Cytogenetic location: 6p22.2 Genomic coordinates (GRCh38): 6:25,200,001-27,100,000
Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
---|---|---|---|---|
6p22.2 | [Transferrin serum level quantitative trait locus 2] | 614193 | 2 |
For a discussion of genetic heterogeneity of transferrin serum levels as a quantitative trait, see TFQTL1, 209300.
In a genomewide association study of Australians of European descent, Benyamin et al. (2009) found that the C282Y variant of the HFE gene (613609.0001, rs1800562) was associated with serum iron (p = 3.5 x 10(-11)), serum transferrin (p = 1.1 x 10(-10)), transferrin saturation (p = 4.3 x 10(-15)), and serum ferritin (see FTH1, 134770) (p = 4.5 x 10(-5)). C282Y explained 9.5%, 9.1%, 13.2%, and 3.7% of the variation in means of serum iron, serum transferrin, transferrin saturation, and serum ferritin levels, respectively. Three SNPs in the TF gene plus the HFE C282Y mutation explained about 40% of genetic variation in serum transferrin (p = 7.8 x 10(-25)).
In a population-based study of 1,832 Dutch individuals with a mean age of 62 years who were genotyped for SNPs within the HFE gene, Galesloot et al. (2013) found that a G-to-A SNP (rs1800562) had the most significant association with iron parameters, including iron levels, transferrin saturation, ferritin, and total iron-binding capacity (TIBC) (p between 1 x 10(-18) and 1 x 10(-3)). This association was independent of serum hepcidin (HAMP; 606464). However, the SNP was significantly associated with the ratio of hepcidin to ferritin and hepcidin to transferrin saturation. The findings did not support the hypothesis that variation in the HFE gene influences iron parameters by affecting hepcidin expression in response to systemic iron concentration.
Benyamin, B., McRae, A. F., Zhu, G., Gordon, S., Henders, A. K., Palotie, A., Peltonen, L., Martin, N. G., Montgomery, G. W., Whitfield, J. B., Visscher, P. M. Variants in TF and HFE explain about 40% of genetic variation in serum-transferrin levels. Am. J. Hum. Genet. 84: 60-65, 2009. [PubMed: 19084217] [Full Text: https://doi.org/10.1016/j.ajhg.2008.11.011]
Galesloot, T. E., Geurts-Moespot, A. J., den Heijer, M., Sweep, F. C. G. J., Fleming, R. E., Kiemeney, L. A. L. M., Vermeulen, S. H., Swinkels, D. W. Associations of common variants in HFE and TMPRSS6 with iron parameters are independent of serum hepcidin in a general population: a replication study. J. Med. Genet. 50: 593-598, 2013. [PubMed: 23794717] [Full Text: https://doi.org/10.1136/jmedgenet-2013-101673]