BRAP Activates Inflammatory Cascades and Increases the Risk for Carotid Atherosclerosis

Liao, Yi‐Chu; Wang, Yung Song; Guo, Yuh Cherng; Ozaki, Kouichi; Tanaka, Toshihiro; Lin, Hsiu-Fen; Chang, Ming Hong; Chen, Ku Chung; Yu, Ming; Sheu, Sheng Hsiung; Juo, Suh Hang Hank

doi:10.2119/molmed.2011.00043

Cited by 38 publications

(58 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some studies reported that two SNPs—rs11066001 and rs3782886—in BRAP were significantly associated with coronary artery disease in Asian populations [14], [35], and metabolic syndrome in the Han Chinese population [36]. Another study reported the association of rs11066001 with carotid atherosclerosis in Taiwanese [15]. Notably, all these studies were conducted in Asian populations.…”

Section: Discussionmentioning

confidence: 99%

A Two-Stage Association Study Suggests BRAP as a Susceptibility Gene for Schizophrenia

Zhang

Liu

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Schizophrenia (SZ) is a neurodevelopmental disorder in which altered immune function typically plays an important role in mediating the effect of environmental insults and regulation of inflammation. The breast cancer suppressor protein associated protein (BRAP) is suggested to exert vital effects in neurodevelopment by modulating the mitogen-activated protein kinase cascade and inflammation signaling. To explore the possible role of BRAP in SZ, we conducted a two-stage study to examine the association of BRAP polymorphisms with SZ in the Han Chinese population. In stage one, we screened SNPs in BRAP from our GWAS data, which detected three associated SNPs, with rs3782886 being the most significant one (P = 2.31E-6, OR = 0.67). In stage two, we validated these three SNPs in an independently collected population including 1957 patients and 1509 controls, supporting the association of rs3782886 with SZ (P = 1.43E-6, OR = 0.73). Furthermore, cis-eQTL analysis indicates that rs3782886 genotypes are associated with mRNA levels of aldehyde dehydrogenase 2 family (ALDH2) (P = 0.0039) and myosin regulatory light chain 2 (MYL2) (P < 1.0E-4). Our data suggest that the BRAP gene may confer vulnerability for SZ in Han Chinese population, adding further evidence for the involvement of developmental and/or neuroinflammatory cascades in the illness.

show abstract

Section: Discussionmentioning

confidence: 99%

A Two-Stage Association Study Suggests BRAP as a Susceptibility Gene for Schizophrenia

Zhang

Liu

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Furthermore, we found that the BRAP protein interacts several molecules related to inflammation and cell proliferation, such as major components of I kappa kinase (IKK)-signalosome ( Figure 1). 51 Taken together, these results implicated that a higher BRAP expression level from risk allele may enhance the degree of inflammation through activation of NFκB-I kappa kinase (IKK)-signalosome proteins, thereby playing a critical role in the pathogenesis of MI. In Figure 1, we show possible implication of BRAP cascade and inflammatory molecules in the pathogenesis of MI.…”

Section: Brap Encoding a Galectin-2-binding Protein And MImentioning

confidence: 92%

Molecular genetics of coronary artery disease

Ozaki

Tanaka

2015

J Hum Genet

Self Cite

View full text Add to dashboard Cite

Coronary artery disease (CAD) including myocardial infarction (MI) is a common disease and among the leading cause of death in the world. The onset of CAD depends on complex interactions of environmental and genetic factors. To clarify the genetic architecture of MI, we started a genome-wide association study (GWAS) using nearly 100 000 gene-based single-nucleotide polymorphisms (SNPs) from 2000, and identified LTA associated with the increased risk of MI in Japanese population. To our knowledge, this is the first study identified a genetic factor for common disease by GWAS in the worldwide. Through examining the LTA cascade by combination of molecular biological and genetic analyses, we have identified additional MI susceptible genes, LGALS2, PSMA6 and BRAP, so far. Nowadays a lot of large-scale GWAS have identified numerous genetic risk factors for common diseases. In CAD, 51 loci with GWAS significance (P<5 × 10(-8)) have collectively identified by recent large-scale GWAS mainly in Caucasian descent. In this review, we discuss recent advances in molecular genetics for CAD.

show abstract

“…The rare GG homozygote of the single nucleotide polymorphism (SNP) rs11066001 in the BRAP gene was found to be associated with a 1.31- to 1.47-fold risk for MI in Chinese and Japanese populations [8]. SNP rs11066001 has also been shown to be related to coronary artery disease (CAD) [9-11], ankle-brachial index [12,13] and carotid atherosclerosis [14]. In vitro studies showed that the G allele of SNP rs11066001 had an elevated BRAP expression, which exaggerated the activity of nuclear factor-kappa B (NF-κB) [8].…”

Section: Introductionmentioning

confidence: 99%

“…NF-κB is considered to be the “master regulator” of inflammatory cascades. Our recent study demonstrated that BRAP could enhance NF-κB nuclear translocation and subsequently initiated the transcription of inflammatory cytokines [14]. Because atherosclerosis can be caused by a chronic inflammatory condition, BRAP might play a role in the occurrence of ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

“…The aim of the present study was to investigate whether BRAP confers a risk for stroke in a Taiwanese population. Polymorphism rs11066001 was selected because it is a functional locus that affects the transcription of BRAP [14], and rs11066001 has also been shown to have the strongest association with MI risk [8]. We performed subgroup analysis by stroke subtype and by stroke onset age.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2013

Self Cite

View full text Add to dashboard Cite

BackgroundAtherosclerosis shares common pathogenic features with myocardial infarction (MI) and ischemic stroke. BRCA-1 associated protein (BRAP), a newly identified risk gene for MI, aggravates the inflammatory response in atherosclerosis. The aim of this study was to test the association between the BRAP gene and stroke in a Taiwanese population.MethodsA total of 1,074 stroke patients and 1,936 controls were genotyped for the functional SNP rs11066001. In our previous studies, the rare allele of this SNP has been repeatedly shown to exert a recessive effect. Therefore, in the current study, we tested for the same recessive model. First, the genotype distributions between all the controls and all the stroke cases were compared. Then to reduce heterogeneity, we explored several population subsets by selecting young stroke subjects (using 45 years of age as the cutoff point), age- and sex-comparable controls, plaque-free controls, and stroke subtypes.ResultsWe did not find any significant association for the entire data set (OR = 0.94, p = 0.74) or for the subset analyses using age- and sex-comparable controls (p = 0.70) and plaque-free controls (p = 0.91). Analyses of the four stroke subtypes also failed to show any significant associations (p = 0.42 – 0.98). For both young and old subjects, the GG genotype of rs11066001 was similar in the stroke cases and unmatched controls (8.1% vs. 9.4% in young subjects and 8.0% vs. 7.8% in old subjects). Comparing stroke cases with plaque-free controls also failed to find any significant association.ConclusionsThe BRAP polymorphism may not play an important role in ischemic stroke in the studied population.

show abstract

BRAP Activates Inflammatory Cascades and Increases the Risk for Carotid Atherosclerosis

Cited by 38 publications

References 33 publications

A Two-Stage Association Study Suggests BRAP as a Susceptibility Gene for Schizophrenia

A Two-Stage Association Study Suggests BRAP as a Susceptibility Gene for Schizophrenia

Molecular genetics of coronary artery disease

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

Contact Info

Product

Resources

About