Abstract
Background/ObjectivesThe 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/MethodsWe 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.ResultsWe 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.ConclusionOur 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.
Highlights
The mitochondrial β-oxidation of fatty acids is a complex catabolic pathway in which at least 10 different enzymes are involved
mitochondrial trifunctional protein (MTP) has trifunctional enzymatic activity: it acts as long-chain enoyl-CoA hydratase (LCEH), long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and long-chain 3-ketothiolase (LKCT)
The LCHAD and LCEH activity is associated with its α-subunit (OMIM #600890), whereas LKCT activity is associated with the β-subunit (OMIM #143450) of MTP
Summary
The mitochondrial β-oxidation of fatty acids is a complex catabolic pathway in which at least 10 different enzymes are involved. One of the last enzyme of this pathway is the mitochondrial trifunctional protein (MTP), a heterooctameric protein composed of four α- and four β-subunits. MTP has trifunctional enzymatic activity: it acts as long-chain enoyl-CoA hydratase (LCEH), long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and long-chain 3-ketothiolase (LKCT). The α- and β-subunits of MTP are encoded by different genes (HADHA and HADHB), both located on chromosome 2p23 [1]. The most common MTP deficiency in Europe is the isolated long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency caused by c.1528G>C substitution on at least one allele of the HADHA gene [1,2,3,4,5,6,7,8,9,10,11,12]
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