Evidence map›Paper›PMID 34530993›Full record

ArticleGene2019

Influence of Caspase-9 polymorphisms on the development of Chronic Myeloid Leukemia- A case-control study.

Prajitha Mohandas Edathara, Manjula Gorre, Sailaja Kagita, Anuradha Cingeetham, Sandhya Annamaneni, Raghunadharao Digumarti, Vishnupriya Satti

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Article in Gene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Prajitha Mohandas EdatharaDepartment of Genetics, Osmania University, Hyderabad, Telangana, India.
Manjula GorreDepartment of Biochemistry, Osmania University, Hyderabad, Telangana, India.
Sailaja KagitaHomi Bhabha Cancer Hospital and Research Centre, Visakhapatnam, Andhra Pradesh, India.
Anuradha CingeethamJawaharlal Nehru Technological University (JNTU), Hyderabad, Telangana, India.
Sandhya AnnamaneniDepartment of Genetics, Osmania University, Hyderabad, Telangana, India.
Raghunadharao DigumartiHomi Bhabha Cancer Hospital and Research Centre, Visakhapatnam, Andhra Pradesh, India.
Vishnupriya SattiDepartment of Genetics, Osmania University, Hyderabad, Telangana, India. Electronic address: sattivishnupriya@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionChronic Myeloid Leukemia (CML) is a myeloproliferative disorder, characterized by the overproduction of myeloid cells in all stages of maturation. It is usually defined by three sequential stages (Chronic, Accelerated and Blast-crisis) where the transition from chronic to accelerated to blast phases is presumed to occur due to secondary genetic changes, viz. accumulation of mutations, activation of downstream pathways and failure of apoptosis. Caspase 9 is the initiator caspase involved in mitochondrial-mediated apoptotic pathway. Polymorphisms in the promoter (-1263 A>G, -712C>T, -293 del) and coding (Ex5 +32G>A) regions of CASP9 gene are found to influence the expression levels by either impairing the activation or loss of expression of CASP9 or insufficient formation of apoptosome.

methodsThe present case-control study was carried out on 999 individuals, comprised of 485CML cases reported at Nizams Institute of Medical Sciences (NIMS), Hyderabad and 514 age and gender-matched healthy individuals from local population. DNA was isolated by non-enzymatic/salting-out method and was genotyped using RFLP technique.

resultsIt was observed that the presence of G allele of CASP9 -1263A>G polymorphism enhanced the risk for CML while CASP9 -712C>T and CASP9 -293del SNPs conferred protection against development of CML. Haplotype analysis of promoter and exonic polymorphisms had revealed increased risk associated with two haplotypes G_C_del (+)_G (OR-1.61, 95% CI-0.97-2.65, p-0.06#) and G_C_del (-)_G (OR-2.09, 95% CI-0.94-4.66, p-0.07#) suggesting the role of G allele of CASP9 -1263A>G in conferring risk independent of other SNPs. Pairwise LD analysis performed for all the four SNPs revealed the presence of LD among the SNPs.

conclusionThe results of the present study therefore concludes the role of CASP9 -1263A>G polymorphism in increasing the risk for the development and progression while CASP9 -712C>T and CASP9 -293del SNPs conferred protection and CASP9 Ex5 +32G>A was involved in conferring resistance which could be in combination with other SNPs or factors affecting them.

Indexed as

ApoptosisCaspase 9 polymorphismsChronic Myeloid LeukemiaHaplotypeRFLP

Identifiers

PMID34530993
PMCPMC7286081

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