4 research outputs found
Study of IRF-8 gene in Kashmiri population and its relation with Chronic Myeloid Leukemia
Chronic myelogenous leukemia (CML) is a clonal hematopoietic disorder caused by an
acquired genetic defect in a pluripotent stem cell. A number of theories have been
postulated to describe the etiology of CML such as genetic alterations and alterations in
cytokine production. A combination of inflammatory cytokines have an important role
in cancer development. The aim of this study was to screen for mutations of IRF-8 gene
in CML cases and healthy controls of the Kashmiri population. We included eighty
confirmed CML cases and an equal number of age, district and gender matched controls
in this study. HaeIII enzyme digestion cuts amplified product at 5β-GGCC-3β sequence
and any mutation in it abrogates restriction digestion by this enzyme. Restriction results
showed wild conditions with no mutation at any of the 6 positions where HaeIII cuts,
which was confirmed by the sequencing results as well. Further sequencing results
showed interesting single G A substitution at position 92 of the amplified product. In
CML cases, the allelic frequency for normal allele (G) was found to be 47.5% (76/160)
and the allelic frequency observed for G A type was found to be 52.5% (84/160). The
allelic frequency observed in controls for normal allele (G) was 91.25% (146/160). The
frequencies analyzed for G A allele was 8.75% (14/160). Since the frequency
observed for G A allele was higher in CML cases (52.5%) than in normal controls
(8.75%) and it was found to be statistically significant (OR= 11.52, 95%CI: (6.13-21.6);
p = 0.001). Sequencing results further showed occasional deletion at the same position
where transition was seen. Also we found that CML is prevalent more in males as
compared to females (ratio is 1:1.12). Majority of the CML case were from district
Srinagar of the Valley. Mean age of the cases and controls were found to be 44.7 years
and 43.6 years respectively. We observed a higher representation of CML cases in the
age group between 30 and 40. Furthermore, the presence of the Philadelphia
chromosome (BCR-ABL fusion gene) was observed in 82.5% of CML cases in our
study. This is the first report of the sequence variation in exon 7 region of IRF-8 gene
and the risk to CML in the Kashmiri population. However, more insight need to be
gained and further substantiated by conducting a similar study on statistically
significant sample size