No abstract

No abstract

There is a great range in outcomes after mycobacterial infections, and this is probably due to individual variation in immune responses. One of the key cytokine regulators of the immune response is interleukin (IL-) 12. The IL12B gene encodes the p40 chain of both IL-12 and IL-23 and it has two major variant sites at which different alleles are associated with increased levels of gene expression and with susceptibility to a range of immune-related diseases. We hypothesized that IL12B variants associated with increased expression would be as associated with susceptibility to persistent mycobacterial infection. We tested this hypothesis by genotyping Indian subjects, having either leprosy or tuberculosis (TB), as well as ethnically matched controls. Subjects with leprosy were less likely to have the 3'UTR genotype associated with lower IL12B expression (P= 0.001). Subjects with TB were not only more likely to have the high-expressing IL12B promoter genotype (P= 0.01) but also more likely to have this in the same haplotype with the high expressing 3'UTR allele (P= 0.0009). These results suggest these infectious diseases may be improved by modulating IL-l2p40 production.

The allelic and genotype frequencies corresponding to 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes interleukin (IL) 1-alpha (T/C -889), IL1-beta (C/T -511, T/C +3962), IL12 (C/A -1188), interferon-gamma (A/T UTR 5644), transforming growth factor-beta (C/T codon 10, G/C codon 25), tumour necrosis factor-alpha (G/A -308, G/A -238), IL2 (T/G -330, G/T +160), IL4 (T/G -1098, T/C -590, T/C -33), IL6 (G/C -174, G/A nt 565), IL10 (G/A -1082, C/T -819, C/A -592), IL1R (C/T pst11970), IL1RA (T/C mspa111100) and IL4RA (G/A +1902) were determined in 130 healthy North Indian subjects. All genomic typings were performed with polymerase chain reaction with sequence-specific assays. An analysis of the allelic and haplotype frequencies in the North Indian population showed a good fit with the Hardy-Weinberg equilibrium for most of the SNPs. The data can be used for anthropological comparisons, as well as for association studies with different diseases and for use in transplant situations involving acute and chronic rejection.

Selection of an HLA identical donor is a critical pre-requisite for successful hematopoietic stem cell transplantation (HSCT). Most transplant centers utilize blood as the most common source of DNA for HLA testing. However, obtaining blood through phlebotomy is often challenging in patients with conditions like severe leucopenia or hemophilia, pediatric and elderly patients. We have used a simple in-house protocol and shown that HLA genotypes obtained on DNA extracted from saliva or hair are concordant with blood and hence can be used for selection of donors for HSCT or organ transplantation. Similarly, for post-HSCT chimerism monitoring, non-availability of pre-transplant DNA samples poses a major limitation of reference STR fingerprints. This study shows that DNA obtained post-HSCT from hair follicles can be used to generate pre-transplant patient specific fingerprints while the STR profiles obtained in saliva samples cannot as these display a mixed state of chimerism.