A SELDI-TOF-MS Study in Lacunar Stroke with Subsequent Haptoglobin Phenotyping

Julie      Staals; Judith   A.P.   Bons; Robert   J.   van Oostenbrugge; Iris   L.H.   Knottnerus; Marja   P.   van Dieijen-Visser; Freek   G.   Bouwman; Edwin   C.   Mariman; Joris   R.   Delanghe; Jan      Lodder; Will   K.W.H.   Wodzig

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 ∼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.

Keywords: Lacunar infarcts, lacunar stroke, SELDI-TOF-MS, haptoglobin phenotypes

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