Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population

Chronic myeloid leukemia is a hematopoietic stem cell disorder that causes uncontrolled proliferation of white blood cells. Although the clinical and biological aspects are well documented, little is known about individual susceptibility to this disease. We conducted a case-control study analyzing t...

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Bibliographic Details
Published in:	Genetics and molecular research Vol. 11; no. 2; pp. 1013 - 1026
Main Authors:	Lordelo, G S, Miranda-Vilela, A L, Akimoto, A K, Alves, P C Z, Hiragi, C O, Nonino, A, Daldegan, M B, Klautau-Guimarães, M N, Grisolia, C K
Format:	Journal Article
Language:	English
Published:	Brazil 01-01-2012
Subjects:	Adult Brazil Female Genetics, Population Glutathione Transferase - genetics Humans Leukemia, Myelogenous, Chronic, BCR-ABL Positive - enzymology Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics Male Methylenetetrahydrofolate Reductase (NADPH2) - genetics Polymorphism, Genetic Brazil
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Summary:	Chronic myeloid leukemia is a hematopoietic stem cell disorder that causes uncontrolled proliferation of white blood cells. Although the clinical and biological aspects are well documented, little is known about individual susceptibility to this disease. We conducted a case-control study analyzing the prevalence of the polymorphisms MTHFR C677T, MTHFR A1298C, del{GSTM1}, del{GSTT1}, and haptoglobin in 105 patients with chronic myeloid leukemia (CML) and 273 healthy controls, using PCR-based methods. A significant association with risk of developing CML was found for MTHFR 1298AA (odds ratio (OR) = 1.794; 95% confidence interval (CI) = 1.14-2.83) and GSTM1 non-null (OR = 1.649; 95%CI = 1.05-2.6) genotypes, while MTHFR 1298AC (OR = 0.630; 95%CI = 0.40-0.99) and GSTM1 null (OR = 0.606; 95%CI = 0.21-0.77) genotypes significantly decreased this risk. There appeared to be selection for heterozygosity at the MTHFR 1298 locus. The considerable range of variation in this and other human populations may be a consequence of distinctive processes of natural selection and adaptation to variable environmental conditions. The Brazilian population is very mixed and heterogeneous; we found these two loci to be associated with CML in this population.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1676-5680 1676-5680
DOI:	10.4238/2012.April.19.6