Association of TMPRSS6 polymorphisms with ferritin, hemoglobin, and type 2 diabetes risk in a Chinese Han population

Wei Gan, Yu Guan, Qian Wu, Peng An, Jingwen Zhu, Ling Lu, Li Jing, Yu Yu, Sheng Ruan, Dong Xie, Maria Makrides, Robert A. Gibson, Gregory J. Anderson, Huaixing Li, Xu Lin, Fudi Wang

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48 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)626-632
Number of pages7
JournalAmerican Journal of Clinical Nutrition
Issue number3
Publication statusPublished or Issued - 1 Mar 2012

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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