Haptoglobin Hp1 Variant Does Not Associate with Small Vessel Disease

Lempiäinen, Juha; Ijäs, Petra; Niiranen, Teemu J.; Kaste, Markku; Karhunen, Pekka J.; Lindsberg, Perttu J.; Erkinjuntti, Timo; Melkas, Susanna

doi:10.3390/brainsci10010018

Cited by 3 publications

(3 citation statements)

References 27 publications

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“…Our results, however, agree with previous studies in individuals without diabetes, where no association between Hp-genotype and cerebral SVD were reported [ 23 , 30 ]. Nevertheless, findings have been contradictory also in individuals without diabetes and one previous study linked the genotype Hp1-1 to larger volumes of white matter hyperintensities [ 31 ].…”

Section: Discussionsupporting

confidence: 92%

“…Nevertheless, findings have been contradictory also in individuals without diabetes and one previous study linked the genotype Hp1-1 to larger volumes of white matter hyperintensities [ 31 ]. Reports on the association between Hp-genotype and lacunar infarctions are likewise contradictory [ 21 , 30 ], while, to the best of our knowledge, no studies on cerebral microbleeds exist.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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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, HbA1c 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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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“…Hb-HP was increased in the HDL of atherogenic/hyperlipidemic mice and in the HDL of individuals with CAD ( 29 ) and the amount of Hb bound to HDL correlates with the proinflammatory properties of dysfunctional HDL ( 29 ). Recently, a study reported that HP regulates vascular health through several means ( 30 ). Strikingly, we found that, compared to healthy participants, HP expression levels were significantly downregulated in stable CAD and ACS patients, which is inconsistent with the previous study; in animal models of myocardial ischemia, the HP protein has been implicated in coronary collateral development ( 31 ); Jahagirdar et al ( 25 ) found that HP protein levels were significantly upregulated in humans with cardiovascular disease, and HDL isolated from mice lacking this protein was involved in anti-inflammatory activity compared to Wild-type mice.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated circulating SOCS3 and HP expression associated with stable CAD and acute coronary syndrome: an integrated study based on bioinformatics analysis and case control validation

Zhang

et al. 2020

Anatol J Cardiol

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Objective: To extensively use blood transcriptome analysis to identify potential diagnostic and therapeutic targets for cardiovascular diseases. Methods: Two gene expression datasets (GSE59867 and GSE62646) were downloaded from GEO DataSets to identify altered blood transcriptomes in patients with ST-segment elevation myocardial infarction (STEMI) compared to stable coronary artery disease (CAD). Thereafter, several computational approaches were taken to determine functional roles and regulatory networks of differentially expressed genes (DEGs). Finally, the expression of dysregulated two hub genes–suppressor of cytokine signaling 3 (SOCS3) and haptoglobin (HP)–were validated in a case–control study. Results: A total of 119 DEGs were identified in the discovery phase, consisting of 71 downregulated genes and 48 upregulated genes; two hub modules consisting of two hub genes–SOCS3 and HP–were identified. In the validation phase, both SOCS3 and HP were significantly downregulated in the stable CAD and acute coronary syndrome (ACS) patients when compared with healthy controls. Meanwhile, HP was significantly upregulated in STEMI patients when compared with stable CAD patients (p=0.041). Logistic regression analysis indicated that: downregulated expression of HP correlated with increased risk of CAD [odds ratio (OR)=0.52, 95% confidence interval (CI)=0.31~0.87, p=0.013]; and downregulated expression of SOCS3 correlated with increased risk of ACS (OR=0.66, 95% CI=0.46~0.94, p=0.023) when age, gender, history of hyperlipidemia, diabetes and hypertension were included as covariates. Conclusion: Future clarification of how SOCS3 and HP influence the pathogenesis of disease may pave the way for the development of novel diagnostic and therapeutic methods.

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Haptoglobin Genotype Does Not Confer a Risk of Stroke in Type 1 Diabetes

et al. 2022

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The exon copy number variant in the haptoglobin gene is associated with cardiovascular and kidney disease. For stroke, previous research is inconclusive. We aimed to study the relationship between haptoglobin Hp1/2 genotype and stroke in individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study. We included two partially overlapping cohorts: one with haptoglobin genotypes determined using genotyping for 179 stroke cases and 517 matched controls, and the other using haptoglobin genotype imputation for a larger cohort of 500 stroke cases and 3,806 controls. We observed no difference in the Hp1-1, Hp2-1, and Hp2-2 genotype frequencies between the stroke cases and controls, neither in the genotyping nor the imputation cohorts. Haptoglobin genotypes were also not associated with the ischemic or hemorrhagic stroke subtypes. In our imputed haptoglobin cohort, 61% of individuals with stroke died during follow-up. However, the risk of death was not related to the haptoglobin genotype. Diabetic kidney disease and cardiovascular events were common in the cohort, but the haptoglobin genotypes were not associated with stroke when stratified by these complications. To conclude, the Hp1/2 genotypes did not affect the risk of stroke or survival after stroke in our type 1 diabetes cohort.

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Haptoglobin Hp1 Variant Does Not Associate with Small Vessel Disease

Cited by 3 publications

References 27 publications

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

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

Dysregulated circulating SOCS3 and HP expression associated with stable CAD and acute coronary syndrome: an integrated study based on bioinformatics analysis and case control validation

Haptoglobin Genotype Does Not Confer a Risk of Stroke in Type 1 Diabetes

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