| Acute myeloid leukemia (AML) is a complex hematological neoplasm with poor prognosis. At
present, overwhelming evidence indicates that different genetic abnormalities are relevant to the
pathogenesis of AML. Nevertheless, its exact molecular mechanism is still unknown. Recently, it
was reported that lncRNAs play crucial roles in tumorigenesis. But, their role in the molecular
pathogenesis of AML has not been extensively explored. GAS5, one of the earliest known
lncRNAs, has an essential role in the formation and progression of multiple human cancers. It
was recently demonstrated that GAS5 acts as a riborepressor of the Glucocorticoid receptor )GR)
and abnormal levels of GAS5 may alter response of hematopoietic cells to glucocorticoids.
GAS5 can have interaction with the GR that encoded by NR3C1 gene and inhibit its
transcriptional activity.
To test whether the genetic variants can be associated with AML risk, we genotyped rs55829688
(T>C) polymorphism in GAS5 and three NR3C1 SNPs namely rs6195, rs41423247 and
rs6189/rs6190 in a population of 100 Iranian AML patients and 100 healthy subjects.
The analysis of the data showed the frequency of alleles and genotypes of rs55829688 and
rs6189/rs6190 polymorphisms did not differ between patients and healthy subjects. But,
rs41423247 and rs6195 demonstrated a significant correlation with AML risk. The rs6195 was
associated with higher AML susceptibility in the co-dominant (OR=4.58, 95% CI=2.11-9.981,
P<0.0001), dominant (OR=4.55, 95% CI=2.155-9.613, P<0.0001), and over-dominant
(OR=4.43, 95% CI=2.042-9.621, P<0.0001) models. Also, the rs41423247 polymorphism was
associated with higher risk of AML in co-dominant (OR=2.07, 95% CI=1.171-4.242, P=0.012)
and dominant (OR=2.47, 95% CI=1.192-5.142, P=0.010) models. Furthermore, haplotype
analysis (rs41423247, rs6189.rs6190, rs6195, and rs55829688 respectively) demonstrated that
GGAT, CGGT, and GGGT haplotypes were associated with higher risk of AML in the studied
population (p-values= 0.007, 0.042 and 0.044, respectively). The present study reveals a possible
role for NR3C1 in the pathogenesis of AML. |