Lactose intolerance

Lactose is the main carbohydrate present in milk. Mammalian offspring are able to digest it thanks to lactase into simpler sugars (glucose and galactose) that are easily absorbed in the intestine. There are certain genetic variants that could explain why some people find it easier to digest lactose in adulthood while others end up developing intolerance.

Lactose intolerance is one of the most common food intolerances that occurs with decreased lactase activity in the epithelium of the small intestine and is manifested when the body reacts pathologically to milk sugar. It should not be confused with cow's milk allergy, which occurs by other mechanisms involving the immune system.

Symptoms can vary markedly within and between individuals and usually appear immediately or a few hours after ingestion of milk or milk products (yogurt, cheese, cream) or other foods containing lactose (such as cakes, ice cream or chocolate). Stomach pain, nausea, diarrhea and gas are characteristic signs of lactose intolerance. The intensity of the discomfort may vary from case to case.

The ability to digest lactose is produced by the enzyme β-galactosidase called lactase-phlorizin hydrolase (LPH). The fact that in adulthood this enzyme can still be synthesized appears to be a genetic trait that follows a dominant inheritance pattern and presents a complex genetic basis, as well as being especially common in the descendants of populations that have traditionally practiced cattle domestication.

The LPH enzyme is encoded by the lactase gene (LCT), expressed in the small intestine and although the exact reason for the natural decline in lactase levels over the years is not known. Two genetic variants have been identified that are related to the expression of the LPH enzyme and that its production is not reduced in adulthood. Interestingly, these are not located within the TBI gene, but in a regulatory region called MCM6 that modulates TBI expression.

Certain variants in the MCM6 gene can lead to decreased expression of the TBI gene in intestinal cells which, over the years, can eventually lead to lactose intolerance of foods and intestinal discomfort when lactose is consumed in a certain amount.

It is important to differentiate a person with reduced LPH enzyme activity from other pathologies such as congenital lactase deficiency and secondary hypolactasia. Congenital lactase deficiency is extremely rare and appears at the onset of lactation, caused by severe mutations in both alleles of the LCT gene. On the other hand, secondary hypolactasia is caused by direct damage to the intestinal mucosa resulting in a transient reduction of lactase activity (e.g. celiac disease, Crohn's disease, viral infections and radiation/chemotherapy-induced enteritis), and has no genetic basis.

Number of observed variants

13.5 million variants

Number of variants analyzed in the study

2 variants

Bibliography

Anguita-Ruiz A., Aguilera C.M., et al. Genetics of Lactose Intolerance: An Updated Review and Online Interactive World Maps of Phenotype and Genotype Frequencies. Nutrients. 2020 Sep; 12(9): 2689.

Itan Y, Jones BL, Ingram CJ, et al. A worldwide correlation of lactase persistence phenotype and genotypes. BMC Evol Biol. 2010 Feb 9;10:36.

Lewinsky RH, Jensen TG, Møller J, et al. T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro. Hum Mol Genet. 2005 Dec 15;14(24):3945-53.

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