Vitamin C deficiency and scurvy are not only a dietary problem but are codetermined by the haptoglobin polymorphism.
Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp) shows a genetic polymorphism with 3 major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) that show important functional differences. Despite an adequate nutritional supply, in Hp 2-2 individuals (most common among Asian populations) vitamin C is markedly lower in concentration and particularly prone to oxidation in vivo. Therefore, susceptibility to subclinical and clinical vitamin C deficiency (scurvy) is partly genetically determined. The genetic advantage of the Hp1 allele as a vitamin C stabilizing factor helps to elucidate the direction and successes of long-distance sea crossing human migrations in history. Clinical trials demonstrated Hp phenotype-related effects of antioxidant treatment. Because vitamin C is a first line antioxidant, Hp polymorphism and its effects on vitamin C have major clinical consequences; a marked difference in genetic susceptibility toward atherosclerosis between Hp phenotypes is attributable to variation in LDL oxidation. The classical view of vitamin C and scurvy being a pure nutritional condition needs to be updated. These findings should foster research investigating the role of Hp polymorphism in human disease, and in vitamin C deficiency and atherosclerosis in particular.
Delanghe
Joris R
JR
Department of Clinical Chemistry, University Hospital Ghent, Ghent, Belgium. joris.delanghe@ugent.be
Langlois
Michel R
MR
De Buyzere
Marc L
ML
Torck
Mathieu A
MA
D044467:American Indian or Alaska Native; D001205:Ascorbic Acid / Q000008:administration & dosage*; D001206:Ascorbic Acid Deficiency / Q000235:genetics*; D044466:Asian People; D004032:Diet; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006242:Haptoglobins / Q000235:genetics*; D049669:History, 16th Century; D049670:History, 17th Century; D049672:History, 19th Century; D049691:History, Medieval; D006801:Humans; D011110:Polymorphism, Genetic; D012614:Scurvy / Q000453:epidemiology / Q000235:genetics* / Q000266:history; D044465:White People
D006242:Haptoglobins; D001205:Ascorbic Acid