TMPRSS6, but not TF, TFR2 or BMP2 variants are associated with increased risk of iron-deficiency anemia.
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.
Key Laboratory of Nutrition and Metabolism, Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
Peng
P
An
Qian
Q
Wu
Hao
H
Wang
Yu
Y
Guan
Mingdao
M
Mu
Yijun
Y
Liao
Daizhan
D
Zhou
Pengkun
P
Song
Chunrong
C
Wang
Liping
L
Meng
Qingqing
Q
Man
Lixiang
L
Li
Jian
J
Zhang
Fudi
F
Wang
D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011990:Receptors, Transferrin / Q000235:genetics*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics*; D014168:Transferrin / Q000235:genetics*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D006454:Hemoglobins; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D014168:Transferrin; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human