Common genetic variants in the interleukin-6 and chitotriosidase genes are associated with the risk for serious infection in children undergoing therapy for acute myeloid leukemia.
Infectious complications represent a substantial cause of morbidity and mortality in children undergoing therapy for acute myeloid leukemia (AML). Since it has been shown that alterations in innate immune pathways contribute to the risk for serious infections, we analyzed well-characterized variants in innate immune genes (TNF, IL6, IL8, MPO, CHIT, FCGR2A, TLR2, and TLR4) to determine their possible contribution to infectious complications during therapy for pediatric AML. The study population consisted of 168 North European Caucasian children enrolled on the clinical trial AML-BFM 93. We found an association between Gram-negative bacterial infection and common, functional variants in two genes, IL6 and CHIT. The risk for infection was significantly higher in children with the G allele in the IL6 promoter at -174 bp (P=0.026) and in patients with the H allele of CHIT (P=0.033). The promoter variant in IL6 has been shown to increase expression while the H allele disrupts both function and circulating levels. Our data suggest that variant alleles of both IL6 and CHIT could influence susceptibility to infection with Gram-negative bacteria in children undergoing therapy for AML. Follow-up studies, namely replication association studies and in vitro investigation of these common polymorphisms, are warranted to confirm these observations.
Lehrnbecher
T
T
Pediatric Hematology and Oncology, University of Frankfurt, Frankfurt, Germany. Thomas_lehrnbecher@yahoo.com
Bernig
T
T
Hanisch
M
M
Koehl
U
U
Behl
M
M
Reinhardt
D
D
Creutzig
U
U
Klingebiel
T
T
Chanock
S J
SJ
Schwabe
D
D
D000208:Acute Disease; D000293:Adolescent; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006090:Gram-Negative Bacteria / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000209:etiology*; D006596:Hexosaminidases / Q000097:blood / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000382:microbiology; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*
D015850:Interleukin-6; D006596:Hexosaminidases; C086400:chitotriosidase