title: Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function.
abstract: New evidence for the regulation of vitamin C homeostasis has emerged from several studies of human genetic variation. Polymorphisms in the genes encoding sodium-dependent vitamin C transport proteins are strongly associated with plasma ascorbate levels and likely impact tissue cellular vitamin C status. Furthermore, genetic variants of proteins that suppress oxidative stress or detoxify oxidatively damaged biomolecules, i.e., haptoglobin, glutathione-S-transferases, and possibly manganese superoxide dismutase, affect ascorbate levels in the human body. There also is limited evidence for a role of glucose transport proteins. In this review, we examine the extent of the variation in these genes, their impact on vitamin C status, and their potential role in altering chronic disease risk. We conclude that future epidemiological studies should take into account genetic variation in order to successfully determine the role of vitamin C nutriture or supplementation in human vitamin C status and chronic disease risk.
authors: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. michelsa@onid.orst.edu
authors: Alexander J
authors: AJ
authors: Michels
authors: Tory M
authors: TM
authors: Hagen
authors: Balz
authors: B
authors: Frei
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport; D014644:Genetic Variation; D006706:Homeostasis; D006801:Humans; D010088:Oxidoreductases / Q000378:metabolism*; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics* / Q000378:metabolism
chemical_list: D060347:Sodium-Coupled Vitamin C Transporters; D010088:Oxidoreductases; D001205:Ascorbic Acid
references: Environ Int. 2012 Sep 15;45:1-8
references: 22565211
references: Curr Diab Rep. 2012 Jun;12(3):274-9
references: 22427005
references: Am J Physiol Cell Physiol. 2009 Nov;297(5):C1220-7
references: 19741195
references: Genomics. 1992 Nov;14(3):823-5
references: 1427917
references: Am J Clin Nutr. 1999 Jun;69(6):1086-107
references: 10357726
references: Biochem J. 2011 Nov 15;440(1):73-84
references: 21770893
references: J Clin Invest. 2010 Apr;120(4):1069-83
references: 20200446
references: J Clin Pathol. 2004 Oct;57(10):1094-5
references: 15452167
references: Br J Nutr. 2009 Dec;102 Suppl 1:S10-37
references: 20100364
references: Biochim Biophys Acta. 1999 Nov 9;1461(1):1-9
references: 10556483
references: Epidemiology. 2012 Jul;23(4):607-15
references: 22531667
references: Nat Med. 2002 May;8(5):514-7
references: 11984597
references: Carcinogenesis. 2006 Nov;27(11):2250-7
references: 16774936
references: Annu Rev Pharmacol Toxicol. 2005;45:51-88
references: 15822171
references: Am J Clin Nutr. 2010 May;91(5):1220-6
references: 20335546
references: Am J Clin Nutr. 2009 Nov;90(5):1411-7
references: 19710200
references: Am J Clin Nutr. 1997 Sep;66(3):606-10
references: 9280180
references: J Biol Chem. 2000 Sep 8;275(36):28246-53
references: 10862609
references: Am J Hum Genet. 2012 Jun 8;90(6):1046-63
references: 22658545
references: Chem Res Toxicol. 2010 Jan;23(1):37-47
references: 20043646
references: Am J Clin Nutr. 2008 Jan;87(1):64-9
references: 18175738
references: PLoS One. 2007 Apr 11;2(4):e362
references: 17426810
references: Basic Clin Pharmacol Toxicol. 2009 Jun;104(6):419-33
references: 19489786
references: Nutr Cancer. 2008;60(5):652-9
references: 18791929
references: Br J Nutr. 2011 Dec;106(12):1814-25
references: 21733302
references: Eur J Nutr. 2011 Sep;50(6):437-46
references: 21152927
references: Am J Clin Nutr. 2010 Dec;92(6):1494-500
references: 20926521
references: Nature. 1999 May 6;399(6731):70-5
references: 10331392
references: J Biol Chem. 2012 Feb 3;287(6):3860-72
references: 22041898
references: Am J Epidemiol. 2006 Feb 1;163(3):245-54
references: 16357110
references: BMJ. 1995 Jun 17;310(6994):1563-6
references: 7787644
references: AIDS. 1998 Jun 18;12(9):1027-32
references: 9662199
references: Hum Genet. 2004 Sep;115(4):285-94
references: 15316768
references: Eur J Cancer. 2009 Jul;45(10):1824-30
references: 19243932
references: Biochem Biophys Res Commun. 2007 Sep 21;361(2):385-90
references: 17643393
references: Clin Biochem. 2010 Sep;43(13-14):1118-23
references: 20627099
references: Oncogene. 2011 Feb 17;30(7):843-53
references: 20935678
references: Br J Nutr. 2012 Mar;107(6):928-33
references: 21896242
references: Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3704-9
references: 8623000
references: Lancet. 2001 Mar 3;357(9257):657-63
references: 11247548
references: Am J Clin Nutr. 2011 Sep;94(3):929-37
references: 21813807
references: Ophthalmology. 2011 Oct;118(10):1958-1965.e2
references: 21705085
references: PLoS One. 2012;7(8):e42542
references: 22880027
references: Am J Clin Nutr. 2010 Aug;92(2):375-82
references: 20519558
references: Biochim Biophys Acta. 2005 Dec 30;1732(1-3):76-81
references: 16380174
references: J Bioenerg Biomembr. 1994 Aug;26(4):359-67
references: 7844110
references: Free Radic Biol Med. 2011 May 1;50(9):1196-209
references: 21335086
references: Antioxid Redox Signal. 2010 Feb;12(2):209-17
references: 19769483
references: Clin Chim Acta. 2006 Mar;365(1-2):319-24
references: 16256097
references: J Nutr. 2002 Jun;132(6):1299-306
references: 12042450
references: Antioxid Redox Signal. 2010 Feb;12(2):293-304
references: 19659435
references: Neurology. 2003 Nov 11;61(9):1273-5
references: 14610137
references: Food Chem Toxicol. 2007 Dec;45(12):2592-6
references: 17706336
references: Am J Clin Nutr. 2002 Feb;75(2):321-5
references: 11815325
references: Biochem Biophys Res Commun. 2005 Aug 19;334(1):150-6
references: 15993839
references: J Invest Dermatol. 2007 Mar;127(3):698-706
references: 17008880
references: Chem Res Toxicol. 2009 May;22(5):863-74
references: 19326901
references: Biochem Biophys Res Commun. 2011 Nov 4;414(4):737-42
references: 22001929
references: Cancer Cell. 2007 Sep;12(3):230-8
references: 17785204
references: Ann Neurol. 1998 Aug;44(2):286-7
references: 9708557
references: Atherosclerosis. 1999 Aug;145(2):287-92
references: 10488955
references: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9842-6
references: 11504949
references: PLoS One. 2008 Jun 30;3(7):e2816
references: 18636124
references: Neurochem Res. 1999 Apr;24(4):587-94
references: 10227690
references: Nature. 1993 Jul 1;364(6432):79-82
references: 8316303
references: Biochem Biophys Res Commun. 2007 Aug 17;360(1):295-8
references: 17586466
references: Oncogene. 2006 Mar 13;25(11):1639-48
references: 16550164
references: Pharmacol Res. 2012 Jul;66(1):1-6
references: 22465143
references: Am J Respir Crit Care Med. 2008 Jul 1;178(1):13-9
references: 18420959
references: Biochem Biophys Res Commun. 1999 Sep 7;262(3):762-8
references: 10471399
references: J Mol Biol. 2012 Jul 13;420(3):190-203
references: 22522127
references: J Biol Chem. 1997 Jul 25;272(30):18982-9
references: 9228080
references: Hum Mol Genet. 2010 Oct 1;19(19):3721-33
references: 20639396
references: Hum Genet. 2009 Jun;125(5-6):527-39
references: 19252927
references: Cancer Res. 1999 Feb 1;59(3):602-6
references: 9973207
references: Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3328-35
references: 18421094
references: Am Heart J. 2011 Aug;162(2):246-53
references: 21835284
references: Cancer Causes Control. 2007 Feb;18(1):79-89
references: 17186424
references: Br J Nutr. 2010 May;103(9):1251-9
references: 20003627
references: Nutr J. 2007 Nov 13;6:41
references: 17997863
references: J Biol Chem. 2003 Mar 14;278(11):9035-41
references: 12381735
references: Biochem Biophys Res Commun. 2007 Dec 21;364(3):708-13
references: 17964545
references: J Nutr Biochem. 2011 Apr;22(4):344-50
references: 20471816
references: Free Radic Biol Med. 2007 Mar 1;42(5):608-16
references: 17291984
references: Eur J Cardiovasc Prev Rehabil. 2008 Feb;15(1):26-34
references: 18277182
references: Crit Rev Food Sci Nutr. 2012;52(9):815-29
references: 22698272
references: Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3691-6
references: 14993613
references: Pharmacogenet Genomics. 2005 May;15(5):311-9
references: 15864132
references: Am J Clin Nutr. 2012 May;95(5):1079-88
references: 22492364
references: Annu Rev Nutr. 2005;25:105-25
references: 16011461
references: Br J Nutr. 2006 Sep;96(3):516-22
references: 16925857
references: J Nutrigenet Nutrigenomics. 2009;2(6):292-301
references: 20588054
references: Carcinogenesis. 2009 Jun;30(6):977-81
references: 19346260
references: Mol Vis. 2011;17:2997-3004
references: 22171153
references: Free Radic Biol Med. 2009 Jan 1;46(1):70-7
references: 18952164
references: Free Radic Biol Med. 2009 Apr 15;46(8):1221-32
references: 19232538
references: Mutat Res. 2001 Oct 1;482(1-2):47-55
references: 11535248