Genetic and clinical markers of lactase deficiency in adolescents in the central and southern regions of Eastern Siberia
Authors:   Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences”, Research Institute of Medical Problems of the North: Krasnoyarsk, RU, Tereshchenko S.Yu. , Shubina M.V. ,   Research Institute of Medical Problems of the North: Krasnoyarsk, RU, Gorbacheva N.N. ,   Scientific Research Institute of medical problems of the North: Krasnoyarsk, Krasnoyarsk krai, RU
Published: December 2024

Research objective: to establish the genotype frequency of single nucleotide polymorphisms rs4988235 and rs182549 of the MCM6 gene depending on the ethnicity of adolescents in Eastern Siberia (Russians, Khakasses, Tuvans) and to identify the relationship between lactase deficiency (LD) and the clinical characteristics of recurrent abdominal pain (RAP).
Materials and Methods: 449 adolescents aged 11-18 years old were examined at schools in three cities of Siberia (Krasnoyarsk, Abakan, Kyzyl) and in-patient hospital in Krasnoyarsk. Lactase deficiency (LD) was diagnosed by the hydrogen breath test (HBT) after oral lactose load using the Gastrolyzer apparatus (Bedfont, UK). In schoolchildren, genomic DNA was isolated from saliva samples by the sorption method using the DIAtom DNA Prep kits (IsoGen, Russia). In inpatient children, DNA was isolated from whole blood by the sorption method from 0.1 ml of a suspension of leukocytes using the DNA-Sorb-B kit (103-20, AmpliPrime, Russia). Genotyping for the carriage of allelic variants rs4988235 and rs182549 of the MCM6 gene was performed on the basis of TaqMan allelic discrimination technology using real-time polymerase chain reaction (RT-PCR) on a detecting thermal cycler «Rotor-Gene 6000» (Corbett Life Science, Australia).
Results: The CC genotype of the rs4988235 polymorphism of the MCM6 gene occurs almost 5 times more often (93%) with a positive HBT than with a negative HBT (22%), p<0.001. Moreover, carriage of the rs4988235*CC genotype has a high sensitivity for LD diagnostics, i.e. 93 (81-99) %, with a relatively low specificity of 77 (69-85) %, which is likely to be due to the presence of secondary LD. A significantly higher prevalence of CC genotypes of both polymorphisms associated with LD has been observed in Mongoloid adolescents (Khakas - 82% and Tuvans - 91%), compared with Russian adolescents - 49%, p<0.001. There was no relationship between genetic markers of LD and RAP, verified according to the J. Apley and N. Naish criteria.
Conclusion: A high diagnostic significance of the rs4988235*CC genotype for LD diagnostics in Siberian adolescents was established. The СС genotype prevalence of both polymorphisms, associated with LD, in Russian adolescents (49%) does not differ from European data, whereas these genotypes were found in the great majority of Mongoloids examined (82-91%), which can be considered to be "paradoxical", given that the southern regions of Central Siberia are characterized by a historically high level of dairy farming development.
Keywords: lactase deficiency, adolescents, hydrogen breath test (HBT), genetic polymorphisms, recurrent abdominal pain.