Transferrin Polymorphism Influences Iron Status in Blacks

Abstract

Background: Genetic variants of human transferrin (TF) have been described, but little is known about their functional differences. We studied iron status according to TF phenotype in a healthy Zimbabwean population and in subjects at risk of African iron overload. Methods: The study population consisted of 483 nondrinkers, 31 drinking spouse pairs, and 5 family pedigrees (n = 88) with index cases of iron overload. TF phenotypes were determined using starch gel electrophoresis. To evaluate iron status, serum iron, total iron-binding capacity (TIBC), ferritin, and soluble TF receptors were measured, and the percentage of saturation and the serum iron:TF ratio were calculated. The binding of the TF variants was studied by equilibrium dialysis. Results: The reference population was characterized by a high TF D allele frequency (0.050) and a complete absence of homozygous TF DD individuals. Similar allele frequencies were observed in subjects at risk of African iron overload. In the reference population, male TF CD heterozygotes had significantly lower (P <0.01) values for serum iron, TIBC, TF saturation, and serum iron:TF ratio than the TF CC homozygotes; in females, only TIBC was significantly different. Overall red blood cell indices did not differ according to TF phenotype. In the population at risk of African iron overload, only serum iron:TF ratio was consistently significantly lower in TF CD phenotypes (P <0.05). After equilibrium dialysis, the amount of iron bound by TF was significantly lower (P <0.01) in TF CD individuals. Conclusions: The present data demonstrate a functional difference between TF phenotypes in blacks.

Association Between the Phenotypes of Haptoglobin and Tuberculosis in Ivory Coast-Haptoglobin Phenotypes and Tuberculosis

“…The p-value very close to the threshold of statistical significance deserves to be confirmed on a larger sample population or on a population of heterogeneous tuberculosis from several sites in order to favor a random distribution of the Hp alleles. This result disagrees with those of the Kasvosve et al (2000) study on tuberculosis patients High positive (1 to 3 cross) microscopies were found in groups of Hp1-1 and 2-1 phenotypes but this was not statistically significant.…”

“…These two results indicated the same trend which was similar to those of Kaminskaia, Abdullaev, Elufimova, Mitinskaia, and Iukhimenko (2004) and Philemond et al (2017). However, they differed from what reported by many previous studies in which the Hp2-2 phenotype is less protective and therefore more expected to be found in patients than in controls (Langlois & Delanghe , 1996, McDermid & Prentice , 2006Kasvosve et al, 2000).…”

“…Therefore, the susceptibility of patients to certain pathologies including tuberculosis (TB) could be associated to the phenotype of their Hp. Studies have shown that tuberculosis subjects with Hp2-2 phenotype have an increased risk of mortality and increased susceptibility to developing severe renal tuberculosis compared to other phenotypes (Fedoseava, Lusopova, Chukanova & Pospelov, 1993;Kasvosve et al, 2000). The prevalence of tuberculosis in Côte d'Ivoire is around 661 cases / 100 000 inhabitants (Programme national de lutte contre la tuberculose [PNLT], 2012) and also has specific features (PNLT, 2012).…”

Iron overload and prolonged ingestion of iron supplements: Clinical features and mutation analysis of hemochromatosis‐associated genes in four cases

“…Common polymorphisms in the haptoglobin gene (HP) or in mitochondrial DNA have been associated with more severe iron overload phenotypes in some studies [31,32] but not in other reports [19,33,34]. Transferrin mutations influence serum iron measures in sub-Saharan blacks, but do not appear to be associated with most cases of iron overload [19,35,36]. A mutation in the ironresponsive element of the ferritin heavy-chain gene (FTH1) accounted for iron overload in some members of a Japanese family [37].…”

Monitoring of transferrin isoforms in biological samples by capillary electrophoresis

“…No samples were found that encompassed Tf-BB or Tf-DD variants. Identification of genetic variants by CZE is straightforward provided that the resolution of the Tf isoforms is sufficient [29,30,42,80,81,83,118,126,142,144,145]. It is easiest done with spiking the unknown sample with a serum of a known variant and reanalysis of the mixture [142].…”