Association of a T-cell receptor constant alpha chain gene polymorphism with progression of IgA nephropathy in Japanese patients.

Immunogenetic studies have suggested the role of the T-cell receptor (TCR) in the development of immune-mediated diseases. We investigated whether a genetic polymorphism in the TCR constant alpha (Calpha) chain region might modify the susceptibility or progression of immunoglobulin A (IgA) nephropathy. The TCR Calpha chain genotype was studied in 213 Japanese patients with IgA nephropathy and 73 individuals from the general population. A polymerase chain reaction-based TaqI restriction fragment length polymorphism assay (TaqI RFLP) was applied on the 5' flanking region of the TCR Calpha first exon. The TaqI-undigested (t) and TaqI-digested (T) alleles showed similar genotype distributions between the patients with IgA nephropathy and controls (tt:Tt:TT = 16.9%:46.5%:36.6% in IgA nephropathy v 9.6%:58.9%:31.5% in controls; chi(2) = 1.9; P = not significant). To further investigate the role of TCR Calpha chain gene polymorphism in renal prognosis, we analyzed those patients with IgA nephropathy in whom renal status had been monitored for a period of more than 3 years (n = 182). According to outcome, two groups were formed. The stable (S) group included 98 patients with renal function that remained unchanged during an average follow-up of 10.7 +/- 0.4 (SE) years. The progressive (P) group (n = 84) included patients with progressively declining renal function, with an average follow-up of 11.9 +/- 0.5 years. The genotype distributions of the TCR Calpha chain gene polymorphisms between these two groups differed significantly (tt:Tt:TT = 25.5%:40.8%:33.7% in S v 10.7%:44.1%:45.2% in P; chi(2) = 7.0; P < 0.05). The frequency of the T allele was greater in the P group (67.3% in P v 54.1% in S; chi(2) = 6.6; P = 0.01). The TT or Tt genotypes were more commonly observed in patients from the P group (89.3% of T allele carriers in P v 74.5% in S; chi(2) = 6.5; P = 0.01). It appeared the T allele might foreshadow a poor renal prognosis, conferring a potential risk for developing renal failure with time (odds ratio, 2.7; confidence interval, 1.2 to 6.0; P < 0.05). In summary, TCR Calpha chain genetic variability was associated with loss of renal function over time in patients with IgA nephropathy. In conclusion, the TCR Calpha chain polymorphism might prove helpful to predict progression to chronic renal failure in Japanese patients with IgA nephropathy.