Cancer is a complex disease and the genetic susceptibility to it could be an outcome of the inherited difference in the capacity of xenobiotic metabolizing enzymes. Glutathione-S-transferases (GSTs) are phase II metabolizing enzymes whose various genotypes have been associated with increased risk of different types of cancer. Null mutations caused by the deletion of the entire gene result in the absence of the enzymatic activity and increase in the risk of developing cancer including chronic myeloid leukaemia (CML). In the present case-control study we evaluated the effect of null mutations in GSTM1 and GSTT1 genes on the risk of developing CML. The study included 75 CML patients (43 males and 32 females; age (mean ± S.D) 42.3 ± 13.4 years) and unrelated non-malignant controls (76 male and 48 females; age (mean ± S.D) 41.5 ± 12.9). The distribution of GSTM1 and GSTT1 genotypes in CML patients and controls was assessed by multiplex-PCR method. Logistic regression was used to assess the relationship between GSTM1 and GSTT1 genotypes and risk of CML. Chi-square test was used to evaluate the trend in modulating the risk to CML by one or more potential high risk genotype. Although GSTM1 null genotype frequency was higher in CML patients (41%) than in the controls (35%), it did not reached a statistical significance (OD = 1.32, 95% CI: 0.73-2.40; P value = 0.4295). The frequency of GSTT1 null genotypes was higher in the CML patients (36%) than in the controls (21%) and the difference was found to be statistically significant (OD = 2.12, 95% CI: 1.12-4.02; P value = 0.0308). This suggests that the presence of GSTT1genotype may have protective role against the CML. We found a statistically significant (OD = 3.09, 95% CI: 1.122-8.528; P value = 0.0472) interaction between the GSTM1 and GSTT1 null genotypes and thus individuals carrying null genotypes of both GSTM1 and GSTT1 genes are at elevated risk of CML.
Background & objectives:Psoriasis is a chronic inflammatory skin disease with unknown aetiology. So far studies have confirmed that interleukins, pro-inflammatory factors and T-cell activation play major role in the development of disease. Interleukin-17 (IL-17) a T helper inflammatory cytokine, was found to be positively correlated with severity of psoriasis. However, the specific mechanism has not been clarified. IL-17A and IL-17F are group members of IL17 family cytokines and found to be located adjacent to one another on the same human chromosome, 6p12. The present study was designed to identify the association between IL-17A and IL-17F gene polymorphism with susceptibility of psoriasis in north Indian population.Methods:A total of 166 psoriasis patients and 150 healthy controls were genotyped for IL-17A and IL-17F gene polymorphism by amplification refractory mutation system-polymerase chain reaction method. One single nucleotide polymorphism (SNP) was analysed in IL-17A (rs10484879) and one SNP in IL-17F (rs763780) to look for an association with psoriasis.Results:Our study indicated decreased frequency of IL-17A (rs10484879) G allele (51.8 vs. 65.0%), and IL-17F (rs763780) C allele (36.5 vs. 45.7%) in psoriatic patients as compared to healthy controls.Interpretation & conclusions:The present findings suggest that IL-17A (rs10484879) G/T and IL-17F (rs763780) C/T gene polymorphisms may contribute in pathogenesis of psoriasis. Further studies need to be done to confirm these findings.
Background:
IL-10 is an important pleiotropic, immunoregulatory and anti-inflammatory
cytokine which plays a significant role in the pathogenesis of psoriasis.
Objective:
The aim of the present study was to determine whether the three polymorphic sites of the
IL-10 gene, haplotype and serum level confer susceptibility to psoriasis.
Method:
200 psoriatic patients and 200 controls were genotyped for three IL-10 polymorphic sites by
ARMS polymerase chain reaction. Serum levels of IL -10 were measured by ELISA.
Results:
Our results demonstrated that polymorphism of IL-10 -592 C/A (adjusted* OR = 9.25; 95%
CI =3.16- 27.06) and IL-10 1082 A/G (adjusted* OR = 4.28; (95% CI =1.46- 12.56) was found to be in
association with increased risk of psoriasis while as IL- 10 819 C/T (adjusted* OR= 1.60; (95% CI =
0.65-3.95) polymorphism does not show any significant association with the risk of psoriasis. HT7
GTC haplotype is associated with increased risk of psoriasis. Serum levels of IL-10 were found to be
significantly low in patients, as compared to controls with a non-significant correlation between serum
IL-10 level and psoriasis severity.
Conclusion:
IL-10 polymorphism imparted significant risk towards the development of psoriasis in
North Indian population. Highlighting the role of IL-10 cytokine in the pathogenesis of psoriasis will
help in the development of psoriasis management.
Human Cytochrome P 450 3A, a variant of Cytochrome P-450-dependent monooxygenases is a major drug metabolizing enzyme. CYP3A has evolved to catalyze the biotransformation of its substrate. A great deal of inter-individual variation in expression levels exists for CYP3A5 gene. The common polymorphism in CYP3A5 that induces a cryptic splice site has been shown to cause a significant reduction in its expression. Variation in CYP3A enzyme activity contributes greatly to variation in systemic clearance of CYP3A substrates and its oral bioavailability. The present study was designed to study the CYP3A5*3 polymorphism in the Kashmiri population. CYP3A5*3 genotypic status of 400 unrelated individuals of the Kashmiri population wasevaluated by PCR-RFLP method. The frequency of CYP3A5 variant in Kashmiri population was found similar to Caucasian but higher than that in Chinese and Japanese population. Our finding suggest that approximately 89.5% of study population carry CYP3A5*3 genotype and thus might be at an increased risk. So, detection of CYP3A5 variant alleles and knowledge about their allelic frequency in ethnic Kashmiris might play a key player in improved therapeutic intervention in Kashmiri population.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.