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A variety of conditions lead to anemia, which affects one-quarter of the world's population. Previous genome-wide association studies revealed a number of genetic polymorphisms significantly associated with plasma iron status. To evaluate the association of genetic variants in genes involved in iron delivery and hepcidin regulation pathways with the risk of iron-deficiency anemia (IDA), the following single nucleotide polymorphisms were genotyped in 2139 unrelated elderly Chinese women: rs3811647 ( TF ), rs7385804 ( TFR2 ), rs235756 ( BMP2 ), and rs855791(V736A) and rs4820268 ( TMPRSS6,  encoding matriptase-2). We identified common variants in  TMPRSS6  as being genetic risk factors for both iron deficiency (OR rs855791 = 1.55,  P = 4.96 × 10 −8 ) and IDA (OR rs855791 = 1.78,  P = 8.43 × 10 −9 ).  TMPRSS6  polymorphisms were also associated with lower serum iron (SI) and hemoglobin levels, consistent with their associations to increased iron deficiency and anemia risk. Variants rs3811647 in  TF  and rs7385804 in  TFR2  were associated with reduced SI, serum transferrin and transferrin saturation levels; however, these variants were not associated with iron deficiency or anemia risk. Our findings suggest that  TF ,  TFR2  and  TMPRSS6  polymorphisms are significantly associated with decreased iron status, but only variants in  TMPRSS6  are genetic risk factors for iron deficiency and IDA.

TMPRSS6 , but not TF , TFR2 or BMP2 variants are associated with increased risk of iron-deficiency anemia