Cline in genetic diversity of trehalase deficiency determinants in populations of Southern Siberia, Kazakhstan, Central Asia, and Mongolia
Authors:   Lomonosov Moscow State University, Anuchin Research Institute and Museum of Anthropology, Mokhovaya st., 11, Moscow, 125009, Russia, Kozlov Andrew I. ,   Research Centre of Medical Genetics, Moskvorechye st., 1, Moscow, 115522, Russia,   National Research University – Higher School of Economics, Myasnitskaya st., 11, Moscow, 101000, Russia, Pylev Vladimir Yu. ,   Research Centre of Medical Genetics, Moskvorechye st., 1, Moscow, 115522, Russia,   Biobank of North Eurasia, Kotlyakovskaya st., 3-12, Moscow, 115201, Russia, Vershubskaya Galina G. ,   Lomonosov Moscow State University, Anuchin Research Institute and Museum of Anthropology, Mokhovaya st., 11, Moscow, 125009, Russia, Balanovska Elena V. ,   Research Centre of Medical Genetics, Moskvorechye st., 1, Moscow, 115522, Russia
Published: October 2023

Introduction. Trehalose or mushroom sugar has been increasingly used in the food industry in the past decades. To be absorbed in the human intestine, trehalose needs to be broken down by an enzyme known as trehalase. Today, it is known that the G→A substitution in the rs2276064 locus of the TREH gene results in the reduced activity of this enzyme. The aim of this study was to analyze the frequency of TREH (rs2276064) alleles and genotypes in the populations of South Siberia, Kazakhstan, Central Asia and Mongolia that differ in the contribution of the ancestral East Eurasian (Mongoloid) component to their gene pools. Methods. We genotyped 987 DNA samples collected from the representatives of 17 indigenous populations from Siberia, Kazakhstan and Mongolia. The samples of 311 ethnic Russians comprised a reference dataset. In addition to estimating the frequencies of TREH alleles and genotypes, we analyzed the contribution of the ancestral East Eurasian (Mongoloid) and West Eurasian (European) ADMIXTURE components for the studied populations using an Illumina 750k microarray of SNP markers. Results. The frequency of the A*TREH allele associated with trehalase deficiency increases from west to east (rsp =0.500, p <0.05). TREH is correlated more strongly with the contribution of the ancestral East Eurasian (Mongolian) component than with the geography of the studied populations: rsp =0.613 (p =0.007); with AA*TREH frequency rsp =0.688 (p =0.002). Conclusions. The rs2276064-А TREH allele is more frequent than previously estimated from clinical data. The more substantial is the contribution of the ancestral East Eurasian (Mongoloid) component, the higher is the frequency of the risk A*TREH allele, which rises dramatically to 29-30% in the Kyrgyz, Khakass, Tuvinian and 39% in Khalkha Mongol populations. Together, carriers of the AG and AA*TREH genotypes make up 35% to 65% of the populations of Oriental origin. We hypothesize that the high frequency of genetic trehalase deficiency determinants in the populations of Siberia, Kazakhstan, Central Asia, and Mongolia is associated with their anthropological characteristics and is not purely dependent on geographic factors. @ 2023. This work is licensed under a CC BY 4.0 license