Lack of association between a functional variant of the BRCA-1 related associated protein (BRAP) gene and ischemic stroke

Liao, Yi‐Chu; Lin, Hsiu-Fen; Guo, Yuh‐Cherng; Chen, Chung-Hung; Huang, Zhi-Zhang; Juo, Suh‐Hang Hank; Lin, Ruey‐Tay

doi:10.1186/1471-2350-14-17

Cited by 13 publications

(8 citation statements)

References 37 publications

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“…In fact, reduced capability for endothelial repair [23, 30] and hypertension [2] characteristic of short stature might perform an important role in the incidence of stroke for participants with short stature. Since BRAP is reportedly associated with atherosclerosis [15] but not associated with stroke [16] and SNPs (rs3782886) are associated with short stature [14], SNP (rs3782886) might perform an import function for the prevention of stroke for participants with short stature by stimulating endothelial repair. In the present study, even though SNP (rs3782886) was found to be associated with a high platelet count, which is related to hypertension, no significant association between SNP (rs3782886) and hypertension was observed, which partly supports the aforementioned mechanisms because adequate endothelial maintenance was performed predominantly for normal body weight participants.…”

Section: Discussionmentioning

confidence: 99%

“…Single-nucleotide polymorphism (SNP) (rs3782886) in breast cancer suppressor BRCA1-related associated protein (BRAP) is reportedly associated with risk of myocardial infarction [13], while SNP (rs3782886) is also found to be associated with short stature in a previous study by us [14]. Another study reported that BRAP activates inflammatory cascades and increases the risk of carotid atherosclerosis [15] but is not associated with risk of stroke [16]. Although an SNP (rs3782886) could be associated with carotid atherosclerosis, these studies indicate that it might also have a beneficial effect on stroke prevention by inducing endothelial repair in participants with short stature; otherwise, these participants would have high risks of hypertension [2], carotid atherosclerosis [3], and stroke [4].…”

Section: Introductionmentioning

confidence: 99%

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Short stature-related single-nucleotide polymorphism (SNP) activates endothelial repair activity in elderly Japanese

Shimizu

Yamanashi

Noguchi

et al. 2019

Environ Health Prev Med

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Background Hypertension and atherosclerosis are bidirectionally related, while platelet count could serve as an indicator of endothelial repair. Therefore, high platelet counts could be associated with hypertension by indicating more intense endothelial repair activity. Furthermore, short stature has been shown to constitute a risk of atherosclerosis. Since inflammation-related single-nucleotide polymorphism (SNP (rs3782886)) is reportedly associated with myocardial infarction and short stature, rs3782886 could be associated with a high platelet count and thus more intense endothelial repair activity. Methods We conducted a cross-sectional study of 988 elderly Japanese who participated in a general health check-up. Short stature was defined as a height of at or under the 25th percentile of the study population, and high platelet count as the highest tertiles of the platelet levels. Results High platelet counts were found to be independently and positively associated with hypertension while rs3782886 was independently associated with high platelet levels and short stature. The classical cardiovascular risk factor-adjusted odds ratio (OR) and 95% confidence interval (CI) of high platelet count for hypertension was 1.34 (1.02, 1.77). With non-minor homo of the rs3782886 as the reference group, the adjusted OR and 95% CI for high platelet count and short stature of minor home were 2.40 (1.30, 4.42) and 2.21 (1.16, 4.21), respectively. Conclusion SNP (rs3782886) was shown to be associated with high platelet count and short stature. This result partly explains how a genetic factor can influence the impact of height on endothelial repair.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Short stature-related single-nucleotide polymorphism (SNP) activates endothelial repair activity in elderly Japanese

Shimizu

Yamanashi

Noguchi

et al. 2019

Environ Health Prev Med

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“…Recently, identification of dysregulated pathways was proposed as possible biomarkers for such disorders [43, 44]. This study conferred a strong evidence of similarities on the pathogenesis between insulin resistance and atherosclerosis, which could support diagnostic processes and drug design in a more effective manner facilitating a more personalized medicine in patients with metabolic syndrome.…”

Section: Discussionmentioning

confidence: 90%

Common dysregulated pathways in obese adipose tissue and atherosclerosis

Moreno-Viedma

Amor

Sarabi

et al. 2016

Cardiovasc Diabetol

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BackgroundThe metabolic syndrome is becoming increasingly prevalent in the general population that is at simultaneous risk for both type 2 diabetes and cardiovascular disease. The critical pathogenic mechanisms underlying these diseases are obesity-driven insulin resistance and atherosclerosis, respectively. To obtain a better understanding of molecular mechanisms involved in pathogenesis of the metabolic syndrome as a basis for future treatment strategies, studies considering both inherent risks, namely metabolic and cardiovascular, are needed. Hence, the aim of this study was to identify pathways commonly dysregulated in obese adipose tissue and atherosclerotic plaques.MethodsWe carried out a gene set enrichment analysis utilizing data from two microarray experiments with obese white adipose tissue and atherosclerotic aortae as well as respective controls using a combined insulin resistance-atherosclerosis mouse model.ResultsWe identified 22 dysregulated pathways common to both tissues with p values below 0.05, and selected inflammatory response and oxidative phosphorylation pathways from the Hallmark gene set to conduct a deeper evaluation at the single gene level. This analysis provided evidence of a vast overlap in gene expression alterations in obese adipose tissue and atherosclerosis with Il7r, C3ar1, Tlr1, Rgs1 and Semad4d being the highest ranked genes for the inflammatory response pathway and Maob, Bckdha, Aldh6a1, Echs1 and Cox8a for the oxidative phosphorylation pathway.ConclusionsIn conclusion, this study provides extensive evidence for common pathogenic pathways underlying obesity-driven insulin resistance and atherogenesis which could provide a basis for the development of novel strategies to simultaneously prevent type 2 diabetes and cardiovascular disease in patients with metabolic syndrome.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0441-2) contains supplementary material, which is available to authorized users.

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“…Japanese individuals are characterized by higher rates of stroke than myocardial infarction 27 . Even SNPs in BRAP have been reported to be associated with the risk of myocardial infarction 2 , but not with stroke 28 . As such, genetic factor has the potential to have a strong beneficial influence on preventing hypertension, especially in the Japanese population, which has a higher risk of stroke.…”

Section: Discussionmentioning

confidence: 99%

Potential mechanisms underlying the association between single nucleotide polymorphism (BRAP and ALDH2) and hypertension among elderly Japanese population

Shimizu

Arima

Noguchi

et al. 2020

Sci Rep

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Minor allele frequency (MAF) of rs3782886 (BRAP) and rs671 (ALDH2) are reported to be inversely associated with blood pressure. Another study revealed that hematopoietic activity which is evaluated by reticulocytes could influenced on hypertension status partly by indicating activity of endothelial maintenance. Therefore, to evaluate the association between genetic factor and hypertension, influence of hematopoietic activity should be considered. A multi-faced analysis was performed in a simple general elderly population model (1,313 older Japanese aged 60-98 years). Participants were stratified by median values of reticulocytes (5.21 × 10 4 cells/μL for men and 4.65 × 10 4 cells/ μL for women). Independent of known cardiovascular risk factors, MAF of rs3782886 and rs671 are significantly inversely associated with hypertension for participants with high hematopoietic activity (high reticulocytes level) (fully adjusted odds ratio (ORs) were 0.72 (0.55, 0.96) for rs3782886 and 0.72 (0.54, 0.96) for rs671) but not for low reticulocytes count (the corresponding values were 1.05 (0.79, 1.39) and 1.08 (0.81, 1.45), respectively). Hematopoietic activity evaluated by reticulocytes levels could influence on the association between single nucleotide polymorphism (rs3782886 and rs671) and hypertension. Those results were efficient tool to clarify the part of the mechanism that underlying the association between genetic factor and hypertension. Atherosclerosis is generally considered to be positively associated with hypertension 1. A single nucleotide polymorphism (SNP) (rs3782886) in breast cancer suppressor BRCA1-related associated protein (BRAP) has been associated with the risk of developing myocardial infarction 2. Another study reported that BRAP activates inflammatory cascades, increasing the risk of carotid atherosclerosis 3. Even though the minor allele frequency (MAF) of rs3782886, and aldehyde dehydrogenase 2 (ALH2) polymorphism rs671 are significantly inversely associated with both systolic and diastolic blood pressure 4. Since strong linkage disequilibrium (LD) values between rs3782886 and rs671 have been reported 5 , rs671 could have same the characteristics of rs3782886. However, the mechanism underlying the association between hypertension and these genetic factors (rs3782886 and rs671) have not yet been elucidated. Atherosclerosis is involved in aggressive endothelial repair. Therefore, the favorable association of genetics factor (rs3782886 and rs671) with hypertension may be caused by stimulating endothelial repair.

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Lack of association between a functional variant of the BRCA-1 related associated protein (BRAP) gene and ischemic stroke

Cited by 13 publications

References 37 publications

Short stature-related single-nucleotide polymorphism (SNP) activates endothelial repair activity in elderly Japanese

Short stature-related single-nucleotide polymorphism (SNP) activates endothelial repair activity in elderly Japanese

Common dysregulated pathways in obese adipose tissue and atherosclerosis

Potential mechanisms underlying the association between single nucleotide polymorphism (BRAP and ALDH2) and hypertension among elderly Japanese population

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