Common variants in TMPRSS6 are associated with iron status and erythrocyte volume

Abstract

We report a genome-wide association study to iron status. We identify an association of SNPs in TPMRSS6 to serum iron (rs855791, combined P = 1.5×10−20), transferrin saturation (combined P = 2.2×10−23), and erythrocyte mean cell volume (MCV, combined P = 1.1×10−10). We also find suggestive evidence of association with blood haemoglobin levels (combined P = 5.3×10−7). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.

Increased susceptibility to iron deficiency of Tmprss6-haploinsufficient mice

“…In humans, genomewide association studies show that common TMPRSS6 variants influence iron parameters, Hb, and erythrocyte traits. [7][8][9][10] All these findings suggest that susceptibility to iron deficiency may be modulated by TMPRSS6 mutations even at the heterozygous state. …”

Genetic Loci Implicated in Erythroid Differentiation and Cell Cycle Regulation Are Associated With Red Blood Cell Traits

“…9,38 We identified 15 chromosomal loci associated with at least one RBC trait, including 11 loci associated with RBC traits in prior cohort studies. 4,5,7 Notably, genes present in 3 of the 4 loci newly identified in individuals of European ancestry (THRB, PTPLAD1, CDT1) and in 6 of the 11 replicated loci (KLF1, ALDH8A1, CCND3, SPTA1, FBXO7, TFR2/EPO) are implicated in erythroid differentiation and regulation of cell cycle in hematopoietic stem cells. Our report also highlights the potential use of the EMR in conducting GWAS of quantitative traits of medical importance.…”

“…2 The RBC traits have a substantial genetic component, with heritabilities of 0.56, 0.52, and 0.52 reported for RBC count, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH), respectively. 3 Recently, genomewide association studies (GWAS) in cohorts of European ancestry, [4][5][6][7] as well as in a Japanese cohort, 8 have reported multiple quantitative trait loci associated with one or more RBC traits.…”

Iron deficiency: new insights into diagnosis and treatment

“…Genome Wide Association Studies, including a recent meta-analysis, indicate that TMPRSS6 genetic variants associate with red cell and iron traits in Caucasian and Asian populations. [21][22][23] The most common associated TMPRSS6 variant (rs855791, A736V) influences serum hepcidin levels. 24 The genetic susceptibility to iron deficiency is of special interest for transfusion medicine because it has implications for blood donation.…”