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 (ICR) in the development of immune-mediated diseases. We investigated whether a g enetic polymorphism in the TCR constant alpha (C alpha) chain region might modify the susceptibility or progression of immunoglobulin A (IgA) nephropa thy. The TCR C alpha chain genotype was studied in 213 Japanese patients wi th IgA nephropathy and 73 individuals from the general population. A polyme rase chain reaction-based Taql restriction fragment length polymorphism ass ay (Taql RFLP) was applied on the 5' flanking region of the TCR C alpha fir st exon. The Taql-undigested (t) and Taql-digested (T) alleles showed simil ar genotype distributions between the patients with IgA nephropathy and con trols (tt:Tt:TT = 16.9%:46.5%:36.6% in IgA nephropathy v9.6%:58.9%:31.5% in controls; chi(2) = 1.9; P = not significant). To further investigate the r ole of TCR C alpha 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 gro ups were formed. The stable (S) group included 98 patients with renal funct ion that remained unchanged during an average follow-up of 10.7 +/- 0.4 (SE ) years. The progressive (P) group(n = 84) included patients with progressi vely declining renal function, with an average follow-up of 11.9 +/- 0.5 ye ars. The genotype distributions of the TCR C alpha chain gene polymorphisms between these two groups differed significantly (tt:Tt:TT = 25.5%:40.8%:33 .7% in S v10.7%:44.1%: 45.2% in P; chi(2) = 7.0; P < 0.05). The frequency o f the T allele was greater in the P group (67.3% in P v54.1% In S; chi(2) = 6.6; P = 0.01), The TT or Tt genotypes were more commonly observed in pati ents 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 p rognosis, conferring a potential risk for developing renal failure with tim e (odds ratio, 2.7; confidence interval, 1.2 to 6.0; P < 0.05), In summary, TCR C alpha chain genetic variability was associated with loss of renal fu nction over time in patients with IgA nephropathy, In conclusion, the TCR C alpha chain polymorphism might prove helpful to predict progression to chr onic renal failure in Japanese patients with IgA nephropathy. (C) 1999 by t he National Kidney Foundation, Inc.