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

Abstract

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.

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

“…SNP rs11066001 in the BRAP gene has been shown to be significantly associated with MI/CAD [8,9,11], carotid plaques [14] and Ankle-Brachial index (ABI) [12,13]. These associations imply that its genetic effect might be more evident in large artery atherosclerosis.…”

“…BRAP polymorphisms have been related to metabolic syndrome in a Chinese population [37], MI/CAD in Japanese, Korean and Taiwanese populations [9-11], and ABI and carotid atherosclerosis in a Taiwanese population [12-14]. Only one report showed that a BRAP polymorphism was associated with metabolic syndrome in European American and African American populations [38].…”

“…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].…”

The single nucleotide polymorphisms in BRAP decrease the risk of metabolic syndrome in a Chinese young adult population

“…12,13 The single nucleotide polymorphisms (SNPs) in BRAP were significantly associated with coronary artery disease in Asian populations. 12,14 Hsu et al 15 reported that the SNP (rs11066001) in BRAP has a synergistic effect with diabetes in the Chinese population.…”

Über den Einfluss einer verringerten BRAP-Expression auf die Entwicklung der Atherosklerose im ApoE-defizienten Mausmodell

“…Einteilung des Koronargefäßsystems in 15 Abschnitte und eine unterschiedliche Gewichtung der Läsion je nach Lokalisation)(Hsu et al 2011). Auch das Risiko für das Auftreten von atherosklerotischen Läsionen in der A. carotis ist bei Vorliegen des GG-Genotyps (SNP rs11066001, 270A>G) 1,58-fach erhöht.Liao et al fanden in dem Zusammenhang, dass BRAP durch Lipopolysaccharid, nicht aber durch artifiziell oxidiertes LDL in aortalen, glatten Muskelzellen induziert wird.…”