A pilot study of inherited carnitine palmitoyltransferase deficiency as an ethnogenetic risk factor of infant mortality in indigenous populations of the Far North

A common variant of inherited deficiency of type 1A carnitine palmitoyltransferase (CPT1A) first detected in Canadian Inuits has also been detected in the indigenous populations of various regions of Alaska, northern Canada, and Greenland. However, the prevalence of the P479L genotype in neonates has not been evaluated to date. The frequency of the P479L allele in two populations of Taymyr Peninsula (Dolgan-Nganasan and Nenets) has been assessed in the study. Dried blood spots from newborns born in 2010–2013 were collected in two populations: 108 samples were collected from Dolgan-Nganasans (the settlements Syndasko, Kataryk, and Levinskie Peski) and 105 samples were collected from Nganasans (the Nosok settlement). Allelic variants c.1436C/T (rs 80356779) of the carnitine palmitoyltransferase (CPT1A) gene were investigated in these samples. Genotyping for the P479L mutation was based on analysis of restriction fragment length polymorphism. DNA extracted from the dried blood spots was initially amplified using polymerase chain reaction with the following primers: 5’-CTGGCCAGGTTTGGATTTT-3’ and 5’-TCCAGGATGAAGCAGAGAGG-3’. Restriction endonuclease BstMC (SibEnzim, Novosibirsk, Russia) was used for restriction of the amplicons obtained: a 252-bp fragment was obtained after restriction if the subject carried the T-allele, and an 83-bp fragment was obtained if the subject carried the C-allele. There was a distinct difference in the frequency of the P479L genotype between the two populations, with seven heterozygotes identified in the Dolgan-Nganasan population (7/108; 0.07; 95% confidence interval, 0.03–0.13) and no carriers of the mutant gene identified in the Nenets population (0/105), p = 0.006. The frequency of the rare T-allele in the Dolgan-Nganasan population was 0.03. The results of the study support the hypothesis of the influence of the traditional diet and “evolutionary advantage” for carriers of the P479L mutation residing in certain Arctic regions. We assume that a certain increase in the prevalence of the genetic variant P479L in the Dolgan population may be due to proximity of the area of residence to the coast and adherence to a high-fat diet. Furthermore, we believe that our data and the results of similar studies addressing the frequency of the P479L mutation can be successfully used for the analysis of the origin and migration of certain indigenous peoples of the Far North.