title: 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) <14pmol/L and TS <10%) or iron depletion (SF<112pmol/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.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA, USA. plee@scripps.edu
authors.forename: Pauline L
authors.initials: PL
authors.lastname: Lee
authors.forename: J Clayborn
authors.initials: JC
authors.lastname: Barton
authors.forename: Peter L
authors.initials: PL
authors.lastname: Khaw
authors.forename: Sarah Y
authors.initials: SY
authors.lastname: Bhattacharjee
authors.forename: James C
authors.initials: JC
authors.lastname: Barton
mesh_terms: D000328:Adult; D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000097:blood* / Q000235:genetics*; D004909:Erythrocyte Indices; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007501:Iron / Q000097:blood*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010842:Pica / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D007501:Iron; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human