vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ21.51-ovavilov-3013Research ArticleГЕНЕТИКА ЧЕЛОВЕКАHUMAN GENETICSПолиморфизм генов, ассоциированных с инфекционными заболеваниями легких, в популяциях Северной Азии и среди пациентов с внебольничными пневмониямиPolymorphism of genes associated with infectious lung diseases in Northern Asian populations and in patients with community-acquired pneumoniahttps://orcid.org/0000-0002-0897-5473МихайловаС. В.MikhailovaS. V.

Новосибирск

mikhail@bionet.nsc.ruhttps://orcid.org/0000-0001-9270-9188ЩербаковаЛ. В.ShcherbakovaL. V.

Новосибирск

ЛогвиненкоН. И.LogvinenkoN. I.

Новосибирск

https://orcid.org/0000-0003-1348-0253ЛогвиненкоИ. И.LogvinenkoI. I.

Новосибирск

https://orcid.org/0000-0001-9425-413XВоеводаМ. И.VoevodaM. I.

Новосибирск

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияНаучно-исследовательский институт терапии и профилактической медицины – филиал Федерального исследовательского центра Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationНовосибирский государственный медицинский университет Министерства здравоохранения Российской ФедерацииРоссияNovosibirsk State Medical UniversityRussian FederationНаучно-исследовательский институт терапии и профилактической медицины – филиал Федерального исследовательского центра Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский государственный медицинский университет МинистерстваРоссияInstitute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State Medical UniversityRussian Federation202102062021253301309Copyright © Михайлова С.В., Щербакова Л.В., Логвиненко Н.И., Логвиненко И.И., Воевода М.И., 20212021Михайлова С.В., Щербакова Л.В., Логвиненко Н.И., Логвиненко И.И., Воевода М.И.Mikhailova S.V., Shcherbakova L.V., Logvinenko N.I., Logvinenko I.I., Voevoda M.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3013

Врожденный иммунитет первым отвечает на инфекцию. Он участвует в распознавании патогена, привлечении к месту заражения иммунных клеток, а также активирует адаптивный иммунитет и регулирует интенсивность воспалительного ответа. Для двух однонуклеотидных полиморфизмов (ОНП) генов врожденного иммунитета – rs5743708 (Arg753Gln) гена TLR2 и rs8177374 (Ser180Leu) гена TIRAP – была показана ассоциация одновременно с пневмонией и туберкулезом, однако полученные данные различаются для разных этнических групп. Для rs10902158, расположенного в генетическом локусе PKP3-SIGGIR-TMEM16J, ранее было показано, что он входит в гаплотип, расоспецифически ассоциированный с туберкулезом. При этом на тер ритории Азии наблюдается градиент его частоты. Целью нашей работы была оценка влияния отбора по генотипам названных ОНП на генофонды популяций, живущих в климатических условиях, неблагоприятных по инфекционным заболеваниям легких. Мы оценили распространение этих ОНП в выборках европеоидного и монголоидного (чукчи и якуты) населения Северной Азии и среди пациентов с внебольничной пневмонией. Носительство аллеля А rs5743708 гена TLR2 предрасполагало к развитию тяжелой внебольничной пневмонии (OR = 2.77, p = 0.021), а генотип GG/CT по rs5743708/rs8177374 оказался протективным против нее (OR = 0.478, p = 0.022) у европеоидов. Ассоциации rs10902158 с внебольничной пневмонией (как в целом, так и ее тяжелой формы) в европеоидной выборке обнаружено не было. Дифференцировка внебольничных пневмоний по их этиологии, возможно, позволит устранить наблюдаемые противоречия в данных разных исследователей об ассоциации исследованных ОНП с заболеванием. Не выявлено достоверных различий по частоте rs5743708 гена TLR2 и rs8177374 гена TIRAP между европеоидными выборками подростков и долгожителей. Вероятно, эти ОНП не влияют на предрасположенность к долгожительству в европеоидных популяциях, проживающих на Севере Евразии. Исследованные нами европеоидные и монголоидные популяционные выборки отличались по частотам вышеперечисленных вариантов от западноевропейских и восточноазиатских популяций. Частота варианта rs8177374 T (Ser180Leu) гена TIRAP в выборке чукчей была достоверно выше (p = 0, χ2 = 63.22), чем в популяциях Восточной Азии, что может служить подтверждением нашего предположения об отборе этого варианта в ходе миграции человека в районы с неблагоприятными климатическими условиями.

The innate Iнн\mmune system is the first to respond to invading pathogens. It is responsible for invader recognition, immune-cell recruitment, adaptive-immunity activation, and regulation of inflammation intensity. Previously, two single-nucleotide polymorphisms of innate-immunity genes – rs5743708 (Arg753Gln) of the TLR2 gene and rs8177374 (Ser180Leu) of the TIRAP gene – have been shown to be associated with both pneumonia and tuberculosis in humans, but the data are contradictory among different ethnic groups. It has also been reported that rs10902158 at the PKP3-SIGGIR-TMEM16J genetic locus belongs to a haplotype race-specifically associated with tuberculosis. Meanwhile, a gradient of its frequency is observed in Asia. The aim of this work was to assess the effect of selection for the genotypes of the above-mentioned SNPs on the gene pools of populations living in harsh climatic conditions that contribute to the development of infectious lung diseases. We estimated the prevalence of these variants in white and Asian (Chukchis and Yakuts) population samples from Northern Asia and among patients with community-acquired pneumonia (CAP). Carriage of the rs5743708 A allele was found to predispose to severe CAP (odds ratio 2.77, p = 0.021), whereas the GG/CT genotype of rs5743708/rs8177374 proved to be protective against it (odds ratio 0.478, p = 0.022) in white patients. No association of rs10902158 with CAP (total or severe) was found among whites. Stratification of CAP by causative pathogen may help eliminate the current discrepancies between different studies. No significant difference in rs5743708 or rs8177374 was found between adolescent and long-lived white samples. Carriage of the alleles studied is probably not associated with predisposition to longevity among whites in Siberia. Both white and Asian populations studied were different from Western European and East Asian populations in the variants’ prevalence. The frequency of the rs8177374 T (Ser180Leu) variant was significantly higher in the Chukchi sample (p = 0, χ2 = 63.22) relative to the East Asian populations. This result may confirm the hypothesis about the selection of this allele in the course of human migration into areas with unfavorable climatic conditions.

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The authors declare that there are no conflicts of interest present.