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Changing genes; losing lactase
  1. R J Grand1,
  2. R K Montgomery1,
  3. D K Chitkara1,
  4. J N Hirschhorn2
  1. 1Divisions of Gastroenterology and Nutrition, Children’s Hospital Boston, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
  2. 2Department of Genetics, Children’s Hospital Boston, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
  1. Correspondence to:
    Dr R J Grand, Harvard Medical School, Division of Gastroenterology and Nutrition, The Children’s Hospital, 300 Longwood Avenue, Hunnewell G, Boston, MA 02115, USA;

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Transcriptional regulation of the lactase-phlorizin hydrolase (LPH) gene by polymorphisms is associated with persistence of high levels of intestinal lactase activity or non-persistence

Lactase-phlorizin hydrolase (LPH), an intestinal microvillus membrane enzyme that hydrolyses lactose, is a critical enzyme for neonatal nutrition. The developmental pattern of lactase expression in the human fetus is distinct from that of similar digestive enzymes. Before week 24 of gestation, intestinal lactase activity is low. It then begins to increase, and during the third trimester lactase activity increases markedly until levels in term neonates are at or above those of infants aged 2–11 months.1 Lactase exhibits a characteristic proximal to distal pattern of expression in the small intestine; enzyme activity is greatest in the mid- jejunum, with decreasing activity both proximally and distally, resulting in minimal activity in the proximal duodenum and the terminal ileum.2

In most human populations, lactase activity decreases during mid-childhood (about five years of age), resulting in low levels from that age onwards. This pattern is similar to that seen in all other mammals examined, with a reduction in intestinal lactase activity at weaning to a fraction of that found in the suckling newborn. In striking contrast, a minority of the human population, especially people of Northern European extraction and a few other racial groups, retain high levels of activity throughout adult life.3 Persistence of elevated lactase activity is thought to be a relatively recent human evolutionary development, arising within the last 10 000 years, coincident with the development of dairying.4 A small number of subjects with lactase non-persistence have been demonstrated to have an abnormality in the intracellular processing of newly synthesised LPH protein, indicating post-transcriptional control of non-persistence.5 However, it is now clear that in humans, as in all mammals studied, the primary mechanism of …

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