Genetic Polymorphism of the immune response in humans: studies by genotyping and gene expression analysis

Abstract

This study aims to analyse human genomic variability in a systematic way in order to identify genetic risk for multifactorial diseases and also evaluate its functional impact in a more individualized form. 1) a new family of genes called MIC was recently identified (MHC Class I Chain-related). MICA and MICB located next to the HLA-B locus, are functional and exhibit special biological characteristics. To this date 49 alleles for MIC-A and 11 MIC-B alleles have been described. Expression of these molecules is induced by cellular stress, and has been shown in normal and tumoral epithelial cells, in endothelium and in many others. To evaluate the importance of MIC in immune response we will compare allele distribution in a sample of the normal São Paulo population with patients with Behçet disease, besides measuring MIC-A gene expression in epithelial cell lines from different tumor stages; 2) in a second project we will analise the role of genetic polymorphism of cytokines involved in immune response to disease comparing functional and clinical data with SNP genotyping and gene expression of candidate genes by RT -PCR and microarray analysis in Chagas' disease cardiomyopathy, Rheumatic Heart Disease and chronic rejection in kidney and heart transplant patients, ali are major research projects in our laboratory. Due to the nature of these studies and the quantity of information already at hand, it will be necessary to obtain and classify genetic data referring to normal individuals, in order to integrate information into the DNA bank of the laboratory. (AU)