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. 1992 Feb;89(2):480–483. doi: 10.1172/JCI115609

Molecular basis of lactase levels in adult humans.

J C Escher 1, N D de Koning 1, C G van Engen 1, S Arora 1, H A Büller 1, R K Montgomery 1, R J Grand 1
PMCID: PMC442876  PMID: 1737837

Abstract

The molecular basis of adult human "lactase deficiency" has long been a subject of controversy. To address this issue, small intestinal biopsies from orienta, black, and white patients were analyzed. Adjacent samples were assayed for lactase and sucrase specific activities and the sucrase/lactase ratio (high ratio signifies lactase deficiency), and the results were compared to lactase steady-state mRNA levels detected in Northern blots probed with a human lactase mDNA. All oriental patients had high ratios and no detectable lactase mRNA. Four black patients had a similar pattern; two with low ratios had detectable mRNA. The group of white patients displayed a range of findings, from high ratio/no mRNA to low ratio/considerable mRNA. Elevated levels of lactase mRNA always correlated with the presence of elevated levels of lactase enzyme activity, suggesting that the difference in levels of adult human intestinal lactase activity among racial groups may be regulated at the level of gene transcription.

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Selected References

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  1. Boll W., Wagner P., Mantei N. Structure of the chromosomal gene and cDNAs coding for lactase-phlorizin hydrolase in humans with adult-type hypolactasia or persistence of lactase. Am J Hum Genet. 1991 May;48(5):889–902. [PMC free article] [PubMed] [Google Scholar]
  2. Büller H. A., Kothe M. J., Goldman D. A., Grubman S. A., Sasak W. V., Matsudaira P. T., Montgomery R. K., Grand R. J. Coordinate expression of lactase-phlorizin hydrolase mRNA and enzyme levels in rat intestine during development. J Biol Chem. 1990 Apr 25;265(12):6978–6983. [PubMed] [Google Scholar]
  3. Büller H. A., Van Wassenaer A. G., Raghavan S., Montgomery R. K., Sybicki M. A., Grand R. J. New insights into lactase and glycosylceramidase activities of rat lactase-phlorizin hydrolase. Am J Physiol. 1989 Oct;257(4 Pt 1):G616–G623. doi: 10.1152/ajpgi.1989.257.4.G616. [DOI] [PubMed] [Google Scholar]
  4. Castillo R. O., Reisenauer A. M., Kwong L. K., Tsuboi K. K., Quan R., Gray G. M. Intestinal lactase in the neonatal rat. Maturational changes in intracellular processing and brush-border degradation. J Biol Chem. 1990 Sep 15;265(26):15889–15893. [PubMed] [Google Scholar]
  5. DAHLQVIST A., HAMMOND J. B., CRANE R. K., DUNPHY J. V., LITTMAN A. INTESTINAL LACTASE DEFICIENCY AND LACTOSE INTOLERANCE IN ADULTS. PRELIMINARY REPORT. Gastroenterology. 1963 Oct;45:488–491. [PubMed] [Google Scholar]
  6. Flatz G. Genetics of lactose digestion in humans. Adv Hum Genet. 1987;16:1–77. doi: 10.1007/978-1-4757-0620-8_1. [DOI] [PubMed] [Google Scholar]
  7. Johnson P. F., McKnight S. L. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989;58:799–839. doi: 10.1146/annurev.bi.58.070189.004055. [DOI] [PubMed] [Google Scholar]
  8. Jonas M. M., Montgomery R. K., Grand R. J. Intestinal lactase synthesis during postnatal development in the rat. Pediatr Res. 1985 Sep;19(9):956–962. doi: 10.1203/00006450-198509000-00018. [DOI] [PubMed] [Google Scholar]
  9. Kretchmer N. Lactose and lactase--a historical perspective. Gastroenterology. 1971 Dec;61(6):805–813. [PubMed] [Google Scholar]
  10. Maiuri L., Raia V., Potter J., Swallow D., Ho M. W., Fiocca R., Finzi G., Cornaggia M., Capella C., Quaroni A. Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia. Gastroenterology. 1991 Feb;100(2):359–369. doi: 10.1016/0016-5085(91)90203-w. [DOI] [PubMed] [Google Scholar]
  11. Mantei N., Villa M., Enzler T., Wacker H., Boll W., James P., Hunziker W., Semenza G. Complete primary structure of human and rabbit lactase-phlorizin hydrolase: implications for biosynthesis, membrane anchoring and evolution of the enzyme. EMBO J. 1988 Sep;7(9):2705–2713. doi: 10.1002/j.1460-2075.1988.tb03124.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Naim H. Y., Roth J., Sterchi E. E., Lentze M., Milla P., Schmitz J., Hauri H. P. Sucrase-isomaltase deficiency in humans. Different mutations disrupt intracellular transport, processing, and function of an intestinal brush border enzyme. J Clin Invest. 1988 Aug;82(2):667–679. doi: 10.1172/JCI113646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Newcomer A. D., McGill D. B. Disaccharidase activity in the small intestine: prevalence of lactase deficiency in 100 healthy subjects. Gastroenterology. 1967 Dec;53(6):881–889. [PubMed] [Google Scholar]
  14. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  15. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Scrimshaw N. S., Murray E. B. The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance. Am J Clin Nutr. 1988 Oct;48(4 Suppl):1079–1159. doi: 10.1093/ajcn/48.4.1142. [DOI] [PubMed] [Google Scholar]
  17. Sebastio G., Villa M., Sartorio R., Guzzetta V., Poggi V., Auricchio S., Boll W., Mantei N., Semenza G. Control of lactase in human adult-type hypolactasia and in weaning rabbits and rats. Am J Hum Genet. 1989 Oct;45(4):489–497. [PMC free article] [PubMed] [Google Scholar]
  18. Sterchi E. E., Mills P. R., Fransen J. A., Hauri H. P., Lentze M. J., Naim H. Y., Ginsel L., Bond J. Biogenesis of intestinal lactase-phlorizin hydrolase in adults with lactose intolerance. Evidence for reduced biosynthesis and slowed-down maturation in enterocytes. J Clin Invest. 1990 Oct;86(4):1329–1337. doi: 10.1172/JCI114842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Welsh J. D. Isolated lactase deficiency in humans: report on 100 patients. Medicine (Baltimore) 1970 Jul;49(4):257–277. doi: 10.1097/00005792-197007000-00001. [DOI] [PubMed] [Google Scholar]
  20. Welsh J. D., Poley J. R., Bhatia M., Stevenson D. E. Intestinal disaccharidase activities in relation to age, race, and mucosal damage. Gastroenterology. 1978 Nov;75(5):847–855. [PubMed] [Google Scholar]
  21. Witte J., Lloyd M., Lorenzsonn V., Korsmo H., Olsen W. The biosynthetic basis of adult lactase deficiency. J Clin Invest. 1990 Oct;86(4):1338–1342. doi: 10.1172/JCI114843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wrischnik L. A., Higuchi R. G., Stoneking M., Erlich H. A., Arnheim N., Wilson A. C. Length mutations in human mitochondrial DNA: direct sequencing of enzymatically amplified DNA. Nucleic Acids Res. 1987 Jan 26;15(2):529–542. doi: 10.1093/nar/15.2.529. [DOI] [PMC free article] [PubMed] [Google Scholar]

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