Abstract
Haptoglobin (Hp) is a plasma protein that binds free hemoglobin and protects tissues from oxidative damage. An Hp2 allele has been associated with an increased risk of cardiovascular complications. On the other hand, recent studies have suggested that Hp1 allele increases risk to develop severe cerebral small vessel disease. We aimed to replicate this finding in a first-ever stroke patient cohort. Hp was genotyped by PCR and gel electrophoresis in the Helsinki Stroke Aging Memory Study in patients with DNA and magnetic resonance imaging (MRI) available (SAM; n = 316). Lacunar infarcts and white matter lesions (WML) classified by Fazekas grading from brain MRI were associated with Hp genotypes. As population controls, we used participants of Cardiovascular diseases—a sub study of Health 2000 Survey (n = 1417). In the SAM cohort, 63.0% of Hp1-1 carriers (n = 46), 52.5% of Hp1-2 carriers (n = 141) and 51.2% of Hp2-2 carriers (n = 129) had severe WML (p = 0.372). There was no difference in severe WMLs between Hp1-1 vs. Hp1-2 and Hp2-2 carriers (p = 0.201). In addition, 68.9% of Hp1-1 carriers (n = 45), 58.5% of Hp1-2 carriers (n = 135), and 61.8% of Hp2-2 carriers (n = 126) had one or more lacunar lesions (p = 0.472). There was no difference in the number of patients with at least one lacunar infarct between Hp1-1 vs. Hp1-2 and Hp2-2 groups (p = 0.322). Neither was there any difference when diabetic patients (type I and II) were examined separately. Hp1 allele is not associated with an increased risk for cerebral small vessel disease in a well-characterized Finnish stroke patient cohort.
Highlights
Haptoglobin (Hp) is a plasma protein that binds free hemoglobin (Hb)
Hp1 allele is not associated with an increased risk for cerebral small vessel disease in a well-characterized Finnish stroke patient cohort
Hp2-2 binds with high affinity to apolipoprotein 1A (APO1A) and apolipoprotein E (APOE) in high density
Summary
Haptoglobin (Hp) is a plasma protein that binds free hemoglobin (Hb). This protects tissues from heme-iron induced oxidative damage and Hb-associated nitric oxide (NO) scavenging [1,2,3].Hp regulates vascular health by several means [4,5,6,7,8,9,10].The Hp gene exists in two major variant alleles, Hp1 and Hp2, giving rise to three protein isoforms (Hp1-1, Hp1-2 and Hp2-2). Haptoglobin (Hp) is a plasma protein that binds free hemoglobin (Hb). This protects tissues from heme-iron induced oxidative damage and Hb-associated nitric oxide (NO) scavenging [1,2,3]. Hp regulates vascular health by several means [4,5,6,7,8,9,10]. The Hp gene exists in two major variant alleles, Hp1 and Hp2, giving rise to three protein isoforms (Hp1-1, Hp1-2 and Hp2-2). Hp1-1 has good heme-recycling and antioxidant properties [1]. Hp2 allele recycles heme less efficiently and has poorer antioxidant properties [1]. Hp2-2 binds with high affinity to apolipoprotein 1A (APO1A) and apolipoprotein E (APOE) in high density
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