IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Search for an association between polymorphisms of CX3CR1 gene and Hemolytic Uremic Syndrome progression in argentine patients with Shiga toxin-producing Escherichia coli (STEC) infections
Autor/es:
PANEK, CA; ABREY-RECALDE, MJ; RAMOS, MV; EXENI, A; GOGORZA, C; WAINSZTEIN, RE; EXENI, R; PALERMO MS
Lugar:
Amsterdam, The Netherlands
Reunión:
Congreso; 8th International Symposium on Shiga toxin (Verocytotoxin) producing Escherichia coli Infections (VTEC2012), , May 6-9, 2012; 2012
Institución organizadora:
VTEC-Holanda
Resumen:
Search for an association between polymorphisms of CX3CR1 gene  and Hemolytic Uremic Syndrome progression in argentine patients with Shiga toxin-producing Escherichia coli (STEC) infections.   1Panek, CA; 1Abrey-Recalde, MJ; 1Ramos, MV; 2Exeni, A; 3Gogorza, C.; 3Wainsztein, RE; 4Exeni, R; 1Palermo, MS.     Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Its typical form is a systemic complication of STEC infections that occurs in 10% of infected children. Two common single-nucleotide polymorphisms (SNPs) which cause amino acid changes in CX3CR1 protein (V249I and T280M) have been described. These two polymorphisms are in strong linkage disequilibrium, forming a common I249-M280 haplotype which was associated with a reduced risk of acute coronary events and atherosclerosis. The aim of our work was to assess the prevalence of CX3CR1 polymorphisms in our population and investigate the association with evolution to HUS in a case-control cohort in which we included STEC-infected children with HUS, without HUS (STECI) and age-matched healthy controls (HC).   DNA extraction from urine samples of 87 HUS, 14 STECI and 132 HC was performed using a DNA extraction kit. The SNPs of CX3CR1 gene were screened by PCR-RFLP technique. Allelic frequencies were calculated by gene counting. Hardy-Weinberg (H-W) equilibrium was tested by a X2 test with 1 degree of freedom. Unadjusted univariate analyses of the relationship of CX3CR1 genotypes with prevalent HUS progression was performed by cross-tabulation and results were expressed as odds ratios (ORs) with 95% confidence intervals (CI)s. Significance of the associations was evaluated based on X2 tests.   The genotype distribution for each allele considered separated was consistent with the H-W prediction among HC but not in HUS where excess of 249-II (p=0,004) was observed. Moreover, there was no significant difference in genotype frequencies between HUS and HC. The unadjusted ORs associated with I249 (VI+II vs. VV genotype) and M280 (TM+MM vs. TT genotype) were 0.82 (95% CI, 0.48-1.42, p=0,49) and 1.04 (95% CI, 0.57-1.89, p=1), respectively. The frequencies of combined genotypes and haplotypes were similar between HUS and HC. This cohort lacks power to analyze compound genotypes II-TT, II-MM, II-TM separately, but we could analyze VI-TT and VI-TM separately vs. VV-TT. There was no significant association between these combined genotypes and HUS progression. The OR after comparison of VI-TT vs. VV-TT was 0.46 (95% CI, 0,19-1,12, p=0,10) and VI-TM