The polymorphic expression of lactase in adults is regulated at the messenger RNA level.
OBJECTIVE
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.
Fajardo
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Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Naim
H Y
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Lacey
S W
SW
D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D015331:Cohort Studies; D004186:Disaccharidases / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006801:Humans; D007583:Jejunum / Q000737:chemistry; D043322:Lactase; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000235:genetics*
D012333:RNA, Messenger; D004186:Disaccharidases; D043322:Lactase; D001616:beta-Galactosidase