Chromosome 9p21 and ABCA1 Genetic Variants and Their Interactions on Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population

Abstract

The single nucleotide polymorphisms (SNPs) related to both coronary heart disease (CHD) and ischemic stroke (IS) in Chinese individuals have not been identified definitely. This study was developed to evaluate the genetic susceptibility to CHD and IS on the chromosome 9p21 and the adenosine triphosphate (ATP)-binding cassette transporter A1 genes (ABCA1) in a Chinese Han population. Genotypes of the rs1333040, rs1333042, rs4977574, rs2066715 and rs2740483 SNPs were determined in 1134 unrelated patients (CHD, 565 and IS, 569) and 541 controls. The frequencies of the rs4977574 genotypes and alleles between CHD and control groups, and the rs2740483 genotypes and alleles between IS and control groups were different (p = 0.006–0.001). The subjects with rs1333042GG genotype and the carriers of the rs4977574G allele were associated with increased risk of CHD. The carriers of the rs4977574G allele were associated with increased risk of IS. However, the carriers of the rs2740483C allele had lower risk of IS than the non-carriers of the rs2740483C allele after controlling for potential confounders. The rs4977574GG-age (>60 year) interaction increased the risk of CHD (p = 0.022), whereas the rs2740483CG/CC-body mass index (>24 kg/m2) interaction decreased the risk of IS (p = 0.035). The interactions of rs1333040-rs1333042 on the risk of CHD and IS were relatively strong, whereas the interactions of rs1333040-rs1333042-rs2066715 and rs1333040-rs1333042-rs2066715-rs2740483 on the risk of CHD, and rs1333040-rs1333042-rs4977574 and rs1333040-rs1333042-rs4977574-rs2740483 on the risk of IS were relatively weak. These findings suggest that some common variants on the chromosome 9p21 and ABCA1 and their interactions may significantly modify the risk of CHD and IS independent of effects on serum lipid levels.

Association between the <i>MVK</i> rs2287218 SNP and the risk of coronary heart disease and ischemic stroke: A case-control study

“…The normal values of serum TC, TG, HDL-C, LDL-C, ApoA1, ApoB levels and the ApoA1/ApoB ratio in our Clinical Science Experiment Center were 3.10-5.17, 0.56-1.70, 0.91-1.81, 2.70-3.20 mmol/L; 1.00-1.78, 0.63-1.14 g/L; and 1.00-2.50; respectively (24). The individuals with TC > 5.17 mmol/L and/or TG covariance analysis (ANCOVA).…”

DOCK7-ANGPTL3 SNPs and their haplotypes with serum lipid levels and the risk of coronary artery disease and ischemic stroke

“…The normal values in our Clinical Science Experiment Center were 3.10-5.17 mmol/L for TC, 0.56–1.70 mmol/L for TG, 0.91–1.81 mmol/L for HDL-C, 2.70–3.20 mmol/L for LDL-C, 1.00–1.78 g/L for ApoA1, 0.63–1.14 g/L for ApoB, and 1.00–2.50 for the ApoA1/ApoB ratio. The participants with TC > 5.17 mmol/L, and/or TG > 1.70 mmol/L were defined as hyperlipidemic [ 24 , 25 ]. Hypertension was defined as a systolic blood pressure of 140 mmHg or greater, and/or a diastolic blood pressure of 90 mmHg or higher [ 26 ].…”

“…Genomic DNA was extracted from leucocytes of venous blood using the phenol-chloroform method. Genotyping of the SNPs was accomplished by the Snapshot technology platform in the Center for Human Genetics Research, Shanghai Genesky Bio-Tech Co. Ltd. [ 25 , 27 – 29 ]. The restriction enzymes for the loci were SAP (Promega) and Exonucleasel (Epicentre).…”

ANRIL polymorphism rs4977574 is associated with increased risk of coronary artery disease in Asian populations

“…However, the associations between rs4977574 and the risk of CAD are likely to be varied across different ethnicities. To date, most of the studies on ANRIL rs4977574 polymorphism focused on Caucasians, [ 17 , 20 , 21 ] and few studies are available on Asians. Huang et al carried out a case-control study of 590 Chinese CAD patients and 482 non-CAD patients subjects and found that ANRIL rs4977574 polymorphism was associated with a significantly increased risk of CAD in females (χ 2 = 10.29, P = .003, OR = 2.14, 95% CI 1.31–2.77).…”

“…Huang et al carried out a case-control study of 590 Chinese CAD patients and 482 non-CAD patients subjects and found that ANRIL rs4977574 polymorphism was associated with a significantly increased risk of CAD in females (χ 2 = 10.29, P = .003, OR = 2.14, 95% CI 1.31–2.77). [ 22 ] Additional studies on Chinese, Japanese and people from other Asian countries also suggested that ANRIL rs4977574 polymorphism was associated with an increased CAD risk, [ 16 , 17 , 21 , 23 – 24 ] but hitherto, no meta-analysis of ANRIL rs4977574 polymorphism and CAD risk is available. In the present study, we carried out a meta-analysis of the overall effect of ANRIL polymorphism rs4977574 (A >G) on CAD risk in Asian subjects.…”