Susceptibility to acute myeloid leukemia: Influence of genetic variants of interleukins 37 and 38

Interleukin (IL)-37 and IL-38 are anti-inflammatory cytokines encoded by IL37 and IL1F10 genes, respectively. Recently, it has been proposed that missense single nucleotide polymorphisms (SNPs) of IL37 (rs3811046 G/T and rs3811047 A/G) and 5′-untranslated region SNPs of IL1F10 (rs3811050 C/T and rs3811051 T/G) may influence susceptibility to some inflammatory disorders. Inflammation has also been shown to play a key role in pathogenesis of acute myeloid leukemia (AML). Therefore, it is reasonable to hypothesize that rs3811046, rs3811047, rs3811050, and rs3811051 may have a role in susceptibility to AML. A case-control study was conducted on 131 AML patients and 169 controls to investigate the association of these SNPs with AML risk. SNP genotypes were determined using TaqMan allelic discrimination, a real-time PCR-based method. Results revealed that mutant alleles (T, G, and T) and corresponding homozygous genotypes (TT, GG, and TT) of rs3811046, rs3811047, and rs3811050, respectively, were significantly associated with an increased risk of AML, while rs3811051 showed no association. Four-locus haplotype analysis (rs3811046-rs3811047-rs3811050-rs3811051) demonstrated that T-A-C-G haplotype was associated a 2.47-fold increased risk of AML. SNP-SNP interaction analysis showed significant genetic interactions between rs3811046 and rs3811047, rs3811046 and rs3811050, and rs3811047 and rs3811050. Rs3811046 and rs3811047 did not affect IL37 gene expression. Some laboratory and clinical variables of AML may be influenced by IL37 and IL1F10 SNPs. In conclusion, rs3811046, rs3811047, and rs3811050 were associated with AML susceptibility in terms of allele, genotype, and haplotype, while rs3811051 showed no association. Three SNPs (rs3811046, rs3811047, and rs3811050) showed a significant gene-gene interaction.