临床时讯 ＞ 临床研究
Hum Mol Genet. 2012 Feb 8. [Epub ahead of print]
TMPRSS6, but not TF, TFR2, or BMP2 Variants are Associated with Increased Risk of Iron Deficiency Anemia.
An P, Wu Q, Wang H, Guan Y, Mu M, Liao Y, Zhou D, Song P, Wang C, Meng L, Man Q, Li L, Zhang J, Wang F.
Group of Bio-Metal Metabolism, 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, China, 200031.
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, the following single nucleotide polymorphisms (SNPs) 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 iron-deficiency anemia (OR(rs855791) = 1.78, P = 8.43×10(-9)). TMPRSS6 polymorphisms were also associated with lower serum iron 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 serum iron, 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 iron-deficiency anemia.
Am J Clin Nutr. 2012 Feb 1. [Epub ahead of print]
Association of TMPRSS6 polymorphisms with ferritin, hemoglobin, and type 2 diabetes risk in a Chinese Han population.
Gan W, Guan Y, Wu Q, An P, Zhu J, Lu L, Jing L, Yu Y, Ruan S, Xie D, Makrides M, Gibson RA, Anderson GJ, Li H, Lin X, Wang F.
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
BACKGROUND: Transmembrane protease serine 6 (TMPRSS6) regulates iron homeostasis by inhibiting the expression of hepcidin. Multiple common variants in TMPRSS6 were significantly associated with serum iron in recent genome-wide association studies, but their effects in the Chinese remain to be elucidated.
OBJECTIVE: The objective was to determine whether the TMPRSS6 single nucleotide polymorphisms (SNPs) rs855791(V736A) and rs4820268(D521D) were associated with blood hemoglobin and plasma ferritin concentrations and risk of type 2 diabetes in Chinese individuals.
DESIGN: The SNPs rs855791(V736A) and rs4820268(D521D) in the TMPRSS6 gene were genotyped and tested for their associations with plasma iron and type 2 diabetes risk in 1574 unrelated Chinese Hans from Beijing.
RESULTS: The 2 TMPRSS6 SNPs rs855791(V736A) and rs4820268(D521D) were both significantly associated with plasma ferritin (P ≤ 0.0058), hemoglobin (P ≤ 0.0013), iron overload risk (P ≤ 0.0068), and type 2 diabetes risk (P ≤ 0.0314). None of the associations with hemoglobin or plasma ferritin remained significant (P ≥ 0.1229) when the 2 variants were both included in one linear regression model. A haplotype carrying both iron-lowering alleles from the 2 TMPRSS SNPs showed significant associations with lower hemoglobin (P = 0.0014), lower plasma ferritin (P = 0.0027), and a reduced risk of iron overload (P = 0.0017) and of type 2 diabetes (P = 0.0277).
CONCLUSIONS: These findings suggest that TMPRSS6 variants were significantly associated with plasma ferritin, hemoglobin, risk of iron overload, and type 2 diabetes in Chinese Hans. The type 2 diabetes risk conferred by the TMPRSS6 SNPs is possibly mediated by plasma ferritin.