title: A SELDI-TOF-MS study in Lacunar Stroke with Subsequent Haptoglobin Phenotyping.
abstract: Using Surface-Enhanced Laser Desorption / Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS), we aimed to detect differences in protein profile in serum samples of two lacunar stroke subtypes. SELDI-TOF-MS, followed by protein identification, was performed in samples of 8 first-ever lacunar stroke patients with MR imaging showing a single symptomatic lacunar lesion (type 1), and 8 with multiple additional "silent" lacunar lesions and extensive white matter lesions (type 2). A 16 kDa protein, identified as alpha-2-chain of haptoglobin (Hp), was found to be overrepresented in type 1 compared to type 2 (peak intensity 12.5 vs. 5.0; p=0.02). As a polymorphism with two alleles, Hp-1 and Hp 2, determines the presence of alpha-1 and/or alpha-2-chains in the Hp-molecule, Hp phenotypic analysis was performed. Hp 1 : Hp-2 allele frequency was 0.562 : 0.438 in type 1 and 0.812 : 0.188 in type 2 (population reference approximately 0.4 : 0.6). We conclude that the overrepresentation of the alpha-2-chain in lacunar stroke type 1 compared to type 2 relates to a higher Hp-2 allele frequency in the former. Yet, compared to population reference, the phenotype distribution in both patient groups deviates towards a high Hp-1 allele frequency. Our findings suggest a role for the Hp gene in the etiology of cerebral small vessel disease. Larger studies are now needed to explore this new candidate gene.
authors.affiliation: Department of Neurology and Cardiovascular Research Institute Maastricht (CARIM), University Hospital Maastricht,The Netherlands. j.staals@neurologie.azm.nl
authors.forename: Julie
authors.initials: J
authors.lastname: Staals
authors.forename: Judith A P
authors.initials: JA
authors.lastname: Bons
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van Oostenbrugge
authors.forename: Iris L H
authors.initials: IL
authors.lastname: Knottnerus
authors.forename: Marja P
authors.initials: MP
authors.lastname: van Dieijen-Visser
authors.forename: Freek G
authors.initials: FG
authors.lastname: Bouwman
authors.forename: Edwin C
authors.initials: EC
authors.lastname: Mariman
authors.forename: Joris R
authors.initials: JR
authors.lastname: Delanghe
authors.forename: Jan
authors.initials: J
authors.lastname: Lodder
authors.forename: Will K W H
authors.initials: WK
authors.lastname: Wodzig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020520:Brain Infarction / Q000145:classification / Q000209:etiology* / Q000378:metabolism*; D005260:Female; D006242:Haptoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D020521:Stroke / Q000150:complications*
chemical_list: D006242:Haptoglobins