ABSTRACT
Warfarin, an oral anticoagulant is one of the most widely prescribed drugs in modern medicine. Large interindividuals variability due to age, gender, diet, concurrent drug interactions and variations in CYP2C9 and VKORC1 genes make the management of warfarin therapy challenging and yet no study has been conducted on the Bangladeshi population. The aim of the study was to identify the role of VKORC1 and CYP2C9 polymorphisms in Bangladeshi population in dose requirement of warfarin. We studied 87 heart valve replacement patients who were prescribed warfarin for minimum of 6 months with a target International normalized ratio of 2.0-3.5. Genotyping of VKORC1rs9923231 [-1639 G>A], CYP2C9[asterisk]2 and CYP2C9[asterisk]3 was performed by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism. The frequencies of GG, AG and AA genotypes of VKORC1rs9923231 in the studied population were 87.4%, 8%, and 4.6% respectively whereas the frequencies of the CYP2C9[asterisk]1/3 and CYP2C9[asterisk]3/3 were 4.6% and 3.4% respectively. The CYP2C9[asterisk]2 was not found in the studied population. The results of this study indicate that comparatively higher daily maintenance doses of warfarin were required to achieve the target INR for patients carrying both GG genotype of VKORC1rs9923231 and wild type variant of CYP2C9[asterisk]3 whereas minimum dose were required for patient having AA genotype of VKORC1rs9923231 and [asterisk]3/[asterisk]3 variant of CYP2C9
ABSTRACT
Objective: To verify possible associations between polymorphisms of glutathione S-transferase Mu (GSTM1), glutathione S-transferase θ (GSTT1) and glutathione S-transferase Pi (GSTP1) genes and susceptibility to lung cancer. Methods: A total of 106 lung cancer patients and 116 controls were enrolled in a case-control study. The GSTM1 and GSTT1 were analyzed using PCR while GSTP1 was analyzed using PCR-restriction fragment length polymorphism. Risk of lung cancer was estimated as odds ratio at 95% confidence interval using unconditional logistic regression models adjusting for age, sex, and tobacco use. Results: GSTM1 null and GSTT1 null genotypes did not show a significant risk for developing lung cancer. A significantly elevated lung cancer risk was associated with GSTP1 heterozygous, mutant and combined heterozygous+mutant variants of rs1695. When classified by tobacco consumption status, no association with risk of lung cancer was found in case of tobacco smokers and nonsmokers carrying null and present genotypes of GSTM1 and GSTT1. There is a three-fold (approximately) increase in the risk of lung cancer in case of both heterozygous (AG) and heterozygous+mutant homozygous (AG+GG) genotypes whereas there is an eightfold increase in risk of lung cancer in cases of GG with respect to AA genotype in smokers. Conclusions: Carrying the GSTM1 and GSTT1 null genotype is not a risk factor for lung cancer and GSTP1Ile105Val is associated with elevated risk of lung cancer.