Abstract Background IL4 is a versatile cytokine essentially known for differentiation, proliferation, and cell death in cells. Its dysregulation has been found to be associated with the development of inflammatory disorders. Objective The goal of the current investigation is to identify and select non-synonymous single nucleotide polymorphisms (nsSNPs) in the IL-4 gene by employing computational methods which may have a potential functional impact on the occurrence of disease. Method & Result Six different nsSNPs were predicted to be deleterious based on the consensus of different algorithms: SIFT, Polyphen2 (Humdiv and HumVar), PredictSNP, and SNP&GO.I-mutant and MuPro assessment revealed a decrease in the stability of these mutants except K150M. Modelling was then carried out to build the wild-type along with its mutants, followed by superimposition of the wild-type with mutants to evaluate the RMSD value, which lies between 0.26-0.34. Simulation results of mutant models, along with wild-type, showed that four of the mutants (N113Y, A118G, R109W, and K150M) deviated most and were unstable. A118G showed a significant deviation from the wild-type, while V53A and C123R were stable. Conclusion The finding establishes the evidence that the identified six nsSNPs of IL-4 can be the new entrant presenting their candidature for genetic testing.

Abstract Aims: SLC transporters are expressed in lungs and are essential membrane proteins responsible for the transport of wide range of chemotherapeutic drugs. Polymorphisms in SLC19A1, SLCO1B1, and SLCO1B3 gene in North Indian lung cancer patients are investigated. Methods: A total of 610 lung cancer patients undergoing platinum-based chemotherapy were recruited in the study. Polymorphisms of SLC19A1 (G80A), SLCO1B1 (A388G, T521C) and SLCO1B3 (A1683-5676G) in North Indian lung cancer patients were assessed and statistical analysis were carried out. Results: Our data revealed that patients harboring mutant genotype (AA) for SLC19A1 G80A polymorphism had higher MST as compared patients with wild type (GG) genotype (MST=9.33 versus 8.23). ADCC patients with mutant genotype (AA) showed better survival outcomes for SLC19A1 G80A (MST=9.4 versus 8.8, HR=0.6; p=0.04). In SCLC, SLC19A1 G80A polymorphism revealed increased survival in the patients harboring mutant genotype (AA) (MST=9.6 months versus 7.6 months, p=0.04). For SLCO1B3 polymorphism, patients administered with carboplatin/cisplatin and docetaxel showed inferior survival outcomes in subjects carrying heterozygous alleles (AG) (MST=2.9 months versus 9.6 months, p=0.006, HR=14.01). For anemia, SLCO1B1 T521C showed that patients with heterozygous genotype (TC) had a reduced risk of developing anemia (OR=0.44, 95% CI=0.20-0.96; p=0.04). Patients with SLCO1B1 A388G polymorphism harboring AG alleles was associated with a lower incidence of thrombocytopenia (OR=0.41, 95% CI=0.20-0.82; p=0.01). Patients with heterozygous (AG) genotype (OR=0.35, 95% CI=0.17-0.72; p=0.002) for A1683-5676G polymorphism showed lower incidence of nephrotoxicity. Conclusion: Genotyping of SLC polymorphism is crucial for predicting survival and toxicity in lung cancer patients undergoing platinum-based chemotherapy.