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Genetic influences on carbohydrate digestion

Published online by Cambridge University Press:  01 November 2007

Dallas M. Swallow
Dallas M. Swallow*
Affiliation:
Galton Laboratory, Department of Biology, Wolfson House, 4 Stephenson Way, London NW1 2HE, UK
*
*Corresponding author: Dr D. M. Swallow, fax +44 207387 3496, email dswallow@hgmp.mrc.ac.uk
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Abstract

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The diversity of the human genome leads to many functional differences between individuals. The present review focuses on genetic variations, both rare and common, that are of relevance to digestion of the sugars and starches that form a major part of human diets, and considers these in relation to the evolution of our species. For example, intolerances of dietary saccharides are not usually life-threatening because symptoms can be avoided by removal of the offending sugar from the diet, and deficiencies of the relevant enzymes are in some cases found at relatively high frequencies in certain populations. This is of evolutionary interest in relation to changes in the human diet, and the lactase-persistence polymorphism, in particular, provides an interesting model. More of the world's adult population are lactase-deficient than have high lactase. The other deficiencies are however much more rare, but the significance of variant alleles at these loci, and also heterozygosity for deficiency alleles, to human nutrition and health is an area that is relatively unexplored.

Keywords

Carbohydrate digestionLactase deficiencyFood intoleranceHuman genetic variation
Type
Research Article
Information
Nutrition Research Reviews , Volume 16 , Issue 1 , June 2003 , pp. 37 - 43
Copyright
Copyright © CABI Publishing 2003

References

Ali, M, Rellos, P & Cox, TM (1998) Hereditary fructose intolerance. Journal of Medical Genetics 35, 353–365.CrossRefGoogle ScholarPubMed
Anderson, B & Vullo, C (1994) Did malaria select for primary adult lactase deficiency? Gut 35, 1487–1489.CrossRefGoogle ScholarPubMed
Armada, LJ, Mackey, AD & Gregory, JF III (2002) Intestinal brush border membrane catalyzes hydrolysis of pyridoxine-5′-beta- D-glucoside and exhibits parallel developmental changes of hydrolytic activities toward pyridoxine-5′-beta-D-glucoside and lactose in rats. Journal of Nutrition 132, 2695–2699.CrossRefGoogle ScholarPubMed
Arribas, JC, Herrero, AG, Martin-Lomas, M, Canada, FJ, He, S & Withers, SG (2000) Differential mechanism-based labeling and unequivocal activity assignment of the two active sites of intestinal lactase/phlorizin hydrolase. European Journal of Biochemistry 267, 6996–7005.CrossRefGoogle ScholarPubMed
Asp, NG, Berg, NO, Dahlqvist, A, Gudmand-Hoyer, E, Jarnum, S & McNair, A (1975) Intestinal disaccharidases in Greenland Eskimos. Scandinavian Journal of Gastroenterology 10, 513–519.CrossRefGoogle ScholarPubMed
Auricchio, S (1998) Lactase deficiency phenotype has not been selected by malaria. Italian Journal of Gastroenterology and Hepatology 30, 494–495.Google Scholar
Bell, RR, Draper, HH & Bergan, JG (1973) Sucrose, lactose, and glucose tolerance in northern Alaskan Eskimos. American Journal of Clinical Nutrition 26, 1185–1190.CrossRefGoogle ScholarPubMed
Bentley, DR (2000) The Human Genome Project – an overview. Medical Research Reviews 20, 189–196.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Birlouez-Aragon, I, Ravelontseheno, L, Villate-Cathelineau, B, Cathelineau, G & Abitbol, G (1993) Disturbed galactose metabolism in elderly and diabetic humans is associated with cataract formation. Journal of Nutrition 123, 1370–1376.Google ScholarPubMed
Calvo, JH, Lopez-Corrales, NL, Osta, R, Skinner, TM, Anderson, SI, Rodellar, C, Zaragoza, P & Archibald, AL (2000) Assignment of maltase glucoamylase (MGAM) to pig chromosome 2 (2q21) by fluorescence in situ hybridization and confirmation by genetic mapping. Cytogenetics and Cell Genetics 90, 236–237.CrossRefGoogle ScholarPubMed
Chantret, I, Lacasa, M, Chevalier, G, Ruf, J, Islam, I, Mantei, N, Edwards, Y, Swallow, D & Rousset, M (1992) Sequence of the complete cDNA and the 5′ structure of the human sucrase-isomaltase gene. Possible homology with a yeast glucoamylase. Biochemical Journal 285, 915–923.CrossRefGoogle ScholarPubMed
Day, AJ, Canada, FJ, Diaz, JC, Kroon, PA, McLauchlan, R, Faulds, CB, Plumb, GW, Morgan, MR & Williamson, G (2000) Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Letters 468, 166–170.CrossRefGoogle ScholarPubMed
Ellestad-Sayed, JJ, Haworth, JC & Hildes, JA (1978) Disaccharide malabsorption and dietary patterns in two Canadian Eskimo communities. American Journal of Clinical Nutrition 31, 1473–1478.CrossRefGoogle ScholarPubMed
Enattah, NS, Sahi, T, Savilahti, E, Terwilliger, JD, Peltonen, L & Jarvela, II (2002) Identification of a variant associated with adult-type hypolactasia. Nature Genetics 30, 233–237.CrossRefGoogle ScholarPubMed
Groot, PC, Bleeker, MJ, Pronk, JC, Arwert, F, Mager, WH, Planta, RJ, Eriksson, AW & Frants, RR (1989) The human alpha-amylase multigene family consists of haplotypes with variable numbers of genes. Genomics 5, 29–42.CrossRefGoogle ScholarPubMed
Groot, PC, Mager, WH & Frants, RR (1991) Interpretation of polymorphic DNA patterns in the human alpha-amylase multigene family. Genomics 10, 779–785.CrossRefGoogle ScholarPubMed
Gudmand-Hoyer, E & Skovbjerg, H (1996) Disaccharide digestion and maldigestion. Scandinavian Journal of Gastroenterology 216, Suppl., 111–121.CrossRefGoogle ScholarPubMed
Harris, H (1971) Polymorphism and protein evolution. The neutral mutation-random drift hypothesis. Journal of Medical Genetics 8, 444–452.CrossRefGoogle ScholarPubMed
Hollox, EJ, Poulter, M, Wang, Y, Krause, A & Swallow, DM (1999) Common polymorphism in a highly variable region upstream of the human lactase gene affects DNA-protein interactions. European Journal of Human Genetics 7, 791–800.CrossRefGoogle Scholar
Hollox, EJ, Poulter, M, Zvarik, M, Ferak, V, Krause, A, Jenkins, T, Saha, N, Kozlov, AI & Swallow, DM (2001) Lactase haplotype diversity in the Old World. American Journal of Human Genetics 68, 160–172.CrossRefGoogle ScholarPubMed
Ishihara, R, Taketani, S, Sasai-Takedatsu, M, Kino, M, Tokunaga, R & Kobayashi, Y (1997) Molecular cloning, sequencing and expression of cDNA encoding human trehalase. Gene 202, 69–74.CrossRefGoogle ScholarPubMed
Jacob, R, Zimmer, KP, Schmitz, J & Naim, HY (2000) Congenital sucrase-isomaltase deficiency arising from cleavage and secretion of a mutant form of the enzyme. Journal of Clinical Investigation 106, 281–287.CrossRefGoogle ScholarPubMed
Jarvela, I, Sabri Enattah, N, Kokkonen, J, Varilo, T, Savilahti, E & Peltonen, L (1998) Assignment of the locus for congenital lactase deficiency to 2q21, in the vicinity of but separate from the lactase-phlorizin hydrolase gene. American Journal of Human Genetics 63, 1078–1085.CrossRefGoogle ScholarPubMed
Jost, B, Duluc, I, Richardson, M, Lathe, R & Freund, JN (1997) Functional diversity and interactions between the repeat domains of rat intestinal lactase. Biochemical Journal 327, 95–103.CrossRefGoogle ScholarPubMed
Levin, RJ (1994) Digestion and absorption of carbohydrates – from molecules and membranes to humans. American Journal of Clinical Nutrition 59, 690S–698S.CrossRefGoogle ScholarPubMed
Mackey, AD, Henderson, GN & Gregory, JF III (2002) Enzymatic hydrolysis of pyridoxine-5′-beta-D-glucoside is catalyzed by intestinal lactase-phlorizin hydrolase. Journal of Biological Chemistry 277, 26858–26864.CrossRefGoogle ScholarPubMed
McNair, A, Gudmand-Hoyer, E, Jarnum, S & Orrild, L (1972) Sucrose malabsorption in Greenland. British Medical Journal 2, 19–21.CrossRefGoogle ScholarPubMed
Madzarovova-Nohejlova, J (1973) Trehalase deficiency in a family. Gastroenterology 65, 130–133.CrossRefGoogle ScholarPubMed
Meier, RJ, Draper, H & Milan, F (1991) Pedigree analysis of sucrose intolerance among Native Alaskans. Arctic Medical Research 50, 8–12.Google ScholarPubMed
Meloni, T, Colombo, C, Ogana, A, Mannazzu, MC & Meloni, GF (1996) Lactose absorption in patients with glucose 6-phosphate dehydrogenase deficiency with and without favism. Gut 39, 210–213.CrossRefGoogle ScholarPubMed
Meloni, T, Colombo, C, Ruggiu, G, Dessena, M & Meloni, GF (1998) Primary lactase deficiency and past malarial endemicity in Sardinia. Italian Journal of Gastroenterology and Hepatology 30, 490–493.Google ScholarPubMed
Nichols, BL, Avery, SE, Karnsakul, W, Jahoor, F, Sen, P, Swallow, DM, Luginbuehl, U, Hahn, D & Sterchi, EE (2002) Congenital maltase-glucoamylase deficiency associated with lactase and sucrase deficiencies. Journal of Pediatric and Gastroenterological Nutrition 35, 573–579.Google ScholarPubMed
Nichols, BL, Avery, S, Sen, P, Swallow, DM, Hahn, D & Sterchi, E (2003) The maltase–glucoamylase gene: Common ancestry to sucrase–isomaltase with complementary starch digestion activities. Proceedings of the National Academy of Sciences 100, 1432–1437.CrossRefGoogle ScholarPubMed
Nichols, BL, Eldering, J, Avery, S, Hahn, D, Quaroni, A & Sterchi, E (1998) Human small intestinal maltase-glucoamylase cDNA cloning. Homology to sucrase-isomaltase. Journal of Biological Chemistry 273, 3076–3081.CrossRefGoogle ScholarPubMed
Nishide, T, Nakamura, Y, Emi, M, Yamamoto, T, Ogawa, M, Mori, T & Matsubara, K (1986) Primary structure of human salivary alpha-amylase gene. Gene 41, 299–304.Google ScholarPubMed
Oesterreicher, TJ, Markesich, DC & Henning, SJ (2001) Cloning, characterization and mapping of the mouse trehalase (Treh) gene. Gene 270, 211–220.CrossRefGoogle ScholarPubMed
Ouwendijk, J, Peters, WJ, te Morsche, RH, van de Vorstenbosch, RA, Ginsel, LA, Naim, HY & Fransen, JA (1998) Analysis of a naturally occurring mutation in sucrase-isomaltase: glutamine 1098 is not essential for transport to the surface of COS-1 cells. Biochimica et Biophysica Acta 1406, 299–306.CrossRefGoogle ScholarPubMed
Poulter, M, Hollox, E, Harvey, CB, Mulcare, CM, Peuhkuri, K, Kajander, K, Sarner, M, Korpela, R & Swallow, DM (2003) The causal element for the lactose persistence/non-persistence polymorphism is located in a 1 Mb region of linkage disequilibrium in Europeans. Annals of Human Geretics 67, (In the Press)Google Scholar
Quezada-Calvillo, R, Rodriguez-Zuniga, F & Underdown, BJ (2002) Partial characterization of murine intestinal maltase-glucoamylase. Biochemical and Biophysical Research Communications 295, 394–400.CrossRefGoogle ScholarPubMed
Ringrose, RE, Preiser, H & Welsh, JD (1979) Sucrase-isomaltase (Palatinase) deficiency diagnosed during adulthood. Digestive Diseases and Sciences 25, 384–387.CrossRefGoogle Scholar
Rossi, M, Maiuri, L, Fusco, MI, Salvati, VM, Fuccio, A, Auricchio, S, Mantei, N, Zecca, L, Gloor, SM & Semenza, G (1997) Lactase persistence versus decline in human adults: multifactorial events are involved in down-regulation after weaning. Gastroenterology 112, 1506–1514.CrossRefGoogle ScholarPubMed
Ruf, J, Wacker, H, James, P, Maffia, M, Seiler, P, Galand, G, von Kieckebusch, A, Semenza, G & Mantei, N (1990) Rabbit small intestinal trehalase. Purification, cDNA cloning, expression, and verification of glycosylphosphatidylinositol anchoring. Journal of Biological Chemistry 265, 15034–15039.CrossRefGoogle ScholarPubMed
Savilahti, E, Launiala, K & Kuitunen, P (1983) Congenital lactase deficiency. A clinical study on 16 patients. Archives of Disease in Childhood 58, 246–252.CrossRefGoogle ScholarPubMed
Seely, S (2000) Possible connection between milk and coronary heart disease: the calcium hypothesis. Medical Hypotheses 54, 701–703.CrossRefGoogle ScholarPubMed
Semenza, G, Auricchio, S & Mantei, N (2000) Small intestinal disaccharidases. In The Metabolic and Molecular Basis of Inherited Disease, vol.1, chapter 75, pp. 1601–1650 [Scriver, CR, Beaudet, AL, Sly, WS and Valle, D editors]. New York: McGraw-Hill.Google Scholar
Shirazi-Beechey, SP, Kemp, RB, Dyer, J & Beechey, RB (1989) Changes in the functions of the intestinal brush border membrane during the development of the ruminant habit in lambs. Comparative Biochemistry and Physiology 94, 801–806.Google ScholarPubMed
Spodsberg, N, Jacob, R, Alfalah, M, Zimmer, KP & Naim, HY (2001) Molecular basis of aberrant apical protein transport in an intestinal enzyme disorder. Journal of Biological Chemistry 276, 23506–23510.CrossRefGoogle Scholar
Swallow, DM & Hollox, EJ (2000) The genetic polymorphism of intestinal lactase activity in adult humans. In The Metabolic and Molecular Basis of Inherited Disease, pp. 1651–1662, chapter 76 [Scriver, CR, Beaudet, AL, Sly, WS and Valle, D editors]. New York: McGraw-Hill.Google Scholar
Treem, WR (1996) Clinical heterogeneity in congenital sucrase-isomaltase deficiency. Journal of Pediatrics 128, 727–729.Google ScholarPubMed
Veitch, AM, Kelly, P, Segal, I, Soies, SK & Farthing, MJ (1998) Does sucrase deficiency in black South Africans protect against colonic disease? Lancet 351, 183.CrossRefGoogle ScholarPubMed
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 with other glycosidases, the membrane anchor of lactase-phlorizin hydrolase. Journal of Biological Chemistry 267, 18744–18752.CrossRefGoogle ScholarPubMed
Wang, Y, Harvey, CB, Hollox, EJ, Phillips, AD, Poulter, M, Clay, P, Walker-Smith, JA & Swallow, DM (1998) The genetically programmed down-regulation of lactase in children. Gastroenterology 114, 1230–1236.CrossRefGoogle ScholarPubMed
Wang, Y, Harvey, CB, Pratt, WS, Sams, VR, Sarner, M, Rossi, M, Auricchio, S & Swallow, DM (1995) The lactase persistence/non-persistence polymorphism is controlled by a cis-acting element. Human and Molecular Genetics 4, 657–662.CrossRefGoogle ScholarPubMed
Wasserman, D, Hoekstra, JH, Tolia, V, Taylor, CJ, Kirschner, BS, Takeda, J, Bell, GI, Taub, R & Rand, EB (1996) Molecular analysis of the fructose transporter gene (GLUT5) in isolated fructose malabsorption. Journal of Clinical Investigation 98, 2398–2402.CrossRefGoogle ScholarPubMed
Weiss, SL, Lee, EA & Diamond, J (1998) Evolutionary matches of enzyme and transporter capacities to dietary substrate loads in the intestinal brush border. Proceedings of the National Academy of Sciences, USA 95, 2117–2121.CrossRefGoogle ScholarPubMed
Wright, E, Martin, GM & Turk, E (2000) Familial glucose-galactose malabsorption and hereditary renal glycosuria. In The Metabolic and Molecular Basis of Inherited Disease, vol. 3, chapter 190, pp. 4891–4908 [Scriver, CR, Beaudet, AL, Sly, WS and Valle, D editors]. New York: McGraw-Hill.Google Scholar
Yokouchi, H, Horii, A, Emi, M, Tomita, N, Doi, S, Ogawa, M, Mori, T & Matsubara, K (1990) Cloning and characterization of a third type of human alpha-amylase gene, AMY2B. Gene 90, 281–286.CrossRefGoogle ScholarPubMed
Zecca, L, Mesonero, JE, Stutz, A, Poiree, JC, Giudicelli, J, Cursio, R, Gloor, SM & Semenza, G (1998) Intestinal lactase-phlorizin hydrolase (LPH): the two catalytic sites; the role of the pancreas in pro-LPH maturation. FEBS Letters 435, 225–228.CrossRefGoogle ScholarPubMed