Gan, W.Guan, Y.Wu, Q.An, P.Zhu, J.Lu, L.Jing, L.Yu, Y.Ruan, S.Xie, D.Makrides, M.Gibson, R.Anderson, G.Li, H.Lin, X.Wang, F.2012-11-132012-11-132012American Journal of Clinical Nutrition, 2012; 95(3):626-6320002-91651938-3207http://hdl.handle.net/2440/74201BACKGROUND: 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.en© 2012 American Society for NutritionHumansDiabetes Mellitus, Type 2IronSerine EndopeptidasesAntimicrobial Cationic PeptidesHemoglobinsMembrane ProteinsLinear ModelsRisk FactorsCohort StudiesHomeostasisGenotypePolymorphism, Single NucleotideAllelesMiddle AgedChinaFemaleMaleFerritinsGenome-Wide Association StudyMendelian Randomization AnalysisHepcidinsAsian PeopleJournal article002011681510.3945/ajcn.111.0256840003006387000142-s2.0-8486322972825763Makrides, M. [0000-0003-3832-541X]Gibson, R. [0000-0002-8750-525X]