Regulatory Genetic Variation at the S100B Gene Associates with Vaso-Occlusive Manifestations in Sickle Cell Disease

In sickle cell disease (SCD) polymerization of hemoglobin S under deoxygenated conditions causes vaso-occlusion, which can manifest as acute pain crisis and progressive bone/organ damage. Molecular studies have attributed vaso-occlusion to elevated vascular adhesion and inflammatory responses, whereas the genetic regulation has only recently been assessed.Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) was hybridized to Illumina Human 610-Quad SNP array for the PUSH and Walk-PHaSST cohorts and to Affrymetrix SNP 6.0 array for the Howard SCD expression cohort. Single nucleotide polymorphisms (SNPs) for 381 PUSH, 525 Walk-PHaSST, and 55 Howard patients were imputed to 1000 genomes project phase 3 data. Messenger RNA from PBMCs was profiled using Affymetrix Human Exon 1.0 ST Array for the Howard expression cohort and Affymetrix Human gene 2.0 ST array for the UIC expression cohort.Patients within the PUSH and Walk-PHaSST cohorts were classified to four groups according to a cumulative pain score, calculated based on pain frequency and questionnaire description of pain intensity. Pain grouping was examined for correlation with other SCD complications using Cochran Armitage test. History of acute chest syndrome (ACS, PUSH P=3.8x10-9, Walk-PHaSST P=2.4x10-5) and avascular necrosis (AVN, PUSH P=4.1x10-4, Walk-PHaSST P=3.7x10-5) were the most significant clinical manifestations that consistently associated with pain in the two cohorts.To investigate the genetic c...
Source: Blood - Category: Hematology Authors: Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Poster I Source Type: research