Uteroglobin gene polymorphisms affect the progression of immunoglobulin A nephropathy by modulating the level of uteroglobin expression

Pharmacogenetics. 2001 Jun;11(4):299-305. doi: 10.1097/00008571-200106000-00004.


Uteroglobin (UG) is an anti-inflammatory/immunomodulatory protein. Targeted disruption of UG rendered mouse glomerulonephritis resembling immunoglobulin (Ig)A nephropathy (IgAN). Sequence analysis on exon 1 of UG showed several putative binding sites for transcription factors, and polymorphisms in this site might influence the expression level of UG as a competitive protein. We speculated that the single nucleotide polymorphism at the 38th nucleotide (A to G) from the transcription initiation site of UG exon 1 would impact the progression of IgA nephropathy (IgAN). Polymerase chain reaction-restriction fragment length polymorphism and single-strand conformation polymorphism were instituted to determine the genetic polymorphism. Luciferase assay was performed using the gene constructs containing a region 404-bp long located upstream of UG exon 1 initiation site to analyse whether this polymorphism would affect the expression level. UG polymorphism was distributed no differently in patients with IgAN (n = 111) compared to 60 healthy control subjects. An excess of A genotype was found in one patient having progressive disease (P = 0.03) and the risk for the disease progression increased as the number of A alleles increased (P for trend = 0.03) after follow-up for 116 months. The odds ratio for progression with the AA genotype was 4.9 (95% Cl = 1.0-23.9) compared to patients having the GG genotype. Significant interactive effects of hypertension and genetic polymorphisms of UG on the disease progression were observed (P for interaction = 0.001). In the luciferase assay, the gene construct with A at the 38th site showed a decreased activity of 74 +/- 8.4% compared to that showed by G gene construct. Our results suggest that polymorphism at the 5' UTR region of UG exon 1 is an important marker for the progression of IgAN and may modulate the level of protein expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Adult
  • Animals
  • Base Sequence
  • Case-Control Studies
  • DNA / genetics
  • Exons
  • Gene Expression
  • Gene Frequency
  • Genetic Markers
  • Genotype
  • Glomerulonephritis, IGA / complications
  • Glomerulonephritis, IGA / genetics*
  • Humans
  • Kidney Failure, Chronic / etiology
  • Mice
  • Middle Aged
  • Molecular Sequence Data
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Polymorphism, Single-Stranded Conformational
  • Prognosis
  • Risk Factors
  • Uteroglobin / genetics*


  • 5' Untranslated Regions
  • Genetic Markers
  • DNA
  • Uteroglobin