Genomic variant in CAV1 increases susceptibility to coronary artery disease and myocardial infarction

Abstract

Background The CAV1 gene encodes caveolin-1 expressed in cell types relevant to atherosclerosis. Cav-1-null mice showed a protective effect on atherosclerosis under the ApoE−/− background. However, it is unknown whether CAV1 is linked to CAD and MI in humans. In this study we analyzed a tagSNP for CAV1 in intron 2, rs3807989, for potential association with CAD. Methods and Results We performed case-control association studies in three independent Chinese Han populations from GeneID, including 1,249 CAD cases and 841 controls in Population I, 1,260 cases and 833 controls in Population II and 790 cases and 1,212 controls in Population III (a total of 3,299 cases and 2,886 controls). We identified significant association between rs3807989 and CAD in three independent populations and in the combined population (Padj=2.18×10−5, OR=1.19 for minor allele A). We also detected significant association between rs3807989 and MI (Padj=5.43×10−5, OR=1.23 for allele A). Allele A of SNP rs3807989 was also associated with a decreased level of LDL cholesterol. Although rs3807989 is a tagSNP for both CAV1 and nearby CAV2, allele A of SNP rs3807989 was associated with an increased expression level of CAV1 (both mRNA and protein), but not CAV2. Conclusions The data in this study demonstrated that rs3807989 at the CAV1/CAV2 locus was associated with significant risk of CAD and MI by increasing expression CAV1 (but not CAV2). Thus, CAV1 becomes a strong candidate susceptibility gene for CAD/MI in humans.

Role of Caveolin-1 in Diabetes and Its Complications

“…CAV1 SNP variants have been suggested to be linked to metabolic syndrome (MetS), a major risk factor for diabetes and coronary artery disease. Several CAV1 single-nucleotide polymorphisms (SNP) were found to associate with MetS: rs926198 in Caucasians and Hispanics [77], rs3807989 in the Chinese Han population [78], and rs1997623 in Kuwaiti children as shown by our previous study [79]. The forest plot in Figure 3 shows an association between LHDLC and MetS with the heterozygous genotype CA and the A-allele, meaning that a carrier of the A genotype has a higher chance of developing MetS in the studied population.…”

Association of eNOS and Cav-1 gene polymorphisms with susceptibility risk of large artery atherosclerotic stroke

“…The frequencies of observed alleles and genotypes for these polymorphisms were in Hardy-Weinberg proportions in the controls. On the basis of inferred phenotypic manifestations [10, 24–26], subjects who carried rare alleles of the eNOS 894T (coded for Aspartate), Cav-1 14713A , and 29107A were grouped together and considered a risk genotype in the following statistical analysis. For subjects who carried the homozygous eNOS GG genotype as a reference, a LAA stroke risk elevation was significant in carriers of combined GT/TT variant genotypes (OR = 1.72, 95% CI = 1.09–2.75).…”

“…Knockdown experiments of Cav-1 have been shown to cause cardiohypertrophy, diabetes, and pulmonary and focal cerebral ischemia and reperfusion injury [39–41]. Recent genome wide association reports have shown that Cav-1 SNPs are associated with stroke disease and that the Cav-1 G14713A elevates risk of coronary artery disease and myocardial infarction [24, 42–44]. However, some results are conflicting regarding the association between the Cav-1 polymorphisms and the risk of atrial fibrillation in cardiac arrhythmias [45].…”

KORONER KALP HASTALARINDA CAV1 rs3807990 VARYASYONUNUN LİPİD PROFİLİNDE DİYABETİK KOŞULLARA GÖRE FARKLI ETKİLERİ

“…Cav-1 proteininin plazma lipoprotein metabolizmasının düzenlenmesindeki rolü çok sayıda çalışmada gösteril-miştir (41,42). Ancak literatürde CAV1 gen varyasyonlarının kardiyovasküler hastalıklarla ilişkisini inceleyen sınırlı sayıda çalışma mevcuttur (27,29,30). Çalışmamızda incelediğimiz CAV1 rs3807989 polimorfizmi daha önceki çalışmalarda artmış atrial fibrilasyon riski ile ilişkili bulunmuştur (30).…”

“…CAV1 gen varyasyonlarıyla ilgili yapılmış sınırlı sayıda çalışma mevcuttur (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Literatürde CAV1 gen varyasyonlarının diyabetle ilişkilendirilmiş kardiyovasküler hastalıklarla ilişkisini inceleyen bir araştırma bulunmamaktadır.…”