Variants in the promoter region of IKBL/NFKBIL1 gene may mark susceptibility to the development of chronic Chagas' cardiomyopathy among Trypanosoma cruzi-infected individuals

Chagas' disease, caused by Trypanosoma cruzi, is an inflammatory disorder leading to chronic Chagas cardiomyopathy (CCC). Only one third of T. cruzi-infected individuals progress to CCC while the others are considered asymptomatic (ASY). The human inhibitory κB-like gene (IKBL/NFKBIL1), homologous to the IκB family of proteins that regulate the NFκB family of transcription factors, is suggested as a putative inhibitor of NFκB. We investigated two functional polymorphisms, −62A/T and −262A/G, in the promoter of IKBL by PCR-RFLP analysis in 169 patients with CCC and 76 ASY. Genotype distributions for both −62A/T and −262A/G differed between the CCC and ASY (χ2 = 7.3; P = 0.025 and χ2 = 6.8; P = 0.03, respectively). Subjects, homozygous for the −62A allele, had three-fold risk of developing CCC compared with those carrying the TT genotype (P = 0.0095; Odds Ratio [OR] = 2.9; [95% CI 1.2-7.3]). Similar trend was observed for the −262A homozygotes (P = 0.005; OR = 2.7 [95% CI 1.3-6.0]. The haplotype −262A −62A was prevalent in patients with CCC (40% versus 24%; OR 2.1 [95% CI 1.4-3.3]; Pc = 0.0014). The IKBL locus itself or another critical gene in this region may confer susceptibility to the development of CCC.