Abstract

Lactose malabsorption occurs when the milk sugar, lactose, is not hydrolysed and absorbed in the small intestine, usually because of reduced levels of lactase, an intestinal specific β-galactosidase (EC 3.2.1.108), otherwise known as lactase–phlorizin hydrolase (LPH, because of its additional activities). Instead, the lactose is digested by bacteria in the colon, and this can cause symptoms of lactose intolerance. In humans, the persistence of lactase in adults is a genetically controlled polymorphic trait that varies in frequency between populations. Several single-nucleotide variants that associate with lactase persistence occur upstream of the lactase gene (LCT). One variant (–13910*T) predominates in Europe, and the others (–13907*G, –13915*G, –14010*C, –14009*G) have distinct geographical distributions. These variants are thought to allow LCT to escape developmentally programmed down-regulation. Evidence from geographic distributions, lifestyle association and molecular genetics indicates that lactase persistence has been very advantageous in some populations, although the specific selective advantage is uncertain and is likely to vary between populations. In individuals who cannot digest lactose, symptoms of lactose intolerance (note that this is distinct from immunological intolerance to other components of milk) can be avoided by consuming smaller quantities of milk or reduced lactose products such as yoghurts and cheese. Whilst genetic testing of –13910*T in Europeans with irritable bowel syndrome may aid differential diagnosis, this test cannot be considered useful in other populations or in individuals of mixed ancestry.