Variants in ANRIL gene correlated with its expression contribute to myocardial infarction risk.

ANRIL (antisense non-coding RNA in the INK4 locus), located at the 9p21.3 locus, has been known to be closely associated with the risk of coronary artery disease (CAD). To date, studies of the 9p21.3 variants on CAD risk mainly focus on the non-coding region of ANRIL. However, the biological significance of the variants on ANRIL promoter and exons is still unknown. Here we investigate whether the variants on ANRIL promoter and exons have an effect on myocardial infarction (MI) risk, and further analyze the association of these variants with the expression of ANRIL transcript. We did not find any common variants with minor allele frequencies (MAF) larger than 5% in ANRIL promoter by sequencing 1.6kb upstream of the start codon. Unconditional logistic regression analysis revealed that two SNPs in ANRIL exons, rs10965215 and rs10738605, were significantly associated with MI risk. Further studies revealed that ANRIL transcript EU741058.1 expression levels of rs10965215 and rs10738605 risk genotypes were borderline lower than those of protective genotypes. Our data provide the evidence that the variants rs10965215 and rs10738605 in ANRIL exons contribute to MI risk in the Chinese Han population which might be correlated with the expression of its transcript EU741058.1.

Association of lincRNA-p21 Haplotype with Coronary Artery Disease in a Chinese Han Population.

lincRNA-p21 plays an important role in the pathogenesis and progression of coronary artery disease (CAD). To date, the biological significance of polymorphisms in lincRNA-p21 on CAD risk remains unknown. Here we aimed to evaluate the influence of lincRNA-p21 polymorphisms on individual susceptibility to CAD. Genotyping of four tagSNPs (rs9380586, rs4713998, rs6930083, and rs6931097) within lincRNA-p21 gene was performed in 615 CAD and 655 controls. The haplotype analysis showed that the haplotype G-A-A-G (rs9380586-rs4713998-rs6930083-rs6931097) was statistically significantly associated with the reduced risk for CAD (OR = 0.78, P = 0.023). Stratified analysis revealed that G-A-A-G haplotype was at a significantly lower risk for myocardial infarction (MI) (OR = 0.68, P = 0.010). We also found that haplotype G-A-A-G had a more pronounced decreased risk for premature CAD or MI subjects (OR = 0.67, P = 0.017 for premature CAD, and OR = 0.65, P = 0.041 for premature MI, resp.). Our data provide the first evidence that the G-A-A-G haplotype of lincRNA-p21 is associated with decreased risk of CAD and MI, particularly among premature CAD/MI in the Chinese Han population. Further studies with more subjects and in diverse ethnic populations are warranted to clarify the general validity of our findings.

Two tagSNPs rs352493 and rs3760908 within SIRT6 Gene Are Associated with the Severity of Coronary Artery Disease in a Chinese Han Population.

SIRT6 has been demonstrated to exert protective effects on endothelial cells and is closely associated with lipid metabolism, glucose metabolism, and obesity, indicating an important role in the pathogenesis and progression of coronary artery disease (CAD). Nonetheless, the biological significance of SIRT6 variants on CAD is far to be elucidated. Here we aimed to investigate the influence of SIRT6 polymorphisms on individual susceptibility and severity of CAD. Multivariate logistic regression analysis exhibited no significant association between these five polymorphisms and CAD risk in the genotype and allele frequencies. However, we found that the rs352493 polymorphism in SIRT6 exhibited a significant effect on the severity of CAD; C allele (χ(2) = 7.793, adjusted P = 0.013) and the combined CC/CT genotypes (χ(2) = 5.609, adjusted P = 0.031) presented the greater CAD severity. In addition, A allele (χ(2) = 5.208, adjusted P = 0.046) and AA (χ(2) = 4.842, adjusted P = 0.054) of rs3760908 were also associated with greater CAD severity in Chinese subjects. Our data provided the first evidence that SIRT6 tagSNPs rs352493 and rs3760908 play significant roles in the severity of CAD in Chinese Han subjects, which might be useful predictors of the severity of CAD.

LincRNA-p21: Implications in Human Diseases.

Long noncoding RNAs (lncRNAs), which lack significant protein-coding capacity, regulate various biological processes through diverse and as yet poorly understood molecular mechanisms. However, a number of studies in the past few years have documented important functions for lncRNAs in human diseases. Among these lncRNAs, lincRNA-p21 has been proposed to be a novel regulator of cell proliferation, apoptosis and DNA damage response, and involved in the initiation and progression of human diseases. In this review, we summarize the current knowledge of lincRNA-p21, mainly focus on the known biological functions and its underlying mechanisms. Moreover, we highlight the growing body of evidences for the importance of lincRNA-p21 in diverse human diseases, which indicate lincRNA-p21 as a potential diagnostic marker and/or a valuable therapeutic target for these diseases.

The association of APOC4 polymorphisms with premature coronary artery disease in a Chinese Han population.

BACKGROUND: Hypercholesterolemia arising from abnormal lipid metabolism is one of the critical risk factors for coronary artery disease (CAD), however the roles of genetic variants in lipid metabolism-related genes on premature CAD (≤ 60 years old) development still require further investigation. We herein genotyped four single nucleotide polymorphisms (SNPs) in lipid metabolism-related genes (rs1132899 and rs5167 in APOC4, rs1801693 and rs7765781 in LPA), aimed to shed light on the influence of these SNPs on individual susceptibility to early-onset CAD. METHODS: Genotyping of the four SNPs (rs1132899, rs5167, rs1801693 and rs7765781) was performed in 224 premature CAD cases and 297 control subjects (≤ 60 years old) using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. The association of these SNPs with premature CAD was performed with SPSS software. RESULTS: Multivariate logistic regression analysis showed that C allele (OR = 1.50, P = 0.027) and CC genotype (OR = 2.84, P = 0.022) of APOC4 rs1132899 were associated with increased premature CAD risk, while the other three SNPs had no significant effect. Further stratified analysis uncovered a more evident association with the risk of premature CAD among male subjects (C allele, OR = 1.65, and CC genotype, OR = 3.33). CONCLUSIONS: Our data provides the first evidence that APOC4 rs1132899 polymorphism was associated with an increased risk of premature CAD in Chinese subjects, and the association was more significant among male subjects.