High prevalence of carriers of variant c.1528G>C of HADHA gene causing long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) in the population of adult Kashubians from North Poland

PLoS One. 2017 Nov 2;12(11):e0187365. doi: 10.1371/journal.pone.0187365. eCollection 2017.

Abstract

Background/objectives: The mitochondrial β-oxidation of fatty acids is a complex catabolic pathway. One of the enzymes of this pathway is the heterooctameric mitochondrial trifunctional protein (MTP), composed of four α- and β-subunits. Mutations in MTP genes (HADHA and HADHB), both located on chromosome 2p23, cause MTP deficiency, a rare autosomal recessive metabolic disorder characterized by decreased activity of MTP. The most common MTP mutation is long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency caused by the c.1528G>C (rs137852769, p.Glu510Gln) substitution in exon 15 of the HADHA gene.

Subjects/methods: We analyzed the frequency of genetic variants in the HADHA gene in the adults of Kashubian origin from North Poland and compared this data in other Polish provinces.

Results: We found a significantly higher frequency of HDHA c.1528G>C (rs137852769, p.Glu510Gln) carriers among Kashubians (1/57) compared to subjects from other regions of Poland (1/187). We found higher frequency of c.652G>C (rs71441018, pVal218Leu) polymorphism in the HADHA gene within population of Silesia, southern Poland (1/107) compared to other regions.

Conclusion: Our study indicate described high frequency of c.1528G>C variant of HADHA gene in Kashubian population, suggesting the founder effect. For the first time we have found high frequency of rs71441018 in the South Poland Silesian population.

MeSH terms

  • Acyl-CoA Dehydrogenase, Long-Chain / chemistry
  • Acyl-CoA Dehydrogenase, Long-Chain / genetics*
  • Adult
  • Amino Acid Substitution
  • Ethnicity / genetics*
  • Heterozygote*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Poland
  • Polymorphism, Single Nucleotide
  • Prevalence

Substances

  • Acyl-CoA Dehydrogenase, Long-Chain

Grants and funding

The study is financed by Polish Ministry of Science and Higher Education grant 02-0066/07/253 and DIR/WK/2017/01. POPULOUS collection was financed by the Polish POIG Grant 01.01.02-10-005/08 TESTOPLEK from the European Regional Development Fund. Sławomir Dąbrowski received salaries from A&A Biotechnology s.c. The funder provided support in the form of salaries for Sławomir Dąbrowski, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.