Haptoglobin genotype and its relation to asymptomatic cerebral small-vessel disease in type 1 diabetes.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9200299 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-5233 (Electronic) Linking ISSN: 09405429 NLM ISO Abbreviation: Acta Diabetol Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin : Springer International, c1991-

Stroke, Lacunar* ; Diabetes Mellitus, Type 1*/complications ; Diabetes Mellitus, Type 1*/epidemiology ; Diabetes Mellitus, Type 1*/genetics ; Cerebral Small Vessel Diseases*/epidemiology ; Cerebral Small Vessel Diseases*/genetics; Adult ; Humans ; Female ; Middle Aged ; Haptoglobins/genetics ; Cross-Sectional Studies ; Genotype ; Cerebral Hemorrhage/etiology ; Cerebral Hemorrhage/genetics ; Chromosomal Proteins, Non-Histone/genetics

Aim: Cerebral small-vessel disease (SVD) is prevalent in type 1 diabetes and has been associated with the haptoglobin variant allele Hp1. Contrarily, the Hp2-allele has been linked to cardiovascular disease and the role of haptoglobin-genotype in asymptomatic SVD is unknown. We, therefore, aimed to evaluate the alleles' association with SVD.
Methods: This cross-sectional study included 179 neurologically asymptomatic adults with type 1 diabetes (women 53%, mean age 39 ± 7 years, diabetes duration 23 ± 10 years, HbA 1c 8.1 ± 3.2% [65 ± 12 mmol/mol]). Examinations included genotyping (genotypes Hp1-1, Hp2-1, Hp2-2) by polymerase chain reaction, clinical investigation, and magnetic resonance brain images assessed for SVD manifestations (white matter hyperintensities, cerebral microbleeds, and lacunar infarcts).
Results: SVD prevalence was 34.6%. Haptoglobin genotype frequencies were 15.6% (Hp1-1), 43.6% (Hp1-2), and 40.8% (Hp2-2). Only diastolic blood pressure differed between the genotypes Hp1-1, Hp1-2, and Hp2-2 (81 [74-83], 75 [70-80], and 75 [72-81] mmHg, p = 0.019). Haptoglobin genotype frequencies by presence versus absence of SVD were 16.1%; 46.8%; 37.1% versus 15.4%; 41.9%; 42.7% (p = 0.758). Minor allele frequencies were 39.5% versus 36.3% (p = 0.553). Hp1 homozygotes and Hp2 carriers displayed equal proportions of SVD (35.7% vs 34.4%, p > 0.999) and SVD manifestations (white matter hyperintensities 14.3% vs 17.9%, p = 0.790; microbleeds 25.0% vs 21.9%, p = 0.904; lacunar infarcts 0% vs 3.6%, p > 0.999). Hp1-1 was not associated with SVD (OR 1.19, 95% CI 0.46-2.94, p = 0.712) when adjusting for age, blood pressure, and diabetic retinopathy.
Conclusions: Although the SVD prevalence was high, we detected no significant association between SVD and haptoglobin-genotype.
(© 2023. The Author(s).)

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275614 Academy of Finland; 316664 Academy of Finland; UAK10121MRI Academy of Finland; NNF OC0013659 Novo Nordisk Fonden

Keywords: Brain MRI; Cerebral small-vessel disease; Diabetes mellitus; Haptoglobin genotype; Stroke; Type 1 diabetes

0 (Haptoglobins)
0 (Chromosomal Proteins, Non-Histone)

Date Created: 20230301 Date Completed: 20230501 Latest Revision: 20230524

20240628

PMC10148779

10.1007/s00592-023-02059-2

36856861