Analysis on the polymorphisms of site RS4977574, and RS1333045 in region 9p21 and the susceptibility of coronary heart disease in Chinese population

Abstract

Background: Rs4977574 (A > G) and Rs1333045 (C > T) are both single nucleotide polymorphisms (SNPs) related with coronary artery disease, locating on chromosome 9p21.3. The study aimed to identify the correlation between rs4977574 and rs1333045 polymorphism genotypes and coronary heart disease (CHD) in a Chinese population. Methods: Blood samples were collected from 855 subjects. A case-control study was used in this experiment, and 598 cases in the CHD group and 257 subjects in the control group were enrolled. Genotyping was identified by the Agena MassARRAY system. Statistical analysis was conducted by SPSS (Ver 16.0) and plink (Ver. 1.07, Shaun Purcell). Haplotype analysis was performed using Haploview software. Results: Association analysis by plink indicated a significant difference in the allele distribution for single nucleotide polymorphisms between cases and controls (rs4977574 P = 0.003, rs1333045 P = 0.035). Fisher's exact test by plink proved that allele G may be associated with a higher risk of CHD (P = 0.003, odds ratio (OR) = 1.371) and the T allele was likely to reduce the risk of coronary events (P = 0.035, OR = 0.798). The serum levels of apolipoprotein A (ApoA) were higher in subjects with the AG + AA genotype of rs4977574 compared to those with the GG genotype (P = 0.028). In the dominant model of rs1333045, the levels of ApoA were higher and LDL levels were lower in the TC + TT genotype than in the CC genotype. Conclusions: The present study examined the association between the 9p21 chromosome rs4977574 and rs1333045 polymorphism genotypes and CHD in a population of Chinese patients. The G allele of rs4977574 and the C allele of rs1333045 are the susceptibility sites of CHD.

CDKN2B‐AS1 gene rs4977574 A/G polymorphism and coronary heart disease: A meta‐analysis of 40,979 subjects

“…The information was drawn out from 18,430 CHD cases and 22,549 controls (Table 1 ). 9 , 10 , 11 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 Of the 35 obtained literatures after the preliminary search course, 17 met the present meta‐analysis including criteria. Among the eighteen eliminated papers, five of them were of review character.…”

“… 9 Analogously, in 2020, Hua et al examined the association between CDKN2B ‐ AS1 gene rs4977574 polymorphism and CHD in a Chinese population and found that the G allele is the CHD susceptibility site. 10 On the contrary, in 2007, Samani et al 11 reported that the G allele frequency was greatly lower in CHD patients than that in controls in a WTCCC study of a British population.…”

“…In 2013, Sakalar et al found that the G allele frequency of CDKN2B ‐ AS1 gene rs4977574 polymorphism in myocardial infarction patients was significantly higher than that in controls in a Turkish population 9 . Analogously, in 2020, Hua et al examined the association between CDKN2B ‐ AS1 gene rs4977574 polymorphism and CHD in a Chinese population and found that the G allele is the CHD susceptibility site 10 . On the contrary, in 2007, Samani et al 11 reported that the G allele frequency was greatly lower in CHD patients than that in controls in a WTCCC study of a British population.…”

Effect of 9p21.3 (lncRNA and CDKN2A/2B) variant on lipid profile

“…After the screening, 4,131 articles were excluded by their title and abstract. Next, 55 articles were further estimated by their contents, of which 5 articles provided lipid data by the genotypes of rs1333049 ( 39 , 40 ), rs4977574 ( 41 ), rs10757274 ( 42 ), and rs10811661 ( 43 ) but expressed as a median and interquartile range (IQR), 3 articles provided lipid data by the genotypes of rs1333049 but human subjects used lipid-lowering drugs ( 44 – 46 ), 2 articles provided the percentage change of lipid data by the genotypes of rs1333049 ( 47 , 48 ), 1 article did not present genotype counts of rs1333049 ( 17 ), and 1 article ( 49 ) provided lipid levels by the genotypes of rs1333049 but in an aberrant genetic model [(CG + GG) vs. CC]. Therefore, 12 articles were further excluded.…”

Analysis of the Correlation between the Level of Serum Inflammatory Factors and the Degree and Diagnosis of Coronary Artery Disease

“…The up-regulation of hs-CRP mainly affects the spasm of coronary artery vessels and the deposition of subendothelial adipose tissue. In turn, it affects the stenosis of vascular lumen, leading to cardiomyocyte ischemia and the occurrence of CHD [19][20][21][22] . In the process of increasing the number of coronary artery lesions, the expression of hs-CRP also increased significantly, suggesting that there may be a potential relationship between the expression of hs-CRP and the number of coronary artery lesions, mainly because the change of the expression concentration of hs-CRP can increase the risk of low density lipoprotein and triglyceride deposition, resulting in an increase in the risk of coronary artery branch occlusion in patients [23][24][25] .…”