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Articles by A. H Kissebah
Total Records ( 2 ) for A. H Kissebah
  L. A Collins , S. P Mirza , A. H Kissebah and M. Olivier

The implication of the various lipoprotein classes in the development of atherosclerotic cardiovascular disease has served to focus a great deal of attention on these particles over the past half-century. Using knowledge gained by the sequencing of the human genome, recent research efforts have been directed toward the elucidation of the proteomes of several lipoprotein subclasses. One of the challenges of such proteomic experimentation is the ability to initially isolate plasma lipoproteins subsequent to their analysis by mass spectrometry. Although several methods for the isolation of plasma lipoproteins are available, the most commonly utilized techniques require large sample volumes and may cause destruction and dissociation of lipoprotein particle-associated proteins. Fast protein liquid chromatography (FPLC) is a nondenaturing technique that has been validated for the isolation of plasma lipoproteins from relatively small sample volumes. In this study, we present the use of FPLC in conjunction with nano-HPLC-ESI-tandem mass spectrometry as a new integrated methodology suitable for the proteomic analysis of human lipoprotein fractions. Results from our analysis show that only 200 µl of human plasma suffices for the isolation of whole high density lipoprotein (HDL) and the identification of the majority of all known HDL-associated proteins using mass spectrometry of the resulting fractions.

  Y Zhang , E. M Smith , T. M Baye , J. V Eckert , L. J Abraham , E. K Moses , A. H Kissebah , L. J Martin and M. Olivier

Neurotransmitters such as serotonin (5-hydroxytryptamine, 5-HT) work closely with leptin and insulin to fine-tune the metabolic and neuroendocrine responses to dietary intake. Losing the sensitivity to excess food intake can lead to obesity, diabetes, and a multitude of behavioral disorders. It is largely unclear how different serotonin receptor subtypes respond to and integrate metabolic signals and which genetic variations in these receptor genes lead to individual differences in susceptibility to metabolic disorders. In an obese cohort of families of Northern European descent (n = 2,209), the serotonin type 5A receptor gene, HTR5A, was identified as a prominent factor affecting plasma levels of triglycerides (TG), supported by our data from both genome-wide linkage and targeted association analyses using 28 publicly available and 12 newly discovered single nucleotide polymorphisms (SNPs), of which 3 were strongly associated with plasma TG levels (P < 0.00125). Bayesian quantitative trait nucleotide (BQTN) analysis identified a putative causal promoter SNP (rs3734967) with substantial posterior probability (P = 0.59). Functional analysis of rs3734967 by electrophoretic mobility shift assay (EMSA) showed distinct binding patterns of the two alleles of this SNP with nuclear proteins from glioma cell lines. In conclusion, sequence variants in HTR5A are strongly associated with high plasma levels of TG in a Northern European population, suggesting a novel role of the serotonin receptor system in humans. This suggests a potential brain-specific regulation of plasma TG levels, possibly by alteration of the expression of HTR5A.

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