The polymorphic expression of lactase in adults is regulated at the messenger RNA level

Gastroenterology. 1994 May;106(5):1233-41. doi: 10.1016/0016-5085(94)90014-0.


Background/aims: Lactase phlorizin hydrolase (LPH) activity is high in infants but declines 80%-90% before adulthood in most mammals, including humans. However, 95% of whites show autosomal dominant inheritance of a lifelong high lactose digesting capacity (LDC). This study attempted to clarify the molecular mechanism(s) of this phenomenon (posttranslational vs. pretranslational).

Methods: A race- and sex-balanced cohort (n = 20) was studied, and lactose tolerance and levels of jejunal lactase protein, activity, and messenger RNA (mRNA) were measured.

Results: These data confirm that black heritage predicts low LDC, and white heritage predicts high LDC. Lactase breath hydrogen and determination of lactase/sucrase ratio (L/S) from jejunal biopsy specimens divide the group by high and low LDC phenotypes concordantly. All subjects with an L/S ratio > 0.5 had immunodetectable LPH protein and measurably higher LPH mRNA levels than the remaining subjects. LPH mRNA levels are highly correlated with lactase specific activity (r = 0.80) and L/S ratio (r = 0.88).

Conclusions: The direct correlation between LPH mRNA levels and lactase expression argues that the gene responsible for the human lactase polymorphism regulates the level of LPH mRNA.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Base Sequence
  • Blotting, Western
  • Cohort Studies
  • Disaccharidases / analysis
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Gene Expression Regulation, Enzymologic / genetics*
  • Humans
  • Jejunum / chemistry
  • Lactase
  • Male
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / physiology*
  • Transcription, Genetic
  • beta-Galactosidase / genetics*


  • RNA, Messenger
  • Disaccharidases
  • Lactase
  • beta-Galactosidase