515; ISRCTN11062950). All data had been obtained in a blinded-to-genotype way. Results The pre-treatment data disclosed that the girls-with-A-allele of HOTAIR rs1443512 had developed PCOS with a lower BMI (22.3 ± 2.3 kg/m 2 ; N  = 17) than the other girls (24.1 ± 2.7 kg/m 2 ; N  = 48), this difference being essentially attributable to a lower fat mass (mean difference 4.6 kg; P