The genetically programmed down-regulation of lactase in children

Background & Aims: Intestinal lactase activity is high in all healthy human babies, but in adults a genetic polymorphism, which acts in cis to the lactase gene, determines high or low messenger RNA (mRNA) expression and activity (lactase persistence and nonpersistence, respectively). Our aim was to investigate the onset of expression of this polymorphism in children. Methods: Activities were analyzed in relation to age in normal biopsy specimens from a 20-year collection of diagnostic specimens. In a smaller set of 32 samples, aged 2–132 months, RNA was extracted for semiquantitative reverse-transcription polymerase chain reaction. Marker polymorphisms were used to determine the allelic origin of lactase mRNA transcripts. Results: Analysis of 866 children showed evidence that the lactase persistence/nonpersistence polymorphism began before 5 years of age. The 32 children tested had high lactase mRNA and activity. Six children aged 2–16 months showed equal expression of two alleles, 2 children aged 7 and 14 months showed slightly asymmetric expression, and 7 children aged 22–132 months showed very asymmetric expression, the second allele being undetectable in the 11-year-old, as previously seen in lactase-persistent heterozygote adults. Conclusions: Genetically programmed down-regulation of the lactase gene is detectable in children from the second year of life, although the onset and extent are somewhat variable. GASTROENTEROLOGY 1998;114:1230-1236