vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ17.246vavilov-956Research ArticleГенетика человекаHuman geneticsПолиморфизм гена холодового рецептора TRPM8 у коренного населения Сибири: возможное адаптивное значение полиморфизма rs11563208 на северо-востоке АзииPolymorphism of the cold receptor gene TRPM8 in native populations of Siberia: putative selective role of rs11563208 polymorphism in Northeast AsiaМалярчукБ. А.MalyarchukB. A.

Магадан

Magadan

malyarchuk@ibpn.ruДеренкоМ. В.DerenkoM. V.

Магадан

Magadan

Федеральное государственное бюджетное учреждение науки Институт биологических проблем Севера Дальневосточного отделения Российской академии наукРоссияInstitute of Biological Problems of the North FEB RASRussian Federation201723052017213290295Copyright © Малярчук Б.А., Деренко М.В., 20172017Малярчук Б.А., Деренко М.В.Malyarchuk B.A., Derenko M.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/956

Ген TRPM8 кодирует холодовой рецептор TRPM8, имеющий большое значение в процессах адаптации к холоду, а также в процессах метаболизма и иммунного ответа. Ранее было обнаружено, что варианты полиморфизма гена TRPM8, распространенные в популяциях человека, ассоциируются с различной чувствительностью к холоду. В настоящей работе исследована изменчивость всех экзонов и прилегающих интронных последовательностей этого гена в выборках коренного населения Сибири, представляющего региональные группы Северо-Восточной, Центральной, Южной и Западной Сибири. Из 21 вариабельного локуса в девяти случаях частота производных аллелей составила более 10 % (локусы rs28901637, rs11562975, rs10929319, rs28901644, rs7593557, rs12185590, rs10171428, rs11563208, rs11563071). Различные варианты этих наиболее частых у коренного населения Сибири полиморфных локусов формируют 26 гаплотипов. Помимо общих для всех региональных выборок гаплотипов (7 гаплотипов, распространенных с частотой 2–28 %), в каждой из проанализированных выборок выявлены уникальные гаплотипы. Из них большой интерес представляет гаплотип, характеризующийся производным аллелем T в локусе rs11563208 и распространенный с частотой 14 % на северо-востоке Азии (у коряков и чукчей). Синонимичная замена в локусе rs11563208 может иметь функциональное значение, поскольку соответствующая этому локусу аминокислота (изолейцин в позиции 1016 белка TRPM8) расположена в функционально важном TRP-домене и, следовательно, может повлиять на процессы терморецепции. Предполагается также, что появление гаплотипа, несущего аллель rs11563208-T, обусловлено необходимостью противодействовать ингибированию рецепторов TRPM8 со стороны полиненасыщенных жирных кислот, которыми обогащена традиционная диета коренного населения северо-востока Азии (эскимосов, чукчей и коряков).

The TRPM8 gene encodes the cold-activated receptor TRPM8, which has an important role in cold adaptation as well as in metabolic and immune responses. Previously, it has been found that polymorphic variants of the TRPM8 gene, which are present in human populations, are associated with different cold sensitivity. In the present study we have investigated variability of all exons and adjacent intronic sequences of this gene in samples of native populations of Siberia, including regional groups from Northeastern, Central, Southern and Western parts of Siberia. In 9 out of 21 variable loci revealed, the frequency of the derived alleles accounts for more than 10 % (loci rs28901637, rs11562975, rs10929319, rs28901644, rs7593557, rs12185590, rs10171428, rs11563208, and rs11563071). Different variants of these polymorphic loci, which are most frequent in native Siberians, generate 26 haplotypes. In addition to 7 haplotypes shared by all regional groups and present there at frequencies of 2–28 %, unique haplotypes were found in all regional samples. One of them characterized by derived allele T at rs11563208 locus is very interesting because it is spread at the frequency of 14 % only in Northeast Asia (in Koryaks and Chukchi). A synonymous substitution at rs11563208 locus may have a functional role because the amino acid residue (isoleucine at position 1016 of TRPM8 protein) corresponding to this locus is located in functionally important TRP-domain and, hence, it can influence thermoreception processes. It is assumed that the appearance of the haplotype carrying the rs11563208-T allele may be due to the necessity to counteract the inhibition of TRPM8 receptors by polyunsaturated fatty acids, which are typical of the traditional diet of native people of Northeast Asia (Siberian Eskimo, Chukchi and Koryaks).

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