title: Genetic determinants for body iron store and type 2 diabetes risk in US men and women.
abstract: BACKGROUND
  High body iron store has been associated with an increased risk of type 2 diabetes (T2D); it remains unknown whether the genetic variants related to body iron status affect T2D risk. We aimed at comprehensively investigating the associations between the genetic variants related to body iron status and the T2D risk.
  
  
  RESULTS
  Six common SNPs related to body iron status from recent genome-wide association (GWA) studies were determined in the Nurses' Health Study (NHS; 1,467 diabetic cases and 1,754 controls) and the Health Professionals Follow-up Study (HPFS; 1,124, diabetic cases and 1,298 controls). Plasma levels of ferritin, soluble transferrin receptor (sTfR), and transferrin were measured in NHS. Significant associations were observed for loci in TPMRSS6 with sTfR (P = 3.47×10(-6)), TF with transferrin (P = 0.0002 to 1.72×10(-10)); and HFE with ferritin (P = 0.017 to 1.6×10(-8)), sTfR (P = 0.007 to 7.9×10(-6)), and transferrin (P = 0.006 to 0.0007). The six SNPs together explained 5.7%, 2.7%, and 13.3% of the variation in plasma levels of ferritin, sTfR, and transferrin. After adjustment for the conventional risk factors, the T allele of SNP rs855791 in the TPMRSS6 gene was significantly associated with a 19% decreased risk of T2D (OR = 0.81; 95% CI = 0.66-0.98; P = 0.03) in men. Multiple tests attenuated this significant association to null. No associations were observed in women. SNPs at HFE and TF were not associated with diabetes risk in either sex. Dietary iron intake did not modify the associations of the newly identified loci with diabetes risk.
  
  
  CONCLUSIONS
  The newly identified iron-related SNP rs855791 in TPMRSS6 was nominally associated with a decreased risk of T2D in men but not in women. The apparent differences by gender warrant further study.
authors: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors: Meian
authors: M
authors: He
authors: Tsegaselassie
authors: T
authors: Workalemahu
authors: JoAnn E
authors: JE
authors: Manson
authors: Frank B
authors: FB
authors: Hu
authors: Lu
authors: L
authors: Qi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006282:Health Personnel; D006418:Heme / Q000378:metabolism; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D014168:Transferrin / Q000235:genetics; D014481:United States
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D006418:Heme; D007501:Iron