The Study Of Genetic Polymorphisms And β-lactam Allergy

Aim:Adverse drug reactions in clinical medical cause enormous harm, which is mainly caused by individual difference drug reactions. This difference is due to genetics, environment, disease state, diet structures and many other factors. Genetic polymorphism, which involved in the mechanisms of drug effect of the individual differences is a common factor and unable to control. Understanding and clarifing the individual differences in adverse drug reactions and the mechanisms of drug effect between groups and individual are important issues to improve the efficacy and quality of human life.Material and Methods:we randomly selected two groups of patients with and without drug allergy against β-lactam and conduct a correlation of SNPs and β-lactam allergy with a case-control method. Blood samples were collected and used for this study. Microarray technology was used for genotyping and searching for various mononucleotide polymorphisms related to the activities of β-lactam allergy, for example, some cytokines and their receptors such as IL-21R、 IL-10、IL-13、IL-4Rα、Fc-Riβ、IFNGR2 and CYP3A4. Identify the relationship between these various genes polymorphisms and β-lactam allergy. Haplotypes were reconstructed using the SHEsis.Results:Investigate the IL21R rs943154, IL21R rs2285452, IL-10 rs1800871, IL-10 rs1800872, IL-10 rs1800896, IL-13 rs20541, IL-13 rsl881457, IL-13 rs1800925, IL-4Ra rs1801275, Fc-Rip rs569108, IFNGR2 rs9808753 and CYP3A4 rs2242480 polymorphisms by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods or SNP chip method to detect candidate genes mutations and find relationship between SNPs and β-lactam allergy. Evaluate the SNPs in the patients of β-lactam allergy with SPSS 17.0 statistical methods. The results showed that IL-21R rs963154 and rs2285452 polymorphism have no significant correlation with β-lactam allergy in northwest Chinese, so do rs1800871, rs1800896, rs20541, rsl881457, rs1800925, rs1801275, rs569108 and rs9808753 polymorphisms (p>0.05). The CYP3A4 rs2242480 genotype has significant correlation with β-lactam allergy in northwest Chinese. The CT genotype is a protective factor in male patients of P-lactam allergy, P value is 0.022, OR value is 0.167 (0.032-0.867).The haplotypes have no significant correlation with β-lactam allergy in Chinese.Conclusion:The CYP3A4 rs2242480 genotype has significant correlation with β-lactam allergy in northwest Chinese. The CT genotype is a protective factor in male patients with β-lactam allergy, there is not relevance between β-lactam allergy and other candidate gene mutations. The above results provide ideas for the mechanism of β-lactam allergy, and also provide important clues and basis for Individual therapy in the near future.