Gene-environment Interactions of Specific TF and HAMP Gene Variants in Relation to Iron Status in Black South Africans

Abstract

Objectives: Besides understanding the genetic determinants of iron status, investigations on how these interact with environmental factors to influence iron status are crucial. The objective of our study was to determine interaction between single nucleotide polymorphisms (SNPs) within the transferrin gene (TF-rs1799852) and hepcidin antimicrobial peptide gene (HAMP-rs10421768) and environmental factors within a population of black South Africans. Methods: Genotypes were determined in a subset of women of Tswana ancestry (n=686) who were part of the South African prospective urban and rural epidemiological (PURE) study, and were associated with concentrations of serum ferritin (SF), soluble transferrin receptor (STfR) and body iron (BI). C-reactive protein was included as a co-variate. Results: Iron intake was 11.0 g/d and 13.5 g/d in the rural and urban site respectively. Overall, rural subjects had lower SF and BI, and higher sTfR in comparison to their urban counterparts (P<0.05). Concentrations of SF, sTfR and BI were not different between rs10421768 genotypes. Concentrations of SF and BI in rural subjects harbouring the mutant allele (A) at rs1799852 were, 28.2µg/L and 26.3mg/kg. compared to 87.3µg/L, and 31.1mg/kg in homozygous wild type subjects (P<0.05). Urban subjects presented with no such differences. Conclusions: Residential area influenced the association of rs1799852 with serum concentration of ferritin, transferrin receptor and body iron, highlighting the importance to investigate gene-environment interactions.