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 kappaB-like gene (IKBL/NFKBIL1), homologous to the IkappaB family of proteins that regulate the NFkappaB family of transcription factors, is suggested as a putative inhibitor of NFkappaB. 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 (chi2=7.3; P=0.025 and chi2=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.
Ramasawmy
Rajendranath
R
Heart Institute (Incor), University of Sao Paulo School of Medicine, Sao Paulo, Brazil. ramasawm@usp.br
Faé
Kellen C
KC
Cunha-Neto
Edecio
E
Borba
Susan C P
SC
Ianni
Barbara
B
Mady
Charles
C
Goldberg
Anna C
AC
Kalil
Jorge
J
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002598:Chagas Cardiomyopathy / Q000235:genetics* / Q000469:parasitology; D002908:Chronic Disease; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014349:Trypanosoma cruzi / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000949:Histocompatibility Antigens Class II; C120111:NFKBIL1 protein, human