Gene polymorphism of mannose-binding lectin-associated serine protease (MASP2) in indigenous populations of the Russian Arctic Territories

Mannose-binding lectin-associated serine proteases (MASP) are among of the key components in the lectin pathway (LP) of the complement activation. MASP-2 is the most studied agent among specific enzymes activating both mannose-binding lectin (MBL) and ficolins, pattern-recognition proteins involved in the elimination of pathogenic microorganisms through LP complement activation. There are some mutations in MASP2, with the most significant identified as rs72550870 (p.D120G). The homozygous GG rs72550870 is associated with congenital MASP-2 deficiency and characterized by a total lack of serum protease activity, which leads to impaired binding to lectins. This, in turn, results in severe course of infectious diseases with a high risk of adverse outcome. There seem to be some marked populational differences in the genotype and haplotype prevalence in MASP2 gene polymorphisms. To date, no data are available on the genotype distribution for the MASP2 gene in the indigenous populations of the Russian Arctic regions. The aim of the work was to study the prevalence and ethnic specificity in the distribution of allelic variants of MASP2 rs72550870 in the populations of the Taymyr Dolgan-Nenets District of the Krasnoyarsk Territory (Nenets, Dolgans, Nganasans) as well as the city of Krasnoyarsk (Russians). MASP2 genotyping was performed by using real-time PCR. The frequencies of the AG genotype associated with low MASP-2 level was 6.6% for ethnic Russian newborns in the Eastern Siberia. The prevalence of the AG genotype was significantly lower in newborns of the Arctic populations than in the Russians, being 0.3% and 0.9% for the Nenets and the Dolgan-Nganasans, respectively, which is close to the prevalence values identified for Asian and African populations (0%). No homozygous GG rs72550870 associated with congenital MASP-2 deficiency in newborns of the indigenous populations of the Taymyr Dolgan-Nenets region of Krasnoyarsk Territory (Nenets and Dolgan-Nganasans) and ethnic Caucasian subjects of the Krasnoyarsk city was detected. The frequency of the rare allelic variant G rs72550870 in ethnic Russian subjects was 3.3%, being close to the frequencies in the European populations of the world (4.0%), whereas it was 0.5% in the indigenous inhabitants of the Arctic Region. We have suggested that isolated Arctic populations encounter some intracellular infections historically later and, as contrasted with Caucasoid populations, retained a high activity in the lectin pathway of the complement activation established at the early stage of human evolution.