Genetics of Lactase Persistence and Lactose Intolerance

Abstract

The enzyme lactase that is located in the villus enterocytes of the small intestine is responsible for digestion of lactose in milk. Lactase activity is high and vital during infancy, but in most mammals, including most humans, lactase activity declines after the weaning phase. In other healthy humans, lactase activity persists at a high level throughout adult life, enabling them to digest lactose as adults. This dominantly inherited genetic trait is known as lactase persistence. The distribution of these different lactase phenotypes in human populations is highly variable and is controlled by a polymorphic element cis-acting to the lactase gene. A putative causal nucleotide change has been identified and occurs on the background of a very extended haplotype that is frequent in Northern Europeans, where lactase persistence is frequent. This single nucleotide polymorphism is located 14 kb upstream from the start of transcription of lactase in an intron of the adjacent gene MCM6. This change does not, however, explain all the variation in lactase expression.

Milk Consumption is Not Affected by C/T-13910 Single Nucleotide Polymorphism in a Tajik Population in a Southern Region of Uzbekistan

“…However, not all individuals with a lactase non-persistence genotype have expressed lactose intolerance and not all the people who are intolerant to lactose are carriers of lactase non-persistence alleles [1,4,25].…”

“…It is one of the most common enzyme deficiencies among mammals, and has a homozygous recessive inheritance trait [2,3]. Most of the adult human populations have high prevalence of hypolactasia and intolerance to milk [4]. The activity of lactase in the intestinal mucosa progressively decreases after the weaning period [5,6].…”

Zinc–gene interaction related to inflammatory/immune response in ageing

“…For each nutrient, there is a window of intake between the Recommended Dietary Allowance (RDA), (which is defined as the dietary intake sufficient to meet the requirement of 97% of healthy individuals in a particular stage of life and sex group), and the tolerable upper limit (UL), which is the highest nutrient intake that can be achieved without incurring risk of adverse health effects for most individuals in the general population [140]. Although worldwide research on genetic variation that requires a different RDA or UL is still in progress, several genes and alleles have been suggested to affect nutrient utilization, including genes involved in the metabolism of folate and vitamin B-12 [60,62,91], lipids [61,74] alcohol [20], lactose [142], iron [46,77] and zinc [31,97]. In the context of healthy lifespan and longevity, nutrigenetic and nutrigenomic implications around this last nutrient (zinc) appear very important taking into account that: (1) RDA (11 mg/day for men and 8 mg/day for women) and UL (40 mg/day for adults) for zinc are very close [50]; (2) About 10% of the human proteome consists in potential Znbinding proteins [5]; (3) Proteins devoted to Zn transport (ZnT) and buffering, most of which display functional polymorphic sites, include at least ten members of the ZnT family [134], 15 members of the ZIP family (i.e.…”

The Reluctant Calf

“…6,8 This is somewhat strange because the C/T variant site is in a noncoding intron of another gene with no known relationship to lactase. Yet this T allele is associated with lower LCT production; 9 generally, people carrying even a single copy of the T allele produce enough lactase as adults to give them near-"normal" milk tolerance.…”