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The polymorphic expression of lactase in adults is regulated at the messenger RNA level
O Fajardo1, H Y Naim, S W Lacey
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
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.