Manmohan Pandey

Introduction: This is a first study where user friendly software (MASS KIR Analyzer) has been presented to analyze the Killer Immunoglobulin-like receptors (KIR) gene content diversity. The main objective of this software is to generate error free KIR genotyping data. Materials and Methods: The MASSKIR Analyzer accepts KIR genotyping data in binary format. It has the potential to determine KIR genotype, haplotype and linkage group frequencies and assignment of genotypic ID for each KIR profile as suggested by the Allele Frequency Net database. The software includes linkage disequilibrium analysis based on Lewontin, Mattiuz and Cramer’s V statistic’s principle. Genotype, haplotype and linkage group modules of the software were validated based on KIR genotyping data (n=12,481) available at the Allele Frequency Net database. Genetic distance and heatmap modules of the software were validated based on KIR data (n=976) from the Human Genome Diversity Project-Centre d'Etude du Polymorphisme Humain (HGDP-CEPH) database. Results: The MASS KIR Analyzer software detected 225 genotypic errors in the KIR dataset reported to the Allele Frequency Net database. The Linkage Disequilibrium analysis revealed negative linkage disequilibrium between KIR3DS1-3DL1(p=<0.001) and KIR2DL2-2DL1(p=<0.001) genes and positive linkage disequilibrium between KIR2DS2-2DL2 (p=<0.001) genes. Genetic distances calculated for the HGDP-CEPH KIR populations, revealed similar results in lieu of published data for clustered heatmap. This validated proper functioning of the software for KIR data analysis. Conclusion: The MASSKIR Analyzer is a promising software for KIR biologists and may significantly improve the KIR genotyping without errors.

Malnutrition inflammation syndrome (MIS) is common among ESRD patients. In the present study, we have investigated the association of genetic markers associated with appetite and energy regulation with malnutrition inflammation syndrome among end-stage renal disease (ESRD) patients. Two hundred and fifty-seven patients on maintenance hemodialysis and 200 normal healthy controls were included in the study. Nutritional assessment was done by subjective global assessment scores (SGA). Genotyping of leptin-2548 G/A (rs7799039), ghrelin Leu72Met (rs696217-408 C/A), Arg51Gln (rs34911341-346 G/A) and uncoupling protein 2 (UCP2) 45 bp insertion deletion was done using PCR–RFLP. Levels of leptin and acyl ghrelin were assessed using ELISA. Leptin-2548 AA genotype was associated with twofold higher risk of disease susceptibility while UCP2 insertion–deletion heterozygotes showed protective effect. Ghrelin Gln51Gln and Met72Met genotype were associated with 3.4- and 2.5-fold higher disease susceptibility. The Met72 and Gln51 allele showed 3.3- and 2.1-fold higher susceptibility to malnutrition in severe SGA group. Further, the levels of acyl ghrelin were significantly less in severe category of malnutrition and in poor appetite group. On combined analysis, the group 2 (presence of 3–4 risk alleles) showed 1.5- and twofold higher susceptibility to disease and malnutrition, respectively. On docking analysis, it was observed that higher receptor binding energy was associated with the mutant form of ghrelin (Gln51). Moderate and severe SGA were associated with 2.2- and 4.1-fold higher death hazard. Our study suggests that ghrelin may be major marker contributing to susceptibility to MIS among ESRD patients.