Genetics, transferrin variants

HPLC traces of sera for some of the most common genetic transferrin variants, the transferrin BC and CD heterozygotes, and a transferrin C heterozygote tentatively identified as C2C3 5 are shown in Figure 6.3d-f. In addition to these, a number of very rare variants, including the transferrin B homozygote, have been identified (unpublished work). 

The CDG-I pattern resembles that observed after chronic alcohol consumption, albeit the relative increases were much higher in CDG-Ia (Figure 6.4). However, because CDG testing is typically performed at young age, there is usually no risk of false-positive results due to alcohol misuse. Furthermore, the CDG patterns are clearly distinguishable from those observed with the most common genetic transferrin variants, which may cause falsely high or low values with the minicolumn immunoassays for CDT. 

Wetlaufer, D. B. Genetic variants of bovine serum transferrin. Compt. Rend. Trav. Lab. Carlsberg 32, 125 (1961). 

O Keefe, D. O., and Draper, R. K. (1988). Two pathways of transferrin recycling evident in a variant of mouse LMTK-cells. Somatic Cell. Mol. Genet. 14, 473-487. 

Transferrin is commonly assayed by immunochemical methods, including immunoturbidimetry and immuno-nephelometry. It migrates in the Pi region on routine serum electrophoresis as noted previously, genetic variants may cause problems in interpretation of these patterns. 

Multiple bands, absent bands, or different mobility of normal bands. These may be due to genetic variants or deficiency, such as AAT in the ai-region and transferrin or C3 in the p-region. 

Over 95% of plasma iron is in the Fe + state bound to the glycoprotein transferrin, a monomeric /I i-globulin (M.W. 80,000). Electrophoretic studies have revealed the existence of 21 genetic variants. In some, single-amino-acid substitutions account for variation in electrophoretic mobility. Transferrin is synthesized primarily in the liver and appears at the end of the first month of fetal development. Its half-life in humans is about 8 days. Desialylation may be a requirement for its removal from plasma by the liver, as it is for other plasma proteins (Chapter 10). In fact, asialotransferrin is more rapidly cleared from plasma than transferrin. It is not required for intestinal absorption of iron. 

Human transferrin displays genetic polymorphism with transferrin C being the most common phenotype in all populations, whereas allelic B (lower isoelectric point, p7) and D (higher p7) variants, with a different primary structure but a normal set of glycans, occur at lower frequencies. ... 

Modifications of the expression of plasma proteins can be related to genetic variations, complex combinations of post-translational modifications, alterations directly or indirectly related to diseases, or combinations of these mechanisms. Genetic variants of proteins such as haptoglobin, Gc-globulin, apolipoprotein E, apolipoprotein A-1, transferrin, or alpha-1-antitrypsin can be identified using 2-DE (Anderson and Anderson, 1979 Rosenblum et al, 1983 Tissot et al, 1993b Tissot et al, 2000b). 

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