Background: Polycystic ovarian syndrome (PCOS) and the non-classic form of congenital adrenal hyperplasia (NC-CAH) are hyperandrogenic conditions with overlapping clinical symptoms but different genetic backgrounds. The possible interrelationships between the two conditions remain unclear; thus, the present study aims to investigate the prevalence of CYP21A2 exon 7 genetic variants in patients with PCOS and to explore the possible associations of the polymorphisms with adrenocortical hormonal production. Methods: The CYP21A2 exon 7 region was genotyped in 80 unrelated female patients with PCOS and 12 women with NC-CAH. The associations between genetic variants, clinical characteristics, and adrenocortical hormones were investigated. Results: The pathogenic CYP21A2 NC-CAH variant c.844G>T; p.(Val282Leu) was found in 66.7% (8/12) of patients with NC-CAH but in none of the individuals with PCOS. The benign rs1554305325, rs6465, rs6472, and rs6477 genetic polymorphisms were not related to clinical hyperandrogenism. The rs6472 polymorphic alleles were associated with increased adrenocorticotropic hormone (ACTH) (5.5 vs. 3.4 pmol/L, p = 0.022) and cortisol (460.5 vs. 366.5 nmol/L, p = 0.016) levels. The rs6465 variant alleles were significantly associated with lower pregnenolone (1.43 vs. 3.1 ng/mL, p = 0.031) and ACTH (2.5 vs. 4.5 pmol/L, p = 0.030) levels in the unadjusted model but not after adjustment for potential confounders (p > 0.05). Conclusions: The p.(Val282Leu) variant is very common among Bulgarian patients with NC-CAH but it has not been found in our cohort of women with PCOS. The CYP21A2 exon 7 polymorphisms might be associated with cortisol levels in the patients with PCOS. Further larger studies are needed to confirm or reject the current findings in different ethnic groups.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial, highly prevalent liver disease in children. There is growing evidence that some genetic variants are associated with its development and rapid progression. The aim of this study was to assess the prevalence of specific single-nucleotide polymorphisms – PNPLA3 I148M, GCKR P446L, TM6SF2 E167K in Bulgarian children with NAFLD. We conducted a single-centre, prospective study of 32 children (22 patients with NAFLD and 10 healthy controls). Genetic testing and abdominal ultrasound were performed in all study participants. In the patients with NAFLD were additionally analyzed anthropometric parameters and standard biochemical tests, 10 of them underwent a liver biopsy for assessing disease activity and fibrosis. The most common polymorphism was GCKR P446L, detected in 75% of the studied population, followed by PNPLA3 I148M (50.0% of the studied population) and TM6SF2 E167K (9.4% of the studied population). The GCKRP446L gene variant was more common in patients with NAFLD than in healthy controls (86.4% vs. 50.0%, p = 0:03). Furthermore, significantly more patients with NAFLD were homozygous carriers of GCKR P446L compared to healthy controls (54.5% vs. 10.0%, p = 0:025). Both patients with histologically proven significant liver fibrosis were carriers of GCKR P446L. In the present study we found a high prevalence of GCKR P446L polymorphism among children with NAFLD, suggesting that this gene variant is associated with development of NAFLD in the Bulgarian pediatric population.