Haptoglobin Polymorphism and Lacunar Stroke

Abstract

Haptoglobin (Hp) 2-2 phenotype has been associated with peripheral and coronary artery disease and risk of vascular complications in diabetic patients, but any association of Hp polymorphism with cerebrovascular disease has not been explored so far. We aimed to study Hp polymorphism in a sample of 124 patients with a rather homogeneous type of cerebrovascular disease, namely first symptomatic lacunar stroke due to small vessel disease, in comparison with a large (n=918) control group. Hp phenotypes were determined using starch gel electrophoresis. Hp1 allele frequency was significantly higher in patients than in controls (0.480 vs. 0.395, p<0.05), mainly due to a lower Hp2-2 phenotype frequency (25.0 vs. 36.3 %; OR 0.59; 95%CI 0.38-0.90; p<0.05). This was even more pronounced in younger (<or=60 years) patients (Hp1 allele frequency 0.539). Concomitant asymptomatic lacunar lesions were present in 82 patients, extensive white matter lesions in 47 patients. The association between Hp1 and lacunar stroke suggests that Hp may serve different functions depending on the pathological processes in various types of vascular disease in different organs. The association between Hp1 and lacunar stroke may relate to blood-brain barrier dysfunction, to the association between hypertension and cerebral small vessel disease, or a special dependence of small vessel wall integrity on Hp2-2 related angiogenic potential. The presence of concomitant signs of cerebral small vessel disease weakened the association between Hp1 and lacunar stroke, which could reflect a difference in underlying vascular pathophysiology in which Hp phenotype may play a different role.

Haptoglobin genotype and cerebrovascular disease incidence in type 1 diabetes

“…Taken together, these findings suggest an adverse effect of vitamin E therapy in carriers of the Hp 1 allele, which could be due to exacerbation of a potential stroke susceptibility in the Hp 1-1 group, should findings in the general population (5-7) hold true also in diabetes. To our knowledge, however, such assessments in diabetes have yet to be conducted.…”

“…Specifically, compared to healthy volunteers, a greater frequency of the Hp 1 allele was found among patients with a first symptomatic small vessel lacunar stroke and Hp 1 was also related to white matter lesions (5). Similarly to our findings, the direct effect of the Hp 1 allele appeared more pronounced among those with hypertension, while an association was absent in normotensive individuals.…”

“…Recently, studies in the general population showed a lower prevalence of the Haptoglobin (Hp) 2 allele among individuals with cerebrovascular disease (5-7), a surprising observation given consistent prospective findings of an increased cardiovascular and end-stage renal disease (8) risk associated with the Hp 2 allele in diabetes.…”

The clinical manifestations and pathophysiology of cerebral small vessel disease

“…Chronic ischemia in frontal white matter could interrupt frontal-cerebellar circuits, induce hypometabolism in cerebellar regions, and decrease perfusion and apparent diffusion coefficient (ADC) [43] . for MTHFR C677T, ApoE/epsilon4 or PAI-A 4G/5G polymorphism [44] . Analysis of haptoglobin (Hp) 2-2 phenotype in a group of patients with first symptomatic lacunar stroke has revealed that Hp1 allele frequency is significantly higher than that in control group, mainly due to a lower Hp2-2 phenotype frequency.…”

Blood biomarkers to identify ischemic stroke etiologies

“…Hp Gene P00737 Hp1-1 phenotype has been associated with SVD stroke patients in the chronic stage (124 patients included in the study) [75] Hcy Amino acid Involved in vascular damage. High levels of Hcy associated with SVD stroke in different population studies including all etiologies.…”