Common TMPRSS6 mutations and iron, erythrocyte, and pica phenotypes in 48 women with iron deficiency or depletion

Abstract

Background TMPRSS6 A736V is associated with lower transferrin saturation (TS), hemoglobin (Hb), and mean corpuscular volume (MCV) levels in general adult populations. We sought to identify relationships of TMPRSS6 K253E, A736V, and Y739Y to iron, erythrocyte, and pica phenotypes in women with iron deficiency or depletion. Methods We tabulated observations on 48 outpatient non-pregnant women who had iron deficiency (serum ferritin (SF) <14 pmol/L and TS <10%) or iron depletion (SF<112 pmol/L). We performed direct sequencing of TMPRSS6 exons 7 and 17 in each patient. We used age, TS, SF, Hb, MCV, pica, and TMPRSS6 allele positivity (dichotomous) or mutation genotypes (trichotomous) as variables for analyses. Results Forty-six women were white; two were black. 58.3% had iron deficiency. 45.8% had pica (pagophagia, each case). Allele frequencies were 41.7% (K253E), 36.5% (A736V), and 39.6% (Y739Y). K253E frequency was greater in women with TS ≥10% (p = 0.0001). Y739Y was more frequent in women with TS <10% (p = 0.0135). Mean TS was also lower in women positive for Y739Y (6 ± 4% vs. 13 ± 16%, respectively; p = 0.0021). In multiple regressions, neither K253E, A736V, nor Y739Y genotypes were significantly associated with other variables. Conclusions TMPRSS6 K253E frequency was greater in women with TS ≥10%. Frequency of Y739 was greater in women with TS <10%. Mean TS was lower in women with Y739Y. We observed no other significant relationship of TMPRSS6 K253E, A736V, or Y739Y with iron, erythrocyte, or pica phenotypes.

Physiology of Iron Metabolism

“…The first protein is hemojuvelin (HJV) a glycosylphosphatidylinositol-linked membrane protein [41], the second is Mt2 [42], which regulates the levels of membrane-bound HJV, and the third is neogenin, a ubiquitously expressed transmembrane protein with multiple functions [43,44,45,46,47,48]. The gene of Mt2 carries several polymorphisms that have been linked to iron metabolic parameters, notably in patients presenting with iron-refractory iron-deficient anemia [49,50,51,52,53,54,55,56,57,58]. …”

Qualitative assessment of pica experienced by frequent blood donors

“…Sample questions are provided in Table . This would allow for larger studies in blood donors, as well as other populations, that could be designed to define the genetics and biochemistry in relation to the iron deficiency associated with pica, which are essentially unknown at this time …”

Pica for Uncooked Basmati Rice in Two Women with Iron Deficiency and a Review of Ryzophagia

“…Other factors driving pica in adults with iron deficiency are related to geographic location, race/ethnicity, cultural attributes, available pica items, age, and gender [ 6 , 37 ]. Gross epithelial manifestations of iron deficiency or depletion such as glossitis or cheilosis or common alleles of the TMPRSS6 gene that encodes matriptase-2, a serine protease that represses hepcidin, probably do not cause or influence pica [ 6 , 38 ].…”