ABSTRACT
Background: Methotrexate (MTX) blocks MethyleneTetrahydrofolate Reductase (MTHFR) Enzymethereby, interrupt folate metabolism, it is used in thetreatment of cancer and autoimmune disorders. Aimand Objectives: The present study aimed to evaluatethe relationship of the MTHFR polymorphisms withserum MTX concentration and its toxicity in AcuteLymphoblastic Leukemia (ALL) patients treated withhigh dose MTX infusion. Material and Methods: Levelof Serum MTX was measured, along with the detectionof MTHFR polymorphisms viz. C677T and A1298Cby Polymerase Chain Reaction (PCR) followed byDNA sequencing. The percentages of toxicitydeveloped in patients were calculated among the wildtype and carriers for both polymorphisms and werecompared between the groups. Results:The majority ofpatients 36 (72 %) were wild type for the C677Tpolymorphism and 32 (64 %) of patients were carriersfor the A1298C polymorphism [48% heterozygous(AC), and 16 % homozygous (CC)]. Among 50 ALLpatients studied, significant difference was noted in thegenotype and allele frequencies for C677Tpolymorphism, while only allele frequencies differedsignificantly for A1298C polymorphism. The serumMTX level at 48 hours after the start of High DoseMTX (HDMTX) infusion of the C677T variant (CT)was slightly high in all four cycles however, in the firstcycle, there was a significant increase in the level ofMTX. There was no significant difference in the serumMTX level found in all four cycles between patientswild type and carriers for A1298C polymorphism. ForA1298C polymorphism, the mean SGPT level incarriers was significantly high as compared to wildtype. Conclusion: The present study concludes thatpatients with C667T variant had elevated serum MTXconcentration at 48 hours after the start of HDMTXinfusion.
ABSTRACT
Background: Diabetes Mellitus (DM) is one of theleading non-communicable disorders, leading tovarious complications viz. cardiovascular diseases,retinopathy, nephropathy, neuropathy and peripheralvascular disorders. Diabetic Nephropathy (DN)patients further develop into End Stage Renal Disease(ESRD) and they have to undergo the repeated bloodtransfusions, increasing the social and economicburden. The number of risk factors are known forcausation of diabetic nephropathy including theenvironmental, biochemical as well as genetic factors.The association of nephropathy with various genes hasbeen proved. Aim and Objectives: In the present studywe attempted to check the association ofInsertion/Deletion (I/D) polymorphism of AngiotensinConverting Enzyme (ACE) in diabetic patients withand without nephropathy and also with thebiochemical markers. Material and Methods: Eachgroup consisted of 110 individuals viz. diabetics withand without nephropathy and age and gender matchedhealthy controls. Results: The determination of I/Dpolymorphism by polymerase chain reaction revealedthe significant increased 'D' allele frequencies inpatients of diabetes with and without nephropathy thanthe controls, while no significant difference was notedin genotype frequencies. The odds ratios for thispolymorphism were calculated to be 1.84 and 2.41 forDM and DN respectively in comparison with thehealthy controls. The regression analysis indicated I/Dpolymorphism is associated positively with all thelipid parameters, except High Density LipoproteinCholesterol (HDL-C) which was negatively associatedwith the polymorphism. The levels of lipid parameterswere also significantly increased in patients of diabeteswith and without nephropathy carriers for 'D' allelethan the patients having 'I' allele, while the level ofHDL-C was significantly decreased. Conclusion: Theconclusion can be made from these results that, thepresence of I/D polymorphism of ACE may increasethe risk of development of nephropathy in generalpopulation, with the role of 'D' allele in its causation,along with its effect on the biochemical markers.