Functional polymorphism in Z-DNA-forming motif of promoter of SLC11A1 gene and type 1 diabetes in Japanese subjects: association study and meta-analysis

Metabolism. 2005 May;54(5):628-33. doi: 10.1016/j.metabol.2004.12.006.


The association of the polymorphism of the Z-DNA-forming repeats in the promoter region of SLC11A1 (solute carrier family 11 member 1), formerly designated NRAMP1 (natural resistance associated macrophage protein 1), with type 1 diabetes was studied in a total of 244 Japanese subjects. Three alleles were detected in Japanese subjects. In diabetic patients, allele 2 was less frequent and allele 3 was more frequent, albeit not significantly, than in control subjects. Allele 2 was significantly ( P < .024) less frequent whereas allele 3 was more, albeit not significantly, frequent in the younger onset group than in the control subjects. In patients with a susceptible HLA allele, DRB1*0405 or DRB1*0901 , the frequency of allele 2 was significantly ( P < .013) lower and that of allele 3 tended to be higher than that in patients without either DRB1*0405 or DRB1*0901 . The protective effect of allele 2 against type 1 diabetes and other autoimmune diseases was confirmed by meta-analysis (summary odds ratio, 0.71, 95% confidence interval, 0.53-0.96). Because allele 2 was shown to be associated with low expression of SLC11A1 and protection against another autoimmune disease, rheumatoid arthritis, the negative association of allele 2 with autoimmune type 1 diabetes in the present study suggests that a less active immune system in subjects with allele 2 may protect individuals from autoimmune diseases.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Motifs
  • Asian People / genetics*
  • Cation Transport Proteins / genetics*
  • DNA, Z-Form / biosynthesis*
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Gene Frequency
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics


  • Cation Transport Proteins
  • DNA, Z-Form
  • natural resistance-associated macrophage protein 1