G protein β3 subunit C825T polymorphism in primary IgA nephropathy

Thibaudin, Lise; Berthoux, Patricia; Thibaudin, Damien; Mariat, Christophe; Berthoux, François
July 2004
Kidney International;Jul2004, Vol. 66 Issue 1, p322
Academic Journal
G protein β3 subunit C825T polymorphism in primary IgA nephropathy. Background. The T allele of the G protein β3 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 (χ2= 6.16; P= 0.05). The excess of TT patients versus non-TT was significant in IgAN versus controls (χ2= 5.94; P= 0.015). The T allele frequency was 0.366 in IgAN versus 0.312 in controls (χ2= 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. Conclusion. The C825T GNB3 polymorphism had a mild influence on occurrence/initiation of IgAN, but played no significant role in the progression of the disease.


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