Cline in genetic diversity of trehalase deficiency determinants in populations of Southern Siberia, Kazakhstan, Central Asia, and Mongolia

Abstract

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 (r_sp =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: r_sp =0.613 (p =0.007); with AA*TREH frequency r_sp =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

References

Kozlov A.I., Balanovsky O.P., Vershubskaya G.G., Gorin I.O., Balanovska E.V., Lavryashina M.B. Geneticheski determinirovannaya nedostatochnost' tregalazy v razlichnykh gruppakh naseleniya Rossii i sopredel'nykh stran [Genetically determined trehalase deficiency in various population groups of Russia and neighboring countries]. Voprosy pitaniia [Problems of Nutrition], 2021, 90 (5), pp. 96–103. (In Russ.). DOI: https: 10.33029/0042-8833-2021-90-5-96-103.

Kozlov A.I., Vershubskaya G.G., Gorin I.O., Pylev V.Yu., Balanovska E.V. Rasprostranennost' geneticheskikh determinant tregalaznoy enzimopatii v populyatsiyakh Sibiri i Dal'nego Vostoka Rossii [Prevalence of trehalase enzymopathy genetic determinants in Siberian and Russian Far East populations]. Voprosy pitaniia [Problems of Nutrition], 2023, 92 (2), pp. 53–59. (In Russ.). DOI: https:10.33029/0042-8833-2023-92-2-53-59.

Malyarchuk B.A., Derenko M.V. Polimorfizm gena tregalazy (TREH) u korennogo naseleniya Sibiri [Polymorphism of the trehalase gene (TREH) in the indigenous population of Siberia]. Vavilovskiy zhurnal genetiki i selektsii [Vavilov Journal of Genetics and Breeding], 2017, 21 (8), pp 964–968. (In Russ.). 

Ahmed A., Khan T.A., Ramdath D.D., Kendall C.W.C., Sievenpiper J.L. Rare sugars and their health effects in humans: a systematic review and narrative synthesis of the evidence from human trials. Nutrition Reviews, 2022, 80 (2), pp. 255–270. DOI: 10.1093/nutrit/nuab012.

Alexander D.H., Novembre J., Lange K. Fast model-based estimation of ancestry in unrelated individuals. Genome research, 2009, 19 (9), pp. 1655–1664.

Asp N.G., Berg N.O., Dahlquist A., Gudmand-Hoyer E., Jarnum S., McNair A. Intestinal disaccharidases in Greenland Eskimos. Scand. J. Gastroenterol., 1975, 10, pp. 513–519.

Cardwell G., Bornman J.F., James A.P., Black L.J. A review of mushrooms as a potential source of dietary vitamin D. Nutrients, 2018, 10 (10). Article ID pii: E1498. DOI: 10.3390/nu10101498.

Chang C.C., Chow C.C., Tellier L.C., Vattikuti S., Purcell S.M., et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience, 2015, 4, pp. 1–16.

Clemente F.J., Cardona A., Inchley C.E., Peter B.M., Jacobs G., et al. A selective sweep on a deleterious mutation in the CPT1A gene in Arctic populations. Am. J. Hum. Genet., 2014, 95, pp. 584–589.

Di Rienzi S.C., Britton R.A. Adaptation of the gut microbiota to modern dietary sugars and sweeteners. Adv. Nutrit., 2020, 11 (3), pp. 616–629.

Gudmand-Hoyer E., Fenger H.J., Skovbjerg H., Kern-Hansen P., Madsen P.R. Trehalase deficiency in Greenland. Scand. J. Gastroenterol., 1988, 23, pp. 775–778.

Higashiyama T., Richards A.B. Trehalose. In: Kay O’Donnell, Malcolm W. Kearsley (eds.). Sweeteners and Sugar Alternatives in Food Technology. 2nd ed., John Wiley & Sons Ltd., 2012, pp. 417–431.

Keegan R.-J.H., Lu Z., Bogusz J.M., Willians J.E., Holick M.F. Photobiology of vitamin D in mushrooms and its bioavailability in humans. Dermato-Endocrinol., 2013, 5 (1), pp. 165–176. DOI:10.4161/derm.23321.

Kozlov A., Vershubskaya G., Gorin I., Petrushenko V., Lavryashina M., Balanovska E. Prevalence of genetically determined trehalase deficiency in populations of Siberia and Russian Far East. Int. J. Circumpolar Health, 2023, 82 (1). 2183931. DOI: 10.1080/22423982.2023.2183931 DOI 10.1080/22423982.2023.2183931.

Manichaikul A., Mychaleckyj J.C., Rich S.S., Daly K., Sale M., Chen W.M. Robust relationship inference in genome-wide association studies. Bioinformatics, 2010, 26 (22), pp. 2867–2873.

Muller Y.L., Hanson R.L., Knowler W.C., Fleming J., Goswami J., et al. Identification of genetic variation that determines human trehalase activity and its association with type 2 diabetes. Hum. Genet., 2013, 132, pp. 697–707.

Murray I.A., Coupland K., Smith J.A., Ansell I.D., Long R.G. Intestinal trehalase activity in a UK population: establishing a normal range and the effect of disease. Brit. J. Nutr., 2000, 83, pp. 241–245.

Oku T., Nakamura S. Estimation of intestinal trehalase activity from a laxative threshold of trehalose and lactulose on healthy female subjects. Eur. J. Clin. Nutr., 2000, 54 (10), pp. 783–788. DOI: 10.1038/sj.ejcn.1601091.

Pagani L., Lawson D.J., Jagoda E., Mörseburg A., Eriksson A., et al. Genomic analyses inform on migration events during the peopling of Eurasia. Nature, 2016, 538, pp. 238–242.

Richards A.B., Krakowka S., Dexter L.B., Schmid H., Wolterbeek A.P., et al. Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies. Food Chem. Toxicol., 2002, 40 (7), pp. 871–898.

Sokolowska E., Sadowska A., Sawicka D., Kotulska-Bablinska I., Car H. A head-to-head comparison review of biological and toxicological studies of isomaltulose, d-tagatose, and trehalose on glycemic control. Crit. Rev. Food Sci. Nutr., 2021. DOI: 10.1080/10408398.2021.1895057.

Ushijima T., Fugisawa T., Kretchmer N. Evaluation of the ability of human small intestine to adsorb trehalose. Digest. Absorption., 1995, 18, pp. 56–57.

Van Laar A.D.E., Grootaert C., Van Camp J. Rare mono- and disaccharides as healthy alternative for traditional sugars and sweeteners? Crit. Rev. Food. Sci. Nutr., 2021, 61, pp. 713–741.

Welsh J.D., Poley J.R., Bhatia M., Stevenson D.E. Intestinal disaccharidase activities in relation to age, race, and mucosal damage. Gastroenterology, 1978, 75, pp. 847–855.