Severity of hypoxic ischemic encephalopathy correlates with increased expression of angiogenin in neonates.

BACKGROUND: Angiogenin is a small protein encoded by the ANG gene. It is activated by tissue hypoxia, and is known to be a potent stimulator of angiogenesis. The role of angiogenic factors in the pathogenesis of HIE is poorly understood, yet, angiogenin may be part of the molecular mechanisms underlying HIE. OBJECTIVE: Our objective was to explore the predictive value of angiogenin as a biochemical marker in early hypoxic ischemic encephalopathy staging. STUDY DESIGN: We prospectively studied 36 full term HIE neonates and 20 non- asphyxia neonates. Cord blood samples from all subjects immediately at delivery were withdrawn. Neurological examination and grading of HIE were performed during the first day of life. RESULTS: Concentrations of cord blood angiogenin were increased in infants with asphyxia when compared txht o controls (P = 0). Within the asphyxia group, the median cord blood angiogenin was significantly higher in stage III encephalopathy patient compared to stage I and stage II (p = 0). There was a negative correlation between pH, HCo3 level and angiogenin in stage II and stage III. CONCLUSION: Angiogenin helps in assessing the severity of HIE in neonates and is promising marker predicting the stage of hypoxia-ischemia so treatment may be initiated earlier.

QTL-based association analyses reveal novel genes influencing pleiotropy of metabolic syndrome (MetS).

OBJECTIVE: Metabolic Syndrome (MetS) is a phenotype cluster predisposing to type 2 diabetes and cardiovascular disease. We conducted a study to elucidate the genetic basis underlying linkage signals for multiple representative traits of MetS that we had previously identified at two significant QTLs on chromosomes 3q27 and 17p12. DESIGN AND METHODS: We performed QTL-specific genomic and transcriptomic analyses in 1,137 individuals from 85 extended families that contributed to the original linkage. We tested in SOLAR association of MetS phenotypes with QTL-specific haplotype-tagging SNPs as well as transcriptional profiles of peripheral blood mononuclear cells (PBMCs). RESULTS: SNPs significantly associated with MetS phenotypes under the prior hypothesis of linkage mapped to seven genes at 3q27 and seven at 17p12. Prioritization based on biologic relevance, SNP association, and expression analyses identified two genes: insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) at 3q27 and tumor necrosis factor receptor 13B (TNFRSF13B) at 17p12. Prioritized genes could influence cell-cell adhesion and adipocyte differentiation, insulin/glucose responsiveness, cytokine effectiveness, plasma lipid levels, and lipoprotein densities. CONCLUSIONS: Using an approach combining genomic, transcriptomic, and bioinformatic data we identified novel candidate genes for MetS.