Validation of eight genetic risk factors in East Asian populations replicated the association of BRAP with coronary artery disease

Hinohara, Kunihiko; Ohtani, Hideyuki; Nakajima, Toshiaki; Sasaoka, Taishi; Sawabe, Motoji; Lee, Bok-Soo; Ban, Jimin; Park, Jeong-Euy; Izumi, Tohru; Kimura, Akinori

doi:10.1038/jhg.2009.87

Cited by 15 publications

(14 citation statements)

References 25 publications

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“…The minor G allele of SNP rs11066001 was demonstrated to cause a higher BRAP expression level than the common A allele 2) . The findings were further replicated by an independent study using Japanese and Korean populations 3) . In addition, our group showed an association between SNP rs11066001 and carotid atherosclerosis (unpublished data) and coronary stenosis (unpublished data).…”

supporting

confidence: 68%

Polymorphism of 270 A > G in BRAP is Associated with Lower Ankle-Brachial Index in a Taiwanese Population

Tsai

Lin

Hsu

et al. 2011

JAT

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Aims:The single nucleotide polymorphism (SNP) rs11066001 of BRAP has been shown to be associated with myocardial infarction (MI), coronary atherosclerosis and carotid atherosclerosis, but it is not clear whether it also plays a role in peripheral artery disease (PAD). The ankle-brachial index (ABI) is often used as a non-invasive measure of PAD; therefore, the aim of this study was to test for a relationship between the SNP rs11066001 and ABI. Methods: A total of 537 high-risk subjects with a family history of MI or stroke completed a health survey, including a physical examination, blood test and measurement of ABI. Among them, 523 subjects had the genotypes. Association analyses between the genotype of BRAP and ABI were performed by multiple linear and logistic regressions with adjustment for covariates. Results: We found that the GG genotype is significantly associated with a lower ABI value. For the lowest ABI tertile, the GG genotype had an OR of 2.87 (p 0.018) when compared with the middle ABI tertile, and OR of 2.92 (p 0.015) when compared to the highest ABI tertile. Women with the GG genotype had a lower ABI value than men with the same genotype (p 0.012). Accordingly, women carrying this GG risk genotype may have a higher risk for PAD. Conclusion: Our findings provide additional evidence that support the genetic effect of BRAP on diverse cardiovascular phenotypes. J Atheroscler Thromb, 2011; 18:413-420.

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supporting

confidence: 68%

Polymorphism of 270 A > G in BRAP is Associated with Lower Ankle-Brachial Index in a Taiwanese Population

Tsai

Lin

Hsu

et al. 2011

JAT

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“…Several large-scale association studies including GWAS studies have identified several loci associated with the risk of CAD and MI [2,3,5,6,7,9,10,14,15,16,17,18,19,20]. However, not all of the identified associations could be replicated in other studies.…”

Section: Discussionmentioning

confidence: 62%

“…However, not all of the identified associations could be replicated in other studies. Kunihiko et al [20] validated 8 genetic risk factors in East-Asian populations (Japanese and Korean, a case-control study with a total of 1,480 CAD cases and 2,115 controls) and only one SNP in BRAP (rs11066001) showed a significant association with CAD. Failure to replicate the association with other SNPs reported in European populations might suggest that their contributions to CAD were not large enough in European populations.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect between BRAP Polymorphism and Diabetes on the Extent of Coronary Atherosclerosis in the Chinese Population

Hsu

Lin²,

Su³

et al. 2011

Cardiology

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Objectives: Coronary artery disease (CAD) is a multifactorial disease and influenced by genetics. We previously reported that a single nucleotide polymorphism (rs11066001) in the BRAP gene was related to the risk of myocardial infarction. However, it is unclear whether rs11066001 is associated with the extent of coronary atherosclerosis. Methods: We enrolled 732 patients scheduled for diagnostic coronary angiography. Angiographic presence of significant CAD (0 or 1), clinical vessel score (CVS, 0–3 vessels) and diffuse score (DS, 0–11.5) were used to evaluate the extent of coronary atherosclerosis. Genotyping was carried out by the TaqMan technology. Results: Of all patients, 558 (76.2%) had significant CAD. The odds ratio for the GG to the AA genotype was 2.45 (95% CI 1.13–5.34, p = 0.024) for the presence of significant CAD. The CVS was correlated with the frequency of genotypes in the recessive model (p = 0.001). Regression analysis showed a significant association between rs11066001 and the presence of significant CAD and DS (all p < 0.05). There was a synergistic effect between rs11066001 and diabetes on the occurrence of significant CAD (p < 0.001 for interaction). Conclusion: The BRAP rs11066001 gene is associated with the extent of coronary atherosclerosis and has a synergistic effect with diabetes on the occurrence of significant CAD in the Chinese population.

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“…Of note is that rs11066001 is in LD with rs3782886, with R 2 of 0.891 and D` of 1 in our data. 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].…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Liu

et al. 2014

PLoS ONE

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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.

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Validation of eight genetic risk factors in East Asian populations replicated the association of BRAP with coronary artery disease

Cited by 15 publications

References 25 publications

Polymorphism of 270 A > G in BRAP is Associated with Lower Ankle-Brachial Index in a Taiwanese Population

Polymorphism of 270 A > G in BRAP is Associated with Lower Ankle-Brachial Index in a Taiwanese Population

Synergistic Effect between BRAP Polymorphism and Diabetes on the Extent of Coronary Atherosclerosis in the Chinese Population

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

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