A Proteogenomic Analysis of Haptoglobin in Malaria

Haptoglobin (Hp), an acute phase inflammatory protein has been associated with malaria pathogenesis in several proteomics studies. The gene has two co-dominant alleles: Hp1 and Hp2 that produce three genotypes: Hp1/Hp1, Hp1/Hp2 and Hp2/Hp2. In this study, we perform validation of the proteomics data with Multiple Reaction Monitoring Mass Spectroscopy (MRM-MS). We further analyze the association of the Hp gene variants with severe, non-severe malaria and community (healthy) controls using genotyping PCRs and DNA sequencing. We find highly significant values of Hp in the MRM assay that showed a correlation with severity of malaria and were clearly distinguished from another febrile disease, dengue. We also find the Hp2/Hp2 genotype in non-severe malaria patients (74%) and community controls (72%) while patients diagnosed with severe malaria showed only (31%) of this genotype. Sequencing of the Hp promoter region revealed three SNPs along with 10 unique haplotypes, out of which five were associated with non-severe and three with severe malaria populations (X2 = 130; df = 18; p < 0.0001). This proteo-genomic study focuses on the correlation of the Hp protein and gene with malaria, highlighting the pivotal role of this acute phase immune gene in malaria pathogenesis. This article is protected by copyright. All rights reserved