Original Investigation

Human Genetics

, Volume 97, Issue 3, pp 369-374

First online:

Interleukin-1 receptor antagonist allele (ILIRN*2) associated with nephropathy in diabetes mellitus

  • Alexandra I. F. BlakemoreAffiliated withSection of Molecular Medicine, Department of Medicine, University of Sheffield, Royal Hallamshire Hospital
  • , Angela CoxAffiliated withSection of Molecular Medicine, Department of Medicine, University of Sheffield, Royal Hallamshire Hospital
  • , Ana-Maria GonzalezAffiliated withSection of Molecular Medicine, Department of Medicine, University of Sheffield, Royal Hallamshire Hospital
  • , Joanna K. MaskillAffiliated withSection of Molecular Medicine, Department of Medicine, University of Sheffield, Royal Hallamshire Hospital
  • , Marianne E. HughesAffiliated withDiabetes Centre, Royal Hallamshire Hospital
  • , R. Malcolm WilsonAffiliated withDiabetes Centre, Royal Hallamshire Hospital
  • , John D. WardAffiliated withDiabetes Centre, Royal Hallamshire Hospital
  • , Gordon W. DuffAffiliated withSection of Molecular Medicine, Department of Medicine, University of Sheffield, Royal Hallamshire Hospital

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Abstract

We have previously found association between an allele of the interleukin-1 (IL-1) receptor antagonist gene (ILIRN) and several inflammatory diseases, where IL-1 has been implicated in the inflammatory mechanism. We have now, therefore, tested the association of this specific allele (ILIRN*2) with complications of diabetes which have an inflammatory tissue component. We have tested the allele frequency of ILIRN*2 in 128 patients with insulin-dependent and 125 with non-insulin-dependent diabetes mellitus (NIDDM). There was a significant association between carriage of ILIRN*2 and diabetic nephropathy (P < 0.0001,P corrected < 0.0012). The association was significant in both types of diabetes, but the observed increase was highest in NIDDM, rising to double the control levels. It appears that ILIRN*2 is a novel genetic marker of severity of inflammatory complications of diseases rather than a marker of disease susceptibility. If the DNA polymorphism is associated with altered gene function, new therapeutic interventions may be possible.