Background. The aim of the study is to investigate the association of expression of galectin-9 (Gal-9) mRNA and lactose malabsorption in obese children with polymorphism (SNP) of the lactase gene (LCT) and to study the efficacy of lactase deficiency therapy using exogenous lactase preparations. Materials and methods. Seventy obese children (BMI > 95th percentile) and 16 children without obesity aged 6–18 years were examined. There was studied SNP LCT (material for investigation venous blood) by real-time PCR, expression of Gal-9 mRNA (study material buccal epithelium) by real-time PCR with reverse transcription, malabsorption of lactose by hydrogen breath test (HBT). Among obese children, 38 children with genotype C/C 13910 presented the first observation group, 32 children with phenotype identical genotypes C/T 13910 and T/T 13910, p > 0.05, presented the second group. Children from the first observation group also determined the level of expression of Gal-9 mRNA and lactose malabsorption after using exogenous lactase preparations. Results. The genotype C/C 13910 was determined in 38 (54.3 %), genotype C/T 13910 in 22 (31.4 %) and genotype T/T in 10 (14.3 %) patients. Malabsorption of lactose in children with genotype C/C 13910 averaged 32.7 ± 10.4 pmm, in children with genotypes C/T 13910 — 26.3 ± 4.9 pmm (p > 0.05) and with genotype T/T 13910 and was absent in children without obesity (p < 0.05). The average level of expression of Gal-9 mRNA in children with genotype C/C 13910 was 564.3 ± 32.8 RU DmRNA Gal-9/mRNA actin, in children with genotypes C/T and T/T 13910 — 61.04 ± 15.30 RU DmRNA Gal-9/mRNA actin, p < 0.01. It is of great importance that the children with genotype C/C 13910 and lactose malabsorption (n = 20) had the lowest average level of expression of Gal-9 mRNA (42.47 ± 13.30 RU DmRNA Gal-9/mRNA actin) whereas the children with genotype C/C 13910 and without lactose malabsorption (n =18) had the largest level (1086.73 ± 52.60 RU DmRNA Gal-9/mRNA actin), which exceeded the expression level of Gal-9 mRNA in children without obesity and lactose malabsorption (313.34 ± 19.70 RU DmRNA Gal-9 / mRNA actin), p < 0.01. After the use of exogenous lactase preparations in children with genotype C/C 13910 and lactose malabsorption for a month, the level of expression of Gal-9 mRNA approximated to the level of 246.21 ± 15.70 RU DmRNA Gal-9/mRNA actin, whereas when used only the low-lactose diet the level increased insignificantly to 58.72 ± 21.10 VD DmRNA Gal-9/mRNA actin, p < 0.01. It is also interesting that in children with genotype C/C 13910 without lactose malabsorption against the background of a low-lactose diet, the level of expression of Gal-9 mRNA decreased to 388.38 ± 20.40 RU DmRNA Gal-9/mRNA actin, approaching the level of healthy children without obesity. Conclusions. In children with genotype C/C 13910 the level of expression of Gal-9 mRNA depends on the lactose malabsorption, which requires replacement therapy that combines a low-lactose diet and the use of exogenous lactase preparations. In the absence of lactose malabsorption, using only the low-lactose diet in children with genotype C/C 13910 approximates the level of expression of Gal-9 mRNA to the level of healthy children without obesity.
galectin-9; obesity, children; lactase deficiency; lactose malabsorption
Abaturov OE, Nikulina AO. Asociation one-nucleotide polimorphism of the lactase gene in accordance with the insulin resistance of children. Suchasni medychni tehnologii'. 2016;4(31):33-36. (in Ukrainian).
Abaturov OE, Nikulina AO. Asociation one-nucleotide polimorphism of the lactase gene with dislipoproteinemia in obese children. Sovremennaya pediatriya. 2017;(2):118-121. doi: 10.15574/SP.2017.82.118. ( in Ukrainian).
Abaturov OE, Nikulina AO. Molecular-genetic concept of the formation of psychological type in children with obesity associated with lactose intolerance. Zdorovʹe rebenka. 2017;12(4):435-440. doi: 10.22141 / 2224-05126.96.36.1997.1076222. (in Ukrainian).
Abaturov OE, Nikulina AO, Logvinov DV, Colbasin PO. Diet therapy for obesity in children associated with adult lactase deficiency. Zdorovʹe rebenka. 2017;12(6):657-662; do: 10.22141 / 2224-05188.8.131.527.1128335. (in Ukrainian).
de Kivit S, Kostadinova AI, Kerperien J, et al. Galectin-9 Produced by Intestinal Epithelial Cells Enhances Aldehyde Dehydrogenase Activity in Dendritic Cells in a PI3K- and p38-Dependent Manner. J Innate Immun. 2017;9(6):609-620. doi: 10.1159/000479817.
de Kivit S, Kraneveld AD, Knippels LMJ et al. Intestinal epithelium-derived galectin-9 is involved in the immunomodulating effects of nondigestible oligosaccharides. J Innate Immun. 2013;5(6):625-38. doi: 10.1159/000350515.
Deng Y, Misselwitz B, Dai N, Fox M. Lactose Intolerance in Adults: Biological Mechanism and Dietary Management. Nutrients. 2015 Sep 18;7(9):8020-35. doi: 10.3390/nu7095380.
Han G, Chen G, Shen B, Li Y. Tim-3: an activation marker and activation limiter of innate immune cells. Front Immunol. 2013 Dec 10;4:449. doi: 10.3389/fimmu.2013.00449.
International Association for the Study of Obesity. Online database of national prevalence data from published national surveys. IASO. London. 2014.
Jacobs J, Smits E, Lardon F, Pauwels P, Deschoolmeester V. Immune Checkpoint Modulation in Colorectal Cancer: What's New and What to Expect. J Immunol Res. 2015;2015:158038. doi: 10.1155/2015/158038.
Lhuillier C, Barjon C, Niki T, et al. Impact of exogenous galectin-9 on human T cells: contribution of the T cell receptor complex to antigen-independent activation but not to apoptosis induction. J Biol Chem. 2015 Jul 3;290(27):16797-811. doi: 10.1074/jbc.M115.661272.
Liebert A, Lopez S, Jones BL, et al. World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection. Hum Genet. 2017 Nov;136(11-12):1445-1453. doi: 10.1007/s00439-017-1847-y.
Ma CJ, Li GY, Cheng YQ, et al. Cis-Association of Galectin-9 with Tim-3 Differentially Regulates IL-12/IL-23 Expressions in Monocytes via TLR Signaling. PLoS One. 2013 Aug 14;8(8):e72488. doi: 10.1371/journal.pone.0072488.
Misselwitz B, Fox M. What is normal and abnormal in lactose digestion? Lancet Gastroenterol Hepatol. 2017 Oct;2(10):696-697. doi: 10.1016/S2468-1253(17)30180-2.
Paasela M, Kolho K-L, Vaarala O, Honkanen J. Lactose inhibits regulatory T-cell-mediated suppression of effector T-cell interferon-γ and IL-17 production. Br J Nutr. 2014 Dec 14;112(11):1819-25. doi: 10.1017/S0007114514001998.
Prentice AM. Dairy products in global public health. Am J Clin Nutr. 2014 May;99(5 Suppl):1212S-6S. doi: 10.3945/ajcn.113.073437.
Ridefelt P, Hakansson LD. Lactose intolerance: Lactose tolerance test versus genotyping. Scand J Gastroenterol. 2005 Jul;40(7):822-6. doi: 10.1080/00365520510015764.
Sakuishi K, Jayaraman P, Behar SM, Anderson AC, Kuchroo VK. Emerging Tim-3 functions in antimicrobial and tumor immunity. Trends Immunol. 2011 Aug;32(8):345-9. doi: 10.1016/j.it.2011.05.003.
Styne DM, Arslanian SA, Connor EL, et al. Pediatric Obesity-Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017 Mar 1;102(3):709-757. doi: 10.1210/jc.2016-2573.
WHO. WHO European Childhood Obesity Surveillance Initiative (COSI). Geneve. 2016. Available from: http://www.euro.who.int/en/health-topics/noncommunicable-diseases/obesity/publications/2017/childhood-obesity-surveillance-initiative-cosi-protocol-october-2016
WHO. WHO: Global Action Plan for the Prevention and Control of NCDs 2013-2020. Available from: http://www.who.int/nmh/events/ncd_action_plan/en/. Accessed: 2013.
Wijnhoven TM, van Raaij JM, Spinelli A, et al. WHO European Childhood Obesity Surveillance Initiative 2008: weight, height and body mass index in 6-9-year-old children. Pediatr Obes. 2013 Apr;8(2):79-97. doi: 10.1111/j.2047-6310.2012.00090.x.