The prevalence of the variants of the L-ficolin gene (FCN2) in the arctic populations of East Siberia

2022

Vestn. VOGiS

Lectins, being the main proteins of the lectin pathway activating the complement system, are encoded by polymorphic genes, wherein point mutations cause the protein conformation and expression to change, which turns out to have an effect on the functionality and ability to respond to the pathogen. In the current study, largescale data on the population genotype distribution of the genes for H-ficolin FCN3 rs28357092 and mannose-binding lectin-associated serine protease MASP2 rs72550870 among the indigenous peoples of the Russian Arctic regions (Nenets, Dolgans and Nganasans, a mixed population and Russians: a total sample was about 1000 newborns) have been obtained for the first time. Genotyping was carried out using RT-PCR. The frequency of the homozygous variant del/del FCN3 rs28357092 associated with the total absence of the most powerful activator of the lectin complement pathway, N-ficolin, was revealed; 0 % in the Nenets, 0.8 % in the Dolgans and Nganasans, and 3.5 % among the Russians ( p < 0.01). Analysis of the prevalence of the MASP2 genotypes has shown the predominance of the homozygous variant AA in all studied populations, which agrees with the available world data. The heterozygous genotype AG rs72550870 associated with a reduced level of protease was found to occur rarely in the Nenets, Dolgans and Nganasans compared to newborns of Caucasoid origin from Krasnoyarsk: 0.5 % versus 3.3 %, respectively. Moreover, among 323 examined Nenets, one AG carrier was identified, whereas in Russians, 16 out of 242 examined newborns were found to be AG carriers ( p < 0.001). A homozygous variant (GG) in total absence of protease with impaired binding of both MBL and ficolins was not detected in any of the 980 examined newborns. An additional analysis of infectious morbidity in Arctic populations allows one to find phenotypic characteristics related to a high functional activity of the lectin pathway of complement activation as an most important factor for the first-line of anti-infectious defense, including such new viral diseases as COVID-19.

Section: Resultsmentioning

confidence: 98%

mentioning

confidence: 88%

Prevalence of the polymorphic H-ficolin (FCN3) genes and mannosebinding lectin-associated serine protease-2 (MASP2) in indigenous populations from the Russian Arctic regions

2022

Vestn. VOGiS

“…В настоящем исследовании нами впервые получены данные о частотах генотипов и гаплотипов гена MBL2 среди коренных народностей, проживающих на территориях Арктической зоны Российской Федерации. Ранее нами была показана большая частота распространенно сти генотипов, ассоциированных с высокой активностью Lфиколина, в арктических популяциях ненцев и долган нганасан, в сравнении с европеоидами Восточной Сибири (Smolnikova et al, 2017). Таким образом, популяции коренных народов Арктики генетически характеризуются большей активностью как минимум двух различающихся компонентов лектинового пути активации комплемента -MBL и Lфиколина.…”

Section: результаты и обсуждениеunclassified

“…Таким образом, по результатам настоящего исследования нами показана большая частота встречаемости MBLвы сокопродуцирующих генетических вариаций в популяциях коренных арктических народностей, проживающих в Таймырском ДолганоНенецком районе Красноярского края. Рассматривая представленные данные в совокупности с ранее опубликованными результатами полиморфизма гена Lфиколина в тех же популяциях (Smolnikova et al, 2017), можно говорить не только о накоплении отдельных генотипов MBL2 и FCN2 в арктических популяциях, но и о большем тонусе лектинового пути активации комплемента в целом. Указанные факты позволяют нам осторожно высказаться о гипотезе селективного популяционного давления в отношении лектинового пути активации комплемента как общего патофизиологического механизма, опосредованного генами MBL2 и FCN2, и, вероятно, ассоциированного с предрасположенностью к некоторым инфекциям.…”

Section: заключениеunclassified

Polymorphism of the mannose-binding lectin gene in the Arctic indigenous populations of the Russian Federation

2020

Vestn. VOGiS

Mannose-binding lectin (MBL) is a pattern recognizing acute-phase protein of the innate immunity system actively involved in the elimination of a wide range of pathogenic microorganisms by activating the lectin pathway of the complement system. A significant part of the human population has a congenitally low production level and/or low MBL activity due to the carriage of various MBL2 variants, which can modify the course of a wide range of infectious diseases. The genotype and haplotype frequencies of the MBL2 polymorphisms have significant population differences. So far, data on the prevalence of the MBL2 genotypes in indigenous populations of the Russian Arctic regions have not been available. The aim of the study was to analyze the frequency and ethnic specificity of the distribution of allelic variants of the MBL2 polymorphisms rs11003125, rs7096206, rs7095891, rs5030737, rs1800450 and rs1800451 and their haplotypes in the populations of the Taimyr Dolgans-Nenets region of the Krasnoyarsk territory (Nenets, Dolgans-Nganasans, Russians). Data on the genotype and haplotype frequencies of the MBL2 gene among indigenous peoples of the Russian Arctic territories was first obtained in the study. The HYPA haplotype prevalence associated with a high concentration of MBL amounted to 35.4 % for Russian newborns in Eastern Siberia, corresponding to the one for European populations (27–33 %). In newborns of the Arctic populations, the prevalence of HYPA haplotype was significantly higher than in Russians and amounted to 64 % for Nenets and 56 % for the DolgansNganasans, which is close to the one detected for the Eskimos and North American Indians (64–81 %). Populations of Nenets and Dolgans-Nganasans demonstrated a significantly lower prevalence of MBL-deficient haplotypes compared with Caucasians of Eastern Siberia (3.9, 6.4 and 21.3 % respectively). Isolated Arctic populations were suggested to experience some intracellular infections (tuberculosis, leprosy) historically later and, unlike Caucasoid populations, to retain the high activity of the lectin complement activation pathway formed in the early stages of human evolution.

“…Показано, что в легких в наибольшей степени продуцируется H-фиколин, а его комплементсвязывающая способность превышает таковую MBL [10]. Показаны значительные популяционные различия в распределении генотипов гена FCN2, предположительно ассоциированные с его концентрацией и функциональной активностью [37].…”

Section: роль врожденного дефицита/дисфункции коллектинов в предраспоunclassified

Congenitally impaired pattern-recognition receptors in pathogenesis of pediatric invasive and recurrent pneumococcal infection

Russian Journal of Infection and Immunity

2019

Here we review currently available data showing that innate immune signs predisposing to recurrent and invasive pneumococcal infections were identified in children. Streptococcus pneumoniae (pneumococcus) belongs to Grampositive bacteria being the major cause of morbidity and mortality in infants, especially in developing countries and in communities with low socioeconomic status. Due to the lack of anti-pneumococcal vaccination, the significant proportion of pneumococcus carriers develop non-invasive (pneumonia, otitis media, sinusitis) and severe invasive (bacteremia/septicemia, meningitis) pneumococcal infection. A great deal of diverse factors related to pneumococcus biological features (virulence factors) as well individualized host-specific immunity are implicated in efficient bacterial penetration across the mucous membranes. The TLR signaling system plays a crucial role in the human nonspecific defense upon the first encounter with the pathogen. Various TLRs comprise the first pattern recognition receptor fami ly ever described which sense ligands derived from the outer bacterial wall. The complement system is the ancient innate immunity component mainly involved in intravascular elimination of bacterial agents. In addition, the complement proteins serve as a bridge between innate and adaptive immunity, ensuring optimal conditions for B- and T-cell maturation and differentiation. Because pneumococcus secretes the IgA protease, a local protective effects related to IgA antibodies might not be so prominent. Therefore, B-cell immunodeficiency and impaired complement system hold a lead place among congenital causes resulting in severe and recurrent pneumococcal infections in children. Thus, based on available data, we concluded that impaired B-cell function, the complement components deficiency as well as receptor-recognition receptors (TLR-2, -9, -4, MYD88 adapter protein, TLR cascade enzymes: IRAK4, NEMO, NOD-like receptors: NOD2, NLRP3; C-type lectins: MBL, Dextin-2, and, possibly, ficoline) play the most important role among congenital immunodeficiencies predisposing to invasive and recurrent pneumococcal infections play the most important role among congenital immunodeficiencies predisposing to invasive and recurrent pneumococcal infections, and should be used as a rationale for immunological surveillance and organizing immunogenetics screening in these patients.