Korean J Nephrol.  2001 Jan;20(1):59-66.

The Effect of Uteroglobin Exon 1, 5' Untranslated Region Polymorphism on the Progression of IgA Nephropathy

• Oh YK
• Kwon DY
• Zheng SH
• Oh KH
• Kim HL
• Kim KS
• Kim YS
• Ahn C
• Han JS
• Kim S
• Lee JS

Abstract

Uteroglobin(UG) is an anti-inflammatory/immunomodulatory protein secreted by the epithelial cells of vertebrates. Targeted disruption of UG rendered mouse glomerulonephritis resembling IgA nephropathy(IgAN). Sequence analysis on exon 1 of UG showed several putative binding sites for transcription factors, and genetic 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 from the transcription initiation site of UG exon 1 would impact the progression of IgAN. PCR-RFLP was instituted to determine the genetic polymorphism in 60 patients with IgAN. Other measures like SSCP and direct sequencing were also adopted for the verification of polymorphic sites. Seventeen patients with IgAN(28%) were homozygous for adenine at position 38(38AA), 26 patients(43%) were heterozygous(38AG), and 17 patients(28%) were homozygous for the polymorphism(38GG), which was similar to the pattern obtained from the 60 normal controls. The amount of daily proteinuria, presence of hypertension, the level of IgA, and the amount of IgA-fibronectin(FN) complexes was similar between the genotypes. Serum IgA-FN level did not influence the progression of disease. However, 8 out of 17 patients (47%) with the AA genotype had progressive disease(PD), 10 of 26 patients(38%) with the AG genotype had PD, and only 1 of 17 patients(6%) with GG homozygocity had PD after 94+/-30.1 months of follow-up(mean+/-S.D.). The odds ratio for the progression of renal disease in patients with the AA genotype was 14.93(p=0.0355) and in patients with AG genotype was 12.94(p=0.0496) compared with patients have the GG genotype. Moreover, serum creatinine at the time of kidney biopsy was higher in patients with AA and AG genotypes than in patients with the GG genotype(1.5+/-0.69 : 1.3+/-0.53 : 1.0+/-0.31mg/dL; AA : AG : GG; p=0.0137 AA vs. GG; p=0.0269 AG vs. GG). Our results suggest that polymorphism at the 5' UTR region of UG exon 1 is an important marker for the progression of IgAN.

Keyword

Uteroglobin; IgA nephropathy

MeSH Terms

5' Untranslated Regions*
Adenine
Animals
Binding Sites
Biopsy
Creatinine
Epithelial Cells
Exons*
Genotype
Glomerulonephritis
Glomerulonephritis, IGA*
Humans
Hypertension
Immunoglobulin A*
Kidney
Mice
Odds Ratio
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Polymorphism, Single-Stranded Conformational
Proteinuria
Sequence Analysis
Transcription Factors
Transcription Initiation Site
Uteroglobin*
Vertebrates
5' Untranslated Regions
Adenine
Creatinine
Immunoglobulin A
Transcription Factors
Uteroglobin