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

• Published in: PloS one 2017-11, Vol.12 (11), p.e0187365-e0187365
• Main Authors: Nedoszytko, Bogusław, Siemińska, Alicja, Strapagiel, Dominik, Dąbrowski, Sławomir, Słomka, Marcin, Sobalska-Kwapis, Marta, Marciniak, Błażej, Wierzba, Jolanta, Skokowski, Jarosław, Fijałkowski, Marcin, Nowicki, Roman, Kalinowski, Leszek
• Format: Article
• Language: English
• Subjects: 3-Hydroxyacyl-CoA dehydrogenase; Abetalipoproteinemia; Acyl-CoA Dehydrogenase, Long-Chain - chemistry; Acyl-CoA Dehydrogenase, Long-Chain - genetics; Adult; Adults; Amino Acid Substitution; Biology; Biology and Life Sciences; Biophysics; Carriers; Chains; Chi-square test; Chromosome 19; Chromosomes; Consortia; Dehydrogenase; Dehydrogenases; Dermatology; Engineering and Technology; Environmental protection; Enzymes; Ethnic Groups - genetics; Fatty acids; Founder effect; Gene polymorphism; Genetic diversity; Genetic variance; Genomes; Hereditary diseases; Heterozygote; High frequencies; Humans; Hypoglycemia; Metabolic disorders; Mitochondria; Mutation; Oligonucleotide Array Sequence Analysis; Oxidation; People and places; Peripheral neuropathy; Physical Sciences; Poland; Polymorphism; Polymorphism, Single Nucleotide; Population; Prevalence; Research and Analysis Methods
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0187365

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. 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. 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. 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.