High carrier frequency of a nonsense p.Trp230* variant in HSD3B2 gene in Ossetians

Front Endocrinol (Lausanne). 2023 May 16:14:1146768. doi: 10.3389/fendo.2023.1146768. eCollection 2023.

Abstract

Background: Congenital adrenal hyperplasia (CAH) caused by 3β-HSD deficiency is a rare form of congenital adrenal deficiency with an autosomal recessive type of inheritance. Previously we have demonstrated that a single nucleotide variant (SNV) p.Trp230* in the homozygous state is a frequent cause of CAH among the indigenous population of North Ossetia-Alania represented by Ossetians.

Methods: Genotyping of the NM_000198.3:c.690G>A p.Trp230* variant was performed by Real-time PCR. 339 healthy individuals of Ossetian origin were included in the study. Allele frequencies, Fisher's confidence intervals (CI) were calculated using the WinPepi v. 11.65 software. Comparison of allele frequencies was performed with the z-score test for two proportions.

Results: Eight heterozygous carriers of c.690G>A variant in HSD3B2 gene were detected in 339 samples investigated. The total allele frequency of p.Trp230* variant was 0.0118 (n=8/678, 95% CI=0.0051-0.0231). Accordingly, the heterozygous carrier rate was 0.0236 (n=8/339). The frequency of CAH caused by p.Trp230* variant in HSD3B2 in Ossetian population was 1:7183 or 13.9 per 100,000 (95% CI: 1:1874-1:38447 or 3-53 per 100,000).

Conclusion: The results demonstrate high frequency of p.Trp230* variant in Ossetians, which is most likely attributed to a founder effect.

Keywords: CAH; HSD3B2; Ossetians; deficiency of 3β-hydroxysteroid dehydrogenase; real-time PCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Hyperplasia, Congenital* / epidemiology
  • Adrenal Hyperplasia, Congenital* / genetics
  • Eastern European People
  • Homozygote
  • Humans
  • Progesterone Reductase* / genetics

Substances

  • 3 beta-hydroxysteroid dehydrogenase type II
  • Progesterone Reductase

Supplementary concepts

  • Ossetian people

Grants and funding

This work was supported grant from the President of the Russian Federation № МК-5272.2022.3. This study was also supported in part by the state assignment of the Ministry of Science and Higher Education of the Russian Federation.