Methylenetetrahydrofolate Reductase Gene C677T and A1298C Polymorphic Sequence Variations Influences the Susceptibility to Chronic Myeloid Leukemia in Kashmiri Population
Background: Methylenetetrahydrofolate reductase (MTHFR) gene is a crucial regulator of folate metabolism and its two prominent polymorphic variants C677T and A1298C lead to decreased MTHFR enzyme activity.Aim of the Study: We planned this case–control study based on numerous studies supporting the a...
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00612/full |
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| author | Shahid M. Baba Zafar A. Shah Khushboo Javaid Arshad A. Pandith Javeed Rasool Sajad A. Geelani Rafia A. Baba Shajrul Amin Gul Mohammad |
| author_facet | Shahid M. Baba Zafar A. Shah Khushboo Javaid Arshad A. Pandith Javeed Rasool Sajad A. Geelani Rafia A. Baba Shajrul Amin Gul Mohammad |
| author_sort | Shahid M. Baba |
| collection | DOAJ |
| description | Background: Methylenetetrahydrofolate reductase (MTHFR) gene is a crucial regulator of folate metabolism and its two prominent polymorphic variants C677T and A1298C lead to decreased MTHFR enzyme activity.Aim of the Study: We planned this case–control study based on numerous studies supporting the association of MTHFR polymorphisms (C677T and A1298C) with CML risk in different ethnic populations. Therefore, the influence of these polymorphisms on CML susceptibility was investigated among Kashmiri population (North India).Materials and Methods: Polymerase chain reaction/restriction fragment length polymorphism (RFLP) technique was employed for genotyping MTHFR C677T and A1298C SNP's in 125 CML patients as against 150 age and gender matched healthy controls.Results: A significant difference was observed in frequency of 677CT genotype between cases and controls [46.4 vs. 27.3% (p = 0.0005)]. Similarly combined 677CT+TT genotype showed significant difference between cases and controls [50.4 vs. 28.6% (p = 0.0002)]. Both MTHFR 677CT and 677CT+TT genotypes imposed greater than 2-fold risk of developing CML (OR = 2.4, 95%CI: 1.46–4.05; OR = 2.5, 95%CI: 1.53–4.16). In case of A1298C SNP, the frequency of 1298AC genotype was higher in controls (64.0%) as compared to CML cases (48.8%) (p = 0.04) and imparted a significant protective role from CML predisposition. Furthermore, haplotype analysis revealed only “677CT/1298AA” haplotype significantly increased the risk of CML predisposition [(p = 0.008) (OR = 3.2, 95% CI: 1.3–7.4)].Conclusion: We conclude that both MTHFR C677T and A1298C polymorphisms may be important genetic modifiers and seem to have a plausible role to confer risk of CML in Kashmiri population, where C677T SNP strongly increases the risk of CML while as A1298C SNP has a protective effect. |
| first_indexed | 2024-04-13T14:55:26Z |
| format | Article |
| id | doaj.art-80348a6e5e6f40b49d6ebac4a423e07a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T14:55:26Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-80348a6e5e6f40b49d6ebac4a423e07a2022-12-22T02:42:27ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-07-01910.3389/fonc.2019.00612457769Methylenetetrahydrofolate Reductase Gene C677T and A1298C Polymorphic Sequence Variations Influences the Susceptibility to Chronic Myeloid Leukemia in Kashmiri PopulationShahid M. Baba0Zafar A. Shah1Khushboo Javaid2Arshad A. Pandith3Javeed Rasool4Sajad A. Geelani5Rafia A. Baba6Shajrul Amin7Gul Mohammad8Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, IndiaDepartment of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, IndiaDepartment of Clinical Biochemistry, University of Kashmir, Srinagar, IndiaAdvanced Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, IndiaDepartment of Clinical Hematology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, IndiaDepartment of Clinical Hematology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, IndiaDepartment of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, IndiaDepartment of Clinical Biochemistry, University of Kashmir, Srinagar, IndiaDepartment of Medical Oncology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, IndiaBackground: Methylenetetrahydrofolate reductase (MTHFR) gene is a crucial regulator of folate metabolism and its two prominent polymorphic variants C677T and A1298C lead to decreased MTHFR enzyme activity.Aim of the Study: We planned this case–control study based on numerous studies supporting the association of MTHFR polymorphisms (C677T and A1298C) with CML risk in different ethnic populations. Therefore, the influence of these polymorphisms on CML susceptibility was investigated among Kashmiri population (North India).Materials and Methods: Polymerase chain reaction/restriction fragment length polymorphism (RFLP) technique was employed for genotyping MTHFR C677T and A1298C SNP's in 125 CML patients as against 150 age and gender matched healthy controls.Results: A significant difference was observed in frequency of 677CT genotype between cases and controls [46.4 vs. 27.3% (p = 0.0005)]. Similarly combined 677CT+TT genotype showed significant difference between cases and controls [50.4 vs. 28.6% (p = 0.0002)]. Both MTHFR 677CT and 677CT+TT genotypes imposed greater than 2-fold risk of developing CML (OR = 2.4, 95%CI: 1.46–4.05; OR = 2.5, 95%CI: 1.53–4.16). In case of A1298C SNP, the frequency of 1298AC genotype was higher in controls (64.0%) as compared to CML cases (48.8%) (p = 0.04) and imparted a significant protective role from CML predisposition. Furthermore, haplotype analysis revealed only “677CT/1298AA” haplotype significantly increased the risk of CML predisposition [(p = 0.008) (OR = 3.2, 95% CI: 1.3–7.4)].Conclusion: We conclude that both MTHFR C677T and A1298C polymorphisms may be important genetic modifiers and seem to have a plausible role to confer risk of CML in Kashmiri population, where C677T SNP strongly increases the risk of CML while as A1298C SNP has a protective effect.https://www.frontiersin.org/article/10.3389/fonc.2019.00612/fullMTHFRCMLBCR-ABLPCRKashmirIndia |
| spellingShingle | Shahid M. Baba Zafar A. Shah Khushboo Javaid Arshad A. Pandith Javeed Rasool Sajad A. Geelani Rafia A. Baba Shajrul Amin Gul Mohammad Methylenetetrahydrofolate Reductase Gene C677T and A1298C Polymorphic Sequence Variations Influences the Susceptibility to Chronic Myeloid Leukemia in Kashmiri Population Frontiers in Oncology MTHFR CML BCR-ABL PCR Kashmir India |
| title | Methylenetetrahydrofolate Reductase Gene C677T and A1298C Polymorphic Sequence Variations Influences the Susceptibility to Chronic Myeloid Leukemia in Kashmiri Population |
| title_full | Methylenetetrahydrofolate Reductase Gene C677T and A1298C Polymorphic Sequence Variations Influences the Susceptibility to Chronic Myeloid Leukemia in Kashmiri Population |
| title_fullStr | Methylenetetrahydrofolate Reductase Gene C677T and A1298C Polymorphic Sequence Variations Influences the Susceptibility to Chronic Myeloid Leukemia in Kashmiri Population |
| title_full_unstemmed | Methylenetetrahydrofolate Reductase Gene C677T and A1298C Polymorphic Sequence Variations Influences the Susceptibility to Chronic Myeloid Leukemia in Kashmiri Population |
| title_short | Methylenetetrahydrofolate Reductase Gene C677T and A1298C Polymorphic Sequence Variations Influences the Susceptibility to Chronic Myeloid Leukemia in Kashmiri Population |
| title_sort | methylenetetrahydrofolate reductase gene c677t and a1298c polymorphic sequence variations influences the susceptibility to chronic myeloid leukemia in kashmiri population |
| topic | MTHFR CML BCR-ABL PCR Kashmir India |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00612/full |
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