Association of a uteroglobin polymorphism with rate of progression in patients with IgA nephropathy.
Uteroglobin gene-disrupted mice develop a nephritis very similar to immunoglobulin A (IgA) nephropathy. Megsin codes for a protein overexpressed in mesangium in patients with IgA nephropathy. Both are candidate genes that might have variants associated with an accelerated progression in patients with IgA nephropathy. We performed an association study of patients with IgA nephropathy and matching control subjects to test whether the G38A polymorphism in the uteroglobin gene, the C2093T polymorphism in the megsin gene, or the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism is associated with IgA nephropathy or rate of disease progression in patients with IgA nephropathy. Of 110 patients with IgA nephropathy, 87 patients were followed up for at least 3 years for the progression study. We also studied 104 healthy volunteers. The uteroglobin, megsin, and ACE polymorphisms were not distributed differently in the 110 patients with IgA nephropathy compared with healthy controls; Hardy-Weinberg equilibrium criteria were fulfilled. The GG genotype of the G38A uteroglobin polymorphism was more common in patients with progression (odds ratio [OR], 3.5; P< 0.006) than the AG+AA genotypes. The G allele was also more common (OR, 2.6; P< 0.009) in patients with versus without progression. The 1/serum creatinine over time plot (in deciliters per milligram per day) was sevenfold steeper in GG patients than the other two genotypes (P = 0.08). No significant associations with disease progression were found for the other gene polymorphisms, and a multivariate analysis showed no interactions. We suggest the hypothesis that the uteroglobin gene contains variant(s) with a bearing on progression rate in patients with IgA nephropathy.
Szelestei
T
T
Department of Internal Medicine-Nephrology, University of Pécs, Hungary.
Bähring
S
S
Kovács
T
T
Vas
T
T
Salamon
C
C
Busjahn
A
A
Luft
F C
FC
Nagy
J
J
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D015843:Serpins / Q000235:genetics*; D014598:Uteroglobin / Q000235:genetics*
C114170:SERPINB7 protein, human; D015843:Serpins; D014598:Uteroglobin; D007703:Peptidyl-Dipeptidase A