Lactose tolerance

Lactase persistence is the continued activity of the lactase enzyme in adulthood. Since lactase's only function is the digestion of lactose in milk, in most mammal species, the activity of the enzyme is dramatically reduced after weaning. In some human populations, though, lactase persistence has recently evolved as an adaptation to the consumption of nonhuman milk and dairy products beyond infancy. The majority of people around the world remain lactase nonpersistent, and consequently are affected by varying degrees of lactose intolerance as adults. However, not all genetically lactase nonpersistent individuals are noticeably lactose intolerant, and not all lactose intolerant individuals have the lactase nonpersistence genotype. Lactase persistence is the continued activity of the lactase enzyme in adulthood. Since lactase's only function is the digestion of lactose in milk, in most mammal species, the activity of the enzyme is dramatically reduced after weaning. In some human populations, though, lactase persistence has recently evolved as an adaptation to the consumption of nonhuman milk and dairy products beyond infancy. The majority of people around the world remain lactase nonpersistent, and consequently are affected by varying degrees of lactose intolerance as adults. However, not all genetically lactase nonpersistent individuals are noticeably lactose intolerant, and not all lactose intolerant individuals have the lactase nonpersistence genotype. The distribution of the lactase persistence phenotype, or the ability to digest lactose into adulthood, is not homogeneous in the world. Lactase persistence-frequencies are highly variable. In Europe, the distribution of the lactase persistence phenotype is clinal, with frequencies ranging from 15–54% in the south-east to 89–96% in the north-west. For example, only 17% of Greeks and 14% of Sardinians are predicted to possess this phenotype, while around 80% of Finns and Hungarians and 100% of Irish people are predicted to be lactase persistent. High frequencies of lactase persistence are also found in some places in Sub-Saharan Africa and in the Middle East. But the most common situation is intermediate to low lactase persistence: intermediate (11 to 32%) in Central Asia, low (<=5%) in Native Americans, East Asians, most Chinese populations and some African populations. In Africa, the distribution of lactase persistence is 'patchy': high variations of frequency are observed in neighbouring populations, for example between Beja and Nilotes from Sudan. This makes the study of lactase persistence distribution more difficult. High percentages of lactase persistence phenotype are found in traditionally pastoralist populations like Fulani and Bedouins. Lactase persistence is prevalent in Nguni and certain other pastoralist populations of South Africa as a result of the dairy they consume in their diet. Lactase persistence amongst Nguni people is, however, less common than in Northern European populations because traditionally, their consumption of dairy came primarily in the form of Amasi (known as Maas in Afrikaans), which is lower in lactose than fresh, raw milk as a result of the fermentation process it goes through. Multiple studies indicate that the presence of the two phenotypes 'lactase persistent' (derived phenotype) and 'lactase nonpersistent (hypolactasia)' is genetically programmed, and that lactase persistence is not necessarily conditioned by the consumption of lactose after the suckling period. The lactase persistent phenotype involves high mRNA expression, high lactase activity, and thus the ability to digest lactose, while the lactase nonpersistent phenotype involves low mRNA expression and low lactase activity. The enzyme lactase is encoded by the gene LCT. Hypolactasia is known to be recessively and autosomally inherited, which means that individuals with the nonpersistent phenotype are homozygous and received the two copies of a low lactase-activity allele (the ancestral allele) from their parents, who may be homozygous or at least heterozygous for the allele. Only one high-activity allele is required to be lactase persistent. Lactase persistence behaves as a dominant trait because half levels of lactase activity are sufficient to show significant digestion of lactose. Cis-acting transcriptional silence of the lactase gene is responsible for the hypolactasia phenotype. Furthermore, studies show that only eight cases were found where the parents of a child with lactase persistence were both hypolactasic. While a variety of genetic, as well as nutritional, factors determine lactase expression, no evidence has been found for adaptive alteration of lactase expression within an individual in response to changes in lactose consumption levels. The two distinct phenotypes of hypolactasia are: Phenotype I, characterized by reduced synthesis of precursor LPH, and phenotype II, associated with ample precursor synthesis, but reduced conversion of the protein to its mature molecular form.The lactase enzyme has two active sites which break down lactose. The first is at Glu1273 and the second is at Glu1749, which separately break down lactose into two separate kinds of molecules. At least six mutations (single-nucleotide polymorphisms – SNPs) have been associated with lactase expression. They are all located in a region of the gene MCM6 upstream of LCT. This region is considered as an enhancer region for the transcription of LCT. The first identified genetic variant associated with lactase persistence is C/T*−13910. The ancestral allele is C and the derived allele – associated with lactase persistence – is T. In the same study, another variant was found to also correlate with the phenotype in most of the cases: G*/A-22018.