Haptoglobin genotype modifies the association between dietary vitamin C and serum ascorbic acid deficiency

Abstract

Background: Haptoglobin (which is encoded by the Hp gene) is a hemoglobin-binding protein that has antioxidant properties and a common polymorphism that consists of 2 structurally different alleles: Hp1 and Hp2. The capacity of Hp2 to inhibit oxidation and vitamin C depletion is less than that of Hp1, but the influence on vitamin C requirements remains unknown. Objective: This study aimed to determine whether the Hp polymorphism modifies the association between dietary vitamin C and serum ascorbic acid deficiency (,11 lmol/L). Design: Nonsmoking men and women (n = 1046) between 20 and 29 y of age participated in the Toronto Nutrigenomics and Health Study. Blood samples were collected after the subjects had fasted overnight to determine serum ascorbic acid concentrations by HPLC and for genotyping. A 196-item food-frequency questionnaire was used to estimate vitamin C intake. Results: A gene-diet interaction on serum ascorbic acid was observed (P = 0.02). The overall odds ratio (95% CI) for serum ascorbic acid deficiency was 2.84 (1.73, 4.65) for subjects who did not meet the Recommended Dietary Allowance for vitamin C compared with those who did. The corresponding odds ratios were 4.77 (2.36, 9.65) for the Hp2-2 genotype and 1. 69 (0.80, 3.63) for carriers of the Hp1 allele. Conclusions: Individuals with the Hp2-2 genotype had an increased risk of deficiency if they did not meet the Recommended Dietary Allowance for vitamin C, whereas carriers of the Hp1 allele did not. The findings suggest that the greater antioxidant capacity of Hp1 might spare serum ascorbic acid.

Diet, Genetics, and Disease: A Focus on the Middle East and North Africa Region

“…Unlike Hp1 carriers, Hp2 homozygotes had lowest serum vitamin C concentrations when dietary vitamin C intake is insufficient. Thus, Hp1 has a greater antioxidant capacity preventing hemoglobin-ironrelated vitamin C oxidation and depletion [164].…”

Vitamin C deficiency: more than just a nutritional disorder

“…In this study, Cahill and El-Sohemy showed a gene-diet interaction on the serum ascorbic acid concentration. In contrast to carriers of the Hp 1 allele with a greater antioxidant capacity, Hp 2-2 subjects had an increased risk of deficiency if they did not meet the RDA for vitamin C (Cahill and El-Sohemy 2010). Hp acts to prevent the oxidative and toxic effects of the iron-containing heme in Hb (Na et al 2005).…”

“…Hp acts to prevent the oxidative and toxic effects of the iron-containing heme in Hb (Na et al 2005). The ascorbic acid stability in body fluids is lower in Hp 2-2 individuals (Cahill and El-Sohemy 2010;Delanghe et al 2007;Sadrzadeh and Eaton 1988;Langlois et al 1997). Hp 2-2 subjects are less efficient in removing free Hb from the plasma, which may favor an iron-mediated vitamin C depletion (Langlois et al 1997;Delanghe and Langlois 2002).…”

“…Research learns that the diet of the Inuit in the Hudson Bay (a region with a predominance of the Hp 1 allele) was mainly composed of animal sources, generally perceived as poor sources of vitamin C. It is assumed that the Inuit were able to obtain a minimum level of vitamin C (10 mg/day) from a diet of frozen/raw, fermented, and dried animal food, required to prevent scurvy (Fediuk 2000). As the stability of ascorbic acid is lower in Hp 2-2 individuals, the required daily intake of this nutrient is higher compared with the other Hp phenotypes (Cahill and El-Sohemy 2010;Delanghe et al 2007;Langlois et al 1997;Delanghe and Langlois 2002). Better tailored RDA guidelines for ascorbic acid taking into account the ethnical background could therefore contribute to a better nutritional health policy.…”

“…So, the clinical symptoms due to vitamin C deficiency develop very slowly. Beside the conflicting results of the therapeutic use of ascorbic acid in a wide range of diseases (Cahill and El-Sohemy 2010), vitamin C deficiency and scurvy have always been a major health problem. The in vivo instability of this antiscorbutic factor is due to its proneness to oxidation.…”