G protein beta3 subunit C825T polymorphism in primary IgA nephropathy.
BACKGROUND
The T allele of the G protein beta3 subunit (GNB3) C825T polymorphism has been associated with increased signal transduction, increased activity of the kidney Na+/H+ exchanger, and also with late-onset essential hypertension. Hypertension is a strong independent risk factor for progression in IgA nephropathy (IgAN).


METHODS
We have studied this polymorphism in a regularly followed cohort of 299 biopsy-proven incident cases of IgAN, collected from 1989 to 1999 [208 males (70%)] and compared the genotypes and alleles distributions to 303 local Caucasian controls matched for the male predominance (214 males). The technique used was a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with BseDI as restriction enzyme and specific primers, followed by gel electrophoresis.


RESULTS
The TT, CT, and CC genotype frequencies were 13.7%, 45.8%, and 40.5% in IgAN, respectively, versus 7.6%, 47.2%, and 45.2% in controls, respectively (chi(2)= 6.16; P= 0.05). The excess of TT patients versus non-TT was significant in IgAN versus controls (chi(2)= 5.94; P= 0.015). The T allele frequency was 0.366 in IgAN versus 0.312 in controls (chi(2)= 3.97; P= 0.05). This data indicated that this polymorphism had a significant but mild influence on the occurrence/initiation of IgAN (RR = 1.81; 95% CI 1.07-3.07). In contrast, we could not demonstrate any significant and sustained difference in the clinical presentation and evolution of the homozygous TT patients compared to non-TT patients (CC + CT) despite a mean and median follow-up about 10 years. The progression to arterial hypertension or to chronic renal failure or to end-stage renal failure (ESRF) was not significantly different. In addition, multivariate Cox regression analysis excluded a significant independent role of C825T polymorphism on progression.


CONCLUSIONS
The C825T GNB3 polymorphism had a mild influence on occurrence/initiation of IgAN, but played no significant role in the progression of the disease.
Thibaudin
Lise
L
Department of Nephrology, Dialysis and Renal Transplantation, University North Hospital, Saint Etienne, France.
Berthoux
Patricia
P
Thibaudin
Damien
D
Mariat
Christophe
C
Berthoux
François
F
D000328:Adult; D000483:Alleles; D003596:Cytosine; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000503:physiopathology; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D016019:Survival Analysis; D013941:Thymine
C454420:G-protein beta3 subunit; D003596:Cytosine; D020962:Heterotrimeric GTP-Binding Proteins; D013941:Thymine