ABSTRACT
Little is known about the susceptibility to acute myeloid leukemia. We aim to search non-protein coding regions of key hematopoiesis transcription factors for genetic variations associated with acute myeloid leukemia susceptibility. We genotyped SNPs of RUNX1 P1 promoter, P2 promoter, +23 enhancer, intron 5.2 enhancer, PU.1 promoter, CEBPA promoter, and CEBPE promoter from acute myeloid leukemia patients and healthy controls. Rs2249650 and rs2268276 at RUNX1 intron 5.2 enhancer were found to be associated with acute myeloid leukemia susceptibility. Artificial reporters containing different rs2249650 and rs2268276 alleles showed differential activities in the K562 cell line, a human immortalized myeloid leukemia line. Rs2249650 contributes to reporter activities more than rs2268276. Gel shift assay is consistent with the luciferase assay. Supershift assay indicated that one potential binding protein was PU.1. To sum up, rs2268276 and especially rs2249650 may be qualified as new acute myeloid leukemia susceptibility-associated SNPs.
Subject(s)
Core Binding Factor Alpha 2 Subunit/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Leukemia, Myeloid, Acute/genetics , Polymorphism, Single Nucleotide , Untranslated Regions , Adult , Aged , Alleles , Base Sequence , Case-Control Studies , Cell Line, Tumor , Female , Gene Frequency , Genotype , Humans , Leukemia, Myeloid, Acute/diagnosis , Male , Middle Aged , Odds RatioABSTRACT
This study aims to examine whether the presence of polymorphisms in TNF-α (rs361525 and rs1799724) and MTHFR (rs1476413 and rs9651118) genes is associated with the pathogenesis of cerebral palsy (CP). A total of 105 CP patients and 114 age-, gender-, and ethnicity-matched healthy controls were genotyped for the selected polymorphisms, using TaqMan allelic discrimination assay. Odds ratios (OR) and 95 % confidence intervals (CI) were determined to measure the strength of associations of TNF-α and MTHFR polymorphisms with CP. The proportion of subjects with the gestational age more than 37 weeks or asphyxia was much larger in cases compared with controls (gestational age 63.8 vs. 34.2 %; asphyxia 25.7 vs. 7.9 %). The genotype frequencies of TNF-α rs1799724 were similar between groups (P > 0.05), yet the allele distributions were significantly different (P < 0.05). Both the allele and genotype distributions of MTHFR rs9651118 polymorphism varied significantly between the groups (P < 0.05). Subgroup analysis based on gestational age indicated a significant association between rs361525 and rs9651118 and CP with or without premature. TNF-α protein concentrations were significantly increased among patients with rs361525 GG genotype compared with controls. Also, a significant increase in the risk of CP was observed to be associated with the interactions of TNF-α rs1799724 and MTHFR rs9651118 (OR 2.75, 95 % CI 1.23-6.13). These data suggest that polymorphisms in TNF-α and MTHFR genes might be involved in the pathogenesis of CP in Chinese infants.
