Lactose Malabsorption

  • C.J.E. Ingram
  • D.M. Swallow


Lactose in milk is digested and the resulting monosaccharides are absorbed in the small intestine. The surface of the small intestine has a specialised structure, composed of hundreds of ‘villi’, tiny finger-like structures that protrude from the wall of the intestine and have additional extensions called microvilli which make up the apical ‘brush border’ of the absorptive epithelial cells (enterocytes) lining the villi. This arrangement of the epithelium maximises the surface area through which the body may absorb nutrients. The enzymes, such as lactase, that facilitate digestion and absorption of carbohydrates are anchored to the surface of the brush border.


Lactose Intolerance Breath Hydrogen Fresh Milk Lactase Persistence Milk Drinking 
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  1. Anderson, B., Vullo, C. 1994. Did malaria select for primary adult lactase deficiency? Gut 35, 1487–1489.CrossRefGoogle Scholar
  2. Aoki, K. 1986. A stochastic model of gene-culture coevolution suggested by the culture-historical hypothesis. Proc. Natl. Acad. Sci. USA. 83, 2929–2933.CrossRefGoogle Scholar
  3. Arribas, J.C.D., Herrero, A.G., Martin-Lomas, M., Canada, F.J., He, S.M., Withers, S.G. 2000. Differential mechanism-based labeling and unequivocal activity assignment of the two active sites of intestinal lactase/phlorizin hydrolase. Eur. J. Biochem. 267, 6996–7005.CrossRefGoogle Scholar
  4. Auricchio, S., Rubino, A., Semenza, G., Landolt, M., Prader, A. 1963. Isolated intestinal lactase deficiency in the adult. Lancet 2, 324–326.CrossRefGoogle Scholar
  5. Bayoumi, R.A., Flatz, S.D., Kuhnau, W., Flatz, G. 1982. Beja and Nilotes: nomadic pastoralist groups in the Sudan with opposite distributions of the adult lactase phenotypes. Am. J. Phys. Anthropol. 58, 173–178.CrossRefGoogle Scholar
  6. Bayoumi, R.A., Saha, N., Salih, A.S., Bakkar, A.E., Flatz, G. 1981. Distribution of the lactase phenotypes in the population of the Democratic Republic of the Sudan. Hum. Genet. 57, 279–281.CrossRefGoogle Scholar
  7. Beck, F. 2004. The role of Cdx genes in the mammalian gut. Gut 53, 1394–1396.CrossRefGoogle Scholar
  8. Beja-Pereira, A., Luikart, G., England, P.R., Bradley, D.G., Jann, O.C., Bertorelle, G., Chamberlain, A.T., Nunes, T.P., Metodiev, S., Ferrand, N., Erhardt, G. 2003. Gene-culture coevolution between cattle milk protein genes and human lactase genes. Nat. Genet. 35, 311–313.CrossRefGoogle Scholar
  9. Bersaglieri, T., Sabeti, P.C., Patterson, N., Vanderploeg, T., Schaffner, S.F., Drake, J.A., Rhodes, M., Reich, D.E., Hirschhorn, J.N. 2004. Genetic signatures of strong recent positive selection at the lactase gene. Am. J. Hum. Genet. 74, 1111–1120.CrossRefGoogle Scholar
  10. Bloom, G., Sherman, P.W. 2005. Dairying barriers affect the distribution of lactose malabsorption. Evol. Hum. Behav. 26, 301–312.CrossRefGoogle Scholar
  11. Boll, W., Wagner, P., Mantei, N. 1991. 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. 48, 889–902.Google Scholar
  12. Bond, J.H., Levitt, M.D. 1976. Quantitative measurement of lactose absorption. Gastroenterology 70, 1058–1062.Google Scholar
  13. Bosse, T., van Wering, H.M., Gielen, M., Dowling, L.N., Fialkovich, J.J., Piaseckyj, C.M., Gonzalez, F.J., Akiyama, T.E., Montgomery, R.K., Grand, R.J., Krasinski, S.D. 2006. Hepatocyte nuclear factor-1alpha is required for expression but dispensable for histone acetylation of the lactase-phlorizin hydrolase gene in vivo. Am. J. Physiol Gastrointest. Liver Physiol. 290, 1016–1024.CrossRefGoogle Scholar
  14. Boudreau, F., Rings, E.H.H.M., van Wering, H.M., Kim, R.K., Swain, G.P., Krasinski, S.D., Moffett, J., Grand, R.J., Suh, E.R., Traber, P.G. 2002. Hepatocyte nuclear factor-1 alpha, GATA-4, and caudal related homeodomain protein Cdx2 interact functionally to modulate intestinal gene transcription – Implication for the developmental regulation of the sucrose-isomaltase gene. J. Biol. Chem. 277, 31909–31917.CrossRefGoogle Scholar
  15. Briet, F., Pochart, P., Marteau, P., Flourie, B., Arrigoni, E., Rambaud, J.C. 1997. Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect? Gut 41, 632–635.CrossRefGoogle Scholar
  16. Buller, H.A., Kothe, M.J.C., Goldman, D.A., Grubman, S.A., Sasak, W.V., Matsudaira, P.T., Montgomery, R.K., Grand, R.J. 1990. Coordinate expression of lactase-phlorizin hydrolase mRNA and enzyme levels in rat intestine during development. J. Biol. Chem. 265, 6978–6983.Google Scholar
  17. Burch, J.B. 2005. Regulation of GATA gene expression during vertebrate development. Semin. Cell Dev. Biol. 16, 71–81.CrossRefGoogle Scholar
  18. Burger, J., Kirchner, M., Bramanti, B., Haak, W., Thomas, M.G. 2007. Absence of the lactase-persistence-associated allele in early Neolithic Europeans. Proc. Natl. Acad. Sci. U.S.A. 104, 3736–3741.CrossRefGoogle Scholar
  19. Campbell, A.K., Matthews, S.B. 2005. Darwin's illness revealed. Postgrad. Med. J. 81, 248–251.CrossRefGoogle Scholar
  20. Coelho, M., Luiselli, D., Bertorelle, G., Lopes, A.I., Seixas, S., Destro-Bisol, G., Rocha, J. 2005. Microsatellite variation and evolution of human lactase persistence. Hum. Genet. 117, 329–339.CrossRefGoogle Scholar
  21. Columbo, V., Lorenz-Meyer, H., Semenza, G. 1973. Small intestinal phlorizin hydrolase: the β-glycosidase complex. Biochim. Biophys. Acta. 327, 412–424.CrossRefGoogle Scholar
  22. Cook, G.C. 1988. Human intestinal lactase and lamarckian evolution. Lancet 2, 1029.CrossRefGoogle Scholar
  23. Cook, G.C., al-Torki, M.T. 1975. High intestinal lactase concentrations in adult Arabs in Saudi Arabia. Br. Med. J. 3, 135–136.CrossRefGoogle Scholar
  24. Crittenden, R.G., Bennett, L.E. 2005. Cow's milk allergy: a complex disorder. J. Am. Coll. Nutr. 24, 582S–591S.Google Scholar
  25. Cruciani, F., Santolamazza, P., Shen, P., Macaulay, V., Moral, P., Olckers, A., Modiano, D., Holmes, S., Destro-Bisol, G., Coia, V., Wallace, D.C., Oefner, P.J., Torroni, A., Cavalli-Sforza, L.L., Scozzari, R., Underhill, P.A. 2002. A back migration from Asia to sub-Saharan Africa is supported by high-resolution analysis of human Y-chromosome haplotypes. Am. J. Hum. Genet. 70, 1197–1214.CrossRefGoogle Scholar
  26. Dahlqvist, A., Hammond, B., Crane, R., Dunphy, J., Littman, A. 1963. Intestinal lactase deficiency and lactose intolerance in adults: preliminary report. Gastroenterology 45, 488–491.Google Scholar
  27. Day, A.J., Canada, F.J., Diaz, J.C., Kroon, P.A., McLauchlan, R., Faulds, C.B., Plumb, G.W., Morgan, M.R.A., Williamson, G. 2000. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett. 468, 166–170.CrossRefGoogle Scholar
  28. Dissanyake, A.S., El-Munshid, H.A., Al-Qurain, A. 1990. Prevalence of primary adult lactose malabsorption in the eastern province of Saudi Arabia. Ann. Saudi Med. 10, 598–601.Google Scholar
  29. Enattah, N., Pekkarinen, T., Valimaki, M.J., Loyttyniemi, E., Jarvela, I. 2005a. Genetically defined adult-type hypolactasia and self-reported lactose intolerance as risk factors of osteoporosis in Finnish postmenopausal women. Eur. J. Clin. Nutr. 59, 1105–1111.CrossRefGoogle Scholar
  30. Enattah, N.S., Sulkava, R., Halonen, P., Kontula, K., Jarvela, I. 2005b. Genetic variant of lactase-persistent C/T-13910 is associated with bone fractures in very old age. J. Am. Geriatr. Soc. 53, 79–82.CrossRefGoogle Scholar
  31. Enattah, N.S., Forsblom, C., Rasinpera, H., Tuomi, T., Groop, P.H., Jarvela, I. 2004. The genetic variant of lactase persistence C (-13910) T as a risk factor for type I and II diabetes in the Finnish population. Eur. J. Clin. Nutr. 58, 1319–1322.CrossRefGoogle Scholar
  32. Enattah, N.S., Sahi, T., Savilahti, E., Terwilliger, J.D., Peltonen, L., Jarvela, I. 2002. Identification of a variant associated with adult-type hypolactasia. Nat. Genet. 30, 233–237.CrossRefGoogle Scholar
  33. Fang, R., Olds, L.C., Santiago, N.A., Sibley, E. 2001. GATA family transcription factors activate lactase gene promoter in intestinal Caco-2 cells. Am. J. Physiol Gastrointest. Liver Physiol. 280, 58–67.Google Scholar
  34. Fang, R., Santiago, N.A., Olds, L.C., Sibley, E. 2000. The homeodomain protein Cdx2 regulates lactase gene promoter activity during enterocyte differentiation. Gastroenterology 118, 115–127.CrossRefGoogle Scholar
  35. Ferguson, A., Maxwell, J. 1967. Genetic aetiology of lactose intolerance. Lancet 2, 188–190.CrossRefGoogle Scholar
  36. Fitzgerald, K., Bazar, L., Avigan, M.I. 1998. GATA-6 stimulates a cell line-specific activation element in the human lactase promoter. Am. J. Physiol. 274, 314–324.Google Scholar
  37. Flatz, G. 1984. Gene dosage effect on intestinal lactase activity demonstrated in vivo. Am. J. Hum. Genet. 36, 306–310.Google Scholar
  38. Flatz, G., Rotthauwe, H.W. 1973. Lactose nutrition and natural selection. Lancet 2, 76–77.CrossRefGoogle Scholar
  39. Freund, C.L., Wang, Q.L., Chen, S., Muskat, B.L., Wiles, C.D., Sheffield, V.C., Jacobson, S.G., McInnes, R.R., Zack, D.J., Stone, E.M. 1998. De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. Nat. Genet. 18, 311–312.CrossRefGoogle Scholar
  40. Gao, X.P., Sedgwick, T., Shi, Y.B., Evans, T. 1998. Distinct functions are implicated for the GATA-4, -5, and -6 transcription factors in the regulation of intestine epithelial cell differentiation. Mol. Cell. Biol. 18, 2901–2911.Google Scholar
  41. Gilat, T. 1971. Lactase-an adaptable enzyme? Gastroenterology 60, 346–347.Google Scholar
  42. Grunberg, J., Sterchi, E.E. 1995. Human lactase-phlorizin hydrolase: evidence of dimerization in the endoplasmic reticulum. Arch. Biochem. Biophys. 323, 367–372.CrossRefGoogle Scholar
  43. Gueguen, L., Pointillart, A. 2000. The bioavailability of dietary calcium. J. Am. Coll. Nutr. 19, 119S–136S.Google Scholar
  44. Gutierrez, I., Espinosa, A., Garcia, J., Carabano, R., De Blas, J.C. 2002. Effect of levels of starch, fiber, and lactose on digestion and growth performance of early-weaned rabbits. J. Anim. Sci. 80, 1029–1037.Google Scholar
  45. Harju, M. 2003. Chromatographic and enzymatic removal of lactose from milk. Bulletin 389, International Dairy Federation, Brussels, pp. 4–8.Google Scholar
  46. Harvey, C.B., Fox, M.F., Jeggo, P.A., Mantei, N., Povey, S., Swallow, D.M. 1993. Regional localization of the lactase-phlorizin hydrolase gene, LCT, to chromosome 2q21. Ann. Hum. Genet. 57, 179–185.CrossRefGoogle Scholar
  47. Harvey, C.B., Hollox, E.J., Poulter, M., Wang, Y., Rossi, M., Auricchio, S., Iqbal, T.H., Cooper, B.T., Barton, R., Sarner, M., Korpela, R., Swallow, D.M. 1998. Lactase haplotype frequencies in Caucasians: association with the lactase persistence/non-persistence polymorphism. Ann. Hum. Genet. 62, 215–223.CrossRefGoogle Scholar
  48. Harvey, C.B., Pratt, W., Islam, I., Whitehouse, D.B., Swallow, D.M. 1995. DNA polymorphisms in the lactase gene: linkage disequilibrium across the 70 kb region. Eur. J. Hum. Genet. 3, 27–41.Google Scholar
  49. Hauri, H.P., Sterchi, E.E., Bienz, D., Fransen, J.A., Marxer, A. 1985. Expression and intracellular transport of microvillus membrane hydrolases in human intestinal epithelial cells. J. Cell Biol. 101, 838–851.CrossRefGoogle Scholar
  50. Hertzler, S.R., Savaiano, D.A. 1996. Colonic adaptation to daily lactose feeding in lactose maldigesters reduces lactose intolerance. Am. J. Clin. Nutr. 64, 232–236.Google Scholar
  51. Hertzler, S.R., Savaiano, D.A., Levitt, M.D. 1997. Fecal hydrogen production and consumption measurements – response to daily lactose ingestion by lactose maldigesters. Dig. Dis. Sci. 42, 348–353.CrossRefGoogle Scholar
  52. Hijazi, S.S., Abulaban, A., Ammarin, Z., Flatz, G. 1983. Distribution of adult lactase phenotypes in Bedouins and in urban and agricultural populations of Jordan. Trop. Geogr. Med. 35, 157–161.Google Scholar
  53. Ho, M.W., Povey, S., Swallow, D.M. 1982. Lactase polymorphism in adult British natives: estimating allele frequencies by enzyme assays in autopsy samples. Am. J. Hum. Genet. 34, 650–657.Google Scholar
  54. Holden, C., Mace, R. 1997. Phylogenetic analysis of the evolution of lactose digestion in adults. Hum. Biol. 69, 605–628.Google Scholar
  55. Hollox, E.J., Poulter, M., Wang, Y., Krause, A., Swallow, D.M. 1999. Common polymorphism in a highly variable region upstream of the human lactase gene affects DNA–protein interactions. Eur. J. Hum. Genet. 7, 791–800.CrossRefGoogle Scholar
  56. Hollox, E.J., Poulter, M., Zvarik, M., Ferak, V., Krause, A., Jenkins, T., Saha, N., Kozlov, A.I., Swallow, D.M. 2001. Lactase haplotype diversity in the Old World. Am. J. Hum. Genet. 68, 160–172.CrossRefGoogle Scholar
  57. Ingram, C.J.E. 2008. The evolutionary genetics of lactase persistence of Africa and the Middle East. PhD Thesis, University of London, London.Google Scholar
  58. Ingram, C.J.E., Elamin, M.F., Mulcare, C.A., Weale, M.E., Tarekegn, A., Raga, T.O., Bekele, E., Elamin, F.M., Thomas, M.G., Bradman, N., Swallow, D.M. 2007. A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence? Hum. Genet. 120, 779–788.CrossRefGoogle Scholar
  59. Jacob, F., Monod, J. 1961. On regulation of gene activity. Cold Spring Harb. Symp. Quant. Biol. 26, 193–211.CrossRefGoogle Scholar
  60. Keusch, G.T., Troncale, F.J., Thavaramara, B., Prinyanont, P., Anderson, P.R., Bhamarapravathi, N. 1969. Lactase deficiency in Thailand: effect of prolonged lactose feeding. Am. J. Clin. Nutr. 22, 638–641.Google Scholar
  61. Krasinski, S.D., Upchurch, B.H., Irons, S.J., June, R.M., Mishra, K., Grand, R.J., Verhave, M. 1997. Rat lactase-phlorizin hydrolase human growth hormone transgene is expressed on small intestinal villi in transgenic mice. Gastroenterology 113, 844–855.CrossRefGoogle Scholar
  62. Krasinski, S.D., van Wering, H.M., Tannemaat, M.R., Grand, R.J. 2001. Differential activation of intestinal gene promoters: functional interactions between GATA-5 and HNF-1 alpha. Am. J. Physiol Gastrointest. Liver Physiol. 281, 69–84.Google Scholar
  63. Kruse, T.A., Bolund, L., Grzeschik, K.-H., Ropers, H.H., Sjostrom, H., Noren, O., Mantei, N., Semenza, G. 1988. The human lactase-phlorizin hydrolase gene is located on chromosome 2. FEBS Lett. 240, 123–126.CrossRefGoogle Scholar
  64. Kuokkanen, M., Kokkonen, J., Enattah, N.S., Ylisaukko-Oja, T., Komu, H., Varilo, T., Peltonen, L., Savilahti, E., Jarvela, I. 2006. Mtations in the translated region of the lactase gene (LCT) underlie congenital lactase deficiency. Am. J. Hum. Genet. 78, 339–344.CrossRefGoogle Scholar
  65. Lacey, S.W., Naim, H.Y., Magness, R.R., Gething, M.-J., Sambrook, J.F. 1994. Expression of lactase-phlorizin hydrolase in sheep is regulated at the RNA level. Biochem. J. 302, 929–935.Google Scholar
  66. Larsson, S.C., Orsini, N., Wolk, A. 2006. Milk, milk products and lactose intake and ovarian cancer risk: a meta-analysis of epidemiological studies. Int. J. Cancer. 118, 431–441.CrossRefGoogle Scholar
  67. Lee, S.Y., Wang, Z., Lin, C.K., Contag, C.H., Olds, L.C., Cooper, A.D., Sibley, E. 2002. Regulation of intestine-specific spatiotemporal expression by the rat lactase promoter. J. Biol. Chem. 277, 13099–13105.CrossRefGoogle Scholar
  68. Leese, H.J., Semenza, G. 1973. Identity between small intestinal enzymes phlorizin hydrolase and glycosylceramidase. J. Biol. Chem. 248, 8170–8173.Google Scholar
  69. Leichter, J. 1973. Effect of dietary lactose on intestinal lactase activity in young rats. J. Nutr. 103, 392–396.Google Scholar
  70. Lewinsky, R.H., Jensen, T.G., Moller, J., Stensballe, A., Olsen, J., Troelsen, J.T. 2005. T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro. Hum. Mol. Genet. 14, 3945–3953.CrossRefGoogle Scholar
  71. Lloyd, M., Mevissen, G., Fischer, M., Olsen, W., Goodspeed, D., Genini, M., Boll, W., Semenza, G., Mantei, N. 1992. Regulation of intestinal lactase in adult hypolactasia. J. Clin. Invest. 89, 524–529.CrossRefGoogle Scholar
  72. Maiuri, L., Raia, V., Potter, J., Swallow, D.M., Ho, M.W., Fiocca, R., Finzi, G., Cornaggia, M., Capella, C., Quaroni, A., Auricchio, S. 1991. Mosaic pattern of lactase expression in villous enterocytes in human adult-type hypolactasia. Gastroenterology 100, 359–369.Google Scholar
  73. Mantei, N., Villa, M., Enzler, T., Wacker, H., Boll, W., James, P., Hunziker, W., Semenza, G. 1988. Complete primary structure of human and rabbit lactase-phlorizin hydrolase: implications for biosynthesis, membrane anchoring and evolution of the enzyme. EMBO J. 7, 2705–2713.Google Scholar
  74. Matthews, S.B., Waud, J.P., Roberts, A.G., Campbell, A.K. 2005. Systemic lactose intolerance: a new perspective on an old problem. Postgrad. Med. J. 81, 167–173.CrossRefGoogle Scholar
  75. McCracken, R.D. 1971. Lactase deficiency – example of dietary evolution. Curr. Anthropol. 12, 479–517.CrossRefGoogle Scholar
  76. Meloni, G.F., Colombo, C., La, V.C., Pacifico, A., Tomasi, P., Ogana, A., Marinaro, A.M., Meloni, T. 2001. High prevalence of lactose absorbers in Northern Sardinian patients with type 1 and type 2 diabetes mellitus. Am. J. Clin. Nutr. 73, 582–585.Google Scholar
  77. Meloni, G.F., Colombo, C., La, V.C., Ruggiu, G., Mannazzu, M.C., Ambrosini, G., Cherchi, P.L. 1999. Lactose absorption in patients with ovarian cancer. Am. J. Epidemiol. 150, 183–186.CrossRefGoogle Scholar
  78. Metneki, J., Cziezel, A., Flatz, S.D., Flatz, G. 1984. A study of lactose absorption capacity in twins. Hum. Genet. 67, 296–300.CrossRefGoogle Scholar
  79. Mitchelmore, C., Troelsen, J.T., Spodsberg, N., Sjostrom, H., Noren, O. 2000. Interaction between the homeodomain proteins Cdx2 and HNF1alpha mediates expression of the lactase-phlorizin hydrolase gene. Biochem. J. 346, 529–535.CrossRefGoogle Scholar
  80. Mulcare, C.A. 2006. The Evolution of the Lactase Persistence Phenotype, PhD Thesis, University of London, London.Google Scholar
  81. Mulcare, C.A., Weale, M.E., Jones, A.L., Connell, B., Zeitlyn, D., Tarekegn, A., Swallow, D.M., Bradman, N., Thomas, M.G. 2004. The T allele of a single-nucleotide polymorphism 13.9 kb upstream of the lactase gene (LCT) (C-13.9kbT) does not predict or cause the lactase-persistence phenotype in Africans. Am. J. Hum. Genet. 74, 1102–1110.CrossRefGoogle Scholar
  82. Mutoh, H., Satoh, K., Kita, H., Sakamoto, H., Hayakawa, H., Yamamoto, H., Isoda, N., Tamada, K., Ido, K., Sugano, K. 2005. Cdx2 specifies the differentiation of morphological as well as functional absorptive enterocytes of the small intestine. Int. J. Dev. Biol. 49, 867–871.CrossRefGoogle Scholar
  83. Myles, S., Bouzekri, N., Haverfield, E., Cherkaoui, M., Dugoujon, J.M., Ward, R. 2005. Genetic evidence in support of a shared Eurasian–North African dairying origin. Hum. Genet. 117, 34–42.CrossRefGoogle Scholar
  84. Naim, H.Y., Naim, H. 1996. Dimerization of lactase-phlorizin hydrolase occurs in the endoplasmic reticulum, involves the putative membrane spanning domain and is required for an efficient transport of the enzyme to the cell surface. Eur. J. Cell Biol. 70, 198–208.Google Scholar
  85. Naim, H.Y., Sterchi, E.E., Lentze, M.J. 1987. Biosynthesis and maturation of lactase-phlorizin hydrolase in the human intestinal epithelial cells. Biochem. J. 241, 427–434.Google Scholar
  86. NIH/CEPH Collaborative Mapping Group. 1992. A comprehensive genetic linkage map of the human genome. Science 258, 67–86.CrossRefGoogle Scholar
  87. Obermayer-Pietsch, B.M., Bonelli, C.M., Walter, D.E., Kuhn, R.J., Fahrleitner-Pammer, A., Berghold, A., Goessler, W., Stepan, V., Dobnig, H., Leb, G., Renner, W. 2004. Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures. J. Bone Miner. Res. 19, 42–47.CrossRefGoogle Scholar
  88. Oesterreicher, T.J., Henning, S.J. 2004. Rapid induction of GATA transcription factors in developing mouse intestine following glucocorticoid administration. Am. J. Physiol. Gastrointest. Liver Physiol. 286, 947–953.CrossRefGoogle Scholar
  89. Olds, L.C., Sibley, E. 2003. Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element. Hum. Mol. Genet. 12, 2333–2340.CrossRefGoogle Scholar
  90. Panzer, P., Preuss, U., Joberty, G., Naim, H.Y. 1998. Protein domains implicated in intracellular transport and sorting of lactase-phlorizin hydrolase. J. Biol. Chem. 273, 13861–13869.CrossRefGoogle Scholar
  91. Pautz, W., Vogel, J. 1895. Uber die Einwirkung der Magen- und Darmschleimhaut auf einige Biosen und auf Raffinose. Z. Biol. 32, 304–307.Google Scholar
  92. Peuhkuri, K. 2000. Lactose, Lactase, and Bowel Disorders, PhD Thesis, University of Helsinki, Helsinki.Google Scholar
  93. Peuhkuri, K., Vapaatalo, H., Korpela, R., Teuri, U. 2000. Lactose intolerance – a confusing clinical diagnosis. Am. J. Clin. Nutr. 71, 600–602.Google Scholar
  94. Pie, S., Lalles, J.P., Blazy, F., Laffitte, J., Seve, B., Oswald, I.P. 2004. Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets. J. Nutr. 134, 641–647.Google Scholar
  95. Plimmer, R.H.A. 1906. On the presence of lactase in the intestines of animals and on the adaptation of the intestine to lactose. J. Physiol. 35, 20–31.Google Scholar
  96. Poulter, M., Hollox, E., Harvey, C.B., Mulcare, C.A., Peuhkuri, K., Kajander, K., Sarner, M., Korpela, R., Swallow, D.M. 2003. The causal element for the lactase persistence/non-persistence polymorphism is located in a 1 Mb region of linkage disequilibrium in Europeans. Ann. Hum. Genet. 67, 298–311.CrossRefGoogle Scholar
  97. Rasinpera, H., Savilahti, E., Enattah, N.S., Kuokkanen, M., Totterman, N., Lindahl, H., Jarvela, I., Kolho, K.L. 2004. A genetic test which can be used to diagnose adult-type hypolactasia in children. Gut 53, 1571–1576.CrossRefGoogle Scholar
  98. Rossi, M., Mauiri, L., Fusco, M.I., Salvati, V.M., Fuccio, A., Auricchio, S., Mantei, N., Zecca, L., Gloor, S.M., Semenza, G. 1997. Lactase persistence versus decline in human adults: multifactorial events are involved in downregulation after weaning. Gastroenterology 112, 1506–1514.CrossRefGoogle Scholar
  99. Sabeti, P.C., Schaffner, S.F., Fry, B., Lohmueller, J., Varilly, P., Shamovsky, O., Palma, A., Mikkelsen, T.S., Altshuler, D., Lander, E.S. 2006. Positive natural selection in the human lineage. Science 312, 1614–1620.CrossRefGoogle Scholar
  100. Sahi, T. 1974. The inheritance of selective adult-type lactose malabsorption. Scand. J. Gastroenterol. 9, 1–73.Google Scholar
  101. Saltzman, J.R., Russell, R.M., Golner, B., Barakat, S., Dallal, G.E., Goldin, B.R. 1999. A randomized trial of Lactobacillus acidophilus BG2FO4 to treat lactose intolerance. Am. J. Clin. Nutr. 69, 140–146.Google Scholar
  102. Sebastio, G., Villa, M., Sartorio, R., Guzzetta, V., Poggi, V., Auricchio, S., Boll, W., Mantei, N., Semenza, G. 1989. Control of lactase in human adult-type hypolactasia and in weaning rabbits and rats. Am. J. Hum. Genet. 45, 489–497.Google Scholar
  103. Semenza, G., Auricchio, S., Mantei, N. 1999. Small-intestinal disaccharidases. In The Metabolic and Molecular Bases of Inherited Disease, 8th edn., Vol. 1 (C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle eds.), pp. 1623–1650, McGraw-Hill, New York.Google Scholar
  104. Simoons, F.J. 1970. Primary lactose intolerance and the milking habit: a problem in biological and cultural interrelations, II. A culture historical hypothesis. Am. J. Dig. Dis. 15, 695–710.CrossRefGoogle Scholar
  105. Skovbjerg, H., Sjostrom, H., Noren, O. 1981. Purification and characterisation of amphiphilic lactase-phlorizin hydrolase from human small intestine. Eur. J. Biochem. 114, 653–661.CrossRefGoogle Scholar
  106. Snook, C.R., Mahmoud, J.N., Chang, W.P. 1976. Lactose tolerance in adult Jordanian Arabs. Trop. Geogr. Med. 28, 333–335.Google Scholar
  107. Spodsberg, N., Troelsen, J.T., Carlsson, P., Enerback, S., Sjostrom, H., Noren, O. 1999. Transcriptional regulation of pig lactase-phlorizin hydrolase. Involvement of HNF-1 and FREACs. Gastroenterology 116, 842–854.CrossRefGoogle Scholar
  108. Spurr, N.K., White, R. 1991. Report of the committee on the genetic constitution of chromosome 2. Cytogenet. Cell Genet. 58, 142–169.Google Scholar
  109. Sterchi, E., Mills, P., Fransen, J., Hauri, H., Lentze, M., Naim, H., Ginsel, L., Bond, J. 1990. Biogenesis of intestinal lactase-phlorizin hydrolase in adults with lactose intolerance. Evidence for reduced biosynthesis and slowed-down maturation in enterocytes. J. Clin. Invest. 86, 1329–1337.CrossRefGoogle Scholar
  110. Swallow, D.M., Hollox, E.J. 1999. The genetic polymorphism of intestinal lactase activity in adult humans. In The Metabolic and Molecular Bases of Inherited Disease, 8th edn., Vol. 1 (C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle eds.), pp.1651–1663, McGraw-Hill, New York.Google Scholar
  111. Thacher, T.D., Fischer, P.R., Pettifor, J.M., Lawson, J.O., Isichei, C.O., Reading, J.C., Chan, G.M. 1999. A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children. N. Engl. J. Med. 341, 563–568.CrossRefGoogle Scholar
  112. Tishkoff, S.A., Reed, F.A., Ranciaro, A., Voight, B.F., Babbitt, C.C., Silverman, J.S., Powell, K., Mortensen, H.M., Hirbo, J.B., Osman, M., Ibrahim, M., Omar, S.A., Lema, G., Nyambo, T.B., Ghori, J., Bumpstead, S., Pritchard, J.K., Wray, G.A., Deloukas, P. 2007. Convergent adaptation of human lactase persistence in Africa and Europe. Nat. Genet. 39, 31–40.CrossRefGoogle Scholar
  113. Troelsen, J., Olsen, J., Noren, O., Sjostrom, H. 1992. A novel intestinal trans factor (NF-LPH1) interacts with the lactase phlorizin hydrolase promoter and co-varies with the enzymic activity. J. Biol. Chem. 267, 20407–20411.Google Scholar
  114. Troelsen, J.T. 2005. Adult-type hypolactasia and regulation of lactase expression. Biochim. Biophys. Acta. 1723, 19–32.CrossRefGoogle Scholar
  115. Troelsen, J.T., Mehlum, A., Olsen, J., Spodsberg, N., Hansen, G.H., Prydz, H., Noren, O., Sjostrom, H. 1994. 1 Kb of the lactase-phlorizin hydrolase promoter directs post-weaning decline and small intestinal-specific expression in transgenic mice. FEBS Lett. 342, 291–296.CrossRefGoogle Scholar
  116. Troelsen, J.T., Mitchelmore, C., Spodsberg, N., Jensen, A.M., Noren, O., Sjostrom, H. 1997. Regulation of lactase-phlorizin hydrolase gene expression by the caudal-related homoeodomain protein Cdx-2. Biochem. J. 322, 833–838.Google Scholar
  117. Troelsen, J.T., Olsen, J., Moller, J., Sjostrom, H. 2003. An upstream polymorphism associated with lactase persistence has increased enhancer activity. Gastroenterology 125, 1686–1694.CrossRefGoogle Scholar
  118. van Wering, H.M., Bosse, T., Musters, A., de Jong, E., de Jong, N., Hogen Esch, C.E., Boudreau, F., Swain, G.P., Dowling, L.N., Montgomery, R.K., Grand, R.J., Krasinski, S.D. 2004. Complex regulation of the lactase-phlorizin hydrolase promoter by GATA-4. Am. J. Physiol. Gastrointest. Liver Physiol. 287, 899–909.CrossRefGoogle Scholar
  119. Vesa, T.H., Marteau, P., Korpela, R. 2000. Lactose intolerance. J. Am. Coll. Nutr. 19, 165S–175S.Google Scholar
  120. Villako, K., Maaroos, H. 1994. Clinical picture of hypolactasia and lactose intolerance. Scand. J. Gastroenterol. Suppl. 202, 36–54.CrossRefGoogle Scholar
  121. Wacker, H., Keller, P., Falchetto, R., Legler, G., Semenza, G. 1992. Location of the two catalytic sites in intestinal lactase phlorizin hydrolase: comparison with sucrase–isomaltase and other glycosidases, the membrane anchor of lactase phlorizin hydrolase. J. Biol. Chem. 267, 18744–18752.Google Scholar
  122. Wang, Y., Harvey, C.B., Pratt, W.S., Sams, V.R., Sarner, M., Rossi, M., Auricchio, S., Swallow, D.M. 1995. The lactase persistence/non-persistence polymorphism is controlled by a cis-acting element. Hum. Mol. Genet. 4, 657–662.CrossRefGoogle Scholar
  123. Wang, Z., Maravelias, C., Sibley, E. 2006. Lactase gene promoter fragments mediate differential spatial and temporal expression patterns in transgenic mice. DNA Cell Biol. 25, 215–222.CrossRefGoogle Scholar
  124. Weiskirchen, R., Tag, C.G., Mengsteab, S., Gressner, A.M., Ingram, C.J.E., Swallow, D.M. 2007. Pitfalls in LightCycler diagnosis of the single-nucleotide polymorphism 13.9 kb upstream of the lactase gene that is associated with adult-type hypolactasia. Clin. Chim. Acta 384, 93–98.CrossRefGoogle Scholar
  125. Witte, J., Lloyd, M., Lorenzsonn, V., Korsmo, H., Olsen, W. 1990. The biosynthetic basis of adult lactase deficiency. J. Clin. Invest. 86, 1338–1342.CrossRefGoogle Scholar
  126. Wright, E.M., Hirayama, B.A., Loo, D.F. 2007. Active sugar transport in health and disease. J. Intern. Med. 261, 32–43.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Genetics Evolution and EnvironmentUniversity College LondonLondonUK

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