ABCA1 variants rs2230806 (R219K), rs4149313 (M8831I), and rs9282541 (R230C) are associated with susceptibility to coronary heart disease

Wang, Fangfang; Ji, Yuan; Chen, Xin; Song, Ying; Huang, Shenglan; Zhou, Chun‐Gao; Huang, Changgen; Chen, Zengguang; Zhang, Liangfeng; Ge, Jianli

doi:10.1002/jcla.22896

Cited by 19 publications

(15 citation statements)

References 24 publications

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“…Some studies have shown that ABCA1 rs4149313 is associated with coronary heart disease, 21,22 while we identified a significant association between rs4149313 and T2DM in three genetic models in this study. Conversely, while ABCB1 rs1128503 has previously been associated with hepatocellular carcinoma and breast cancer, 23,24 we found no association between rs1128503 and T2DM in this study.…”

Section: Discussionsupporting

confidence: 54%

Association between ABC family variants rs1800977, rs4149313, and rs1128503 and susceptibility to type 2 diabetes in a Chinese Han population

Yan

Luo

et al. 2020

J Int Med Res

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Objective To investigate the association between three single nucleotide polymorphisms (SNPs) of the ATP-binding cassette (ABC) gene family and susceptibility to type 2 diabetes mellitus in a Chinese Han population. Methods A total of 1086 type 2 diabetes patients and 1122 healthy controls were included in this retrospective study. Three genetic variants, rs1800977 and rs4149313 in ABCA1, and rs1128503 in ABCB1 were included in the study. Susceptibility to type 2 diabetes was evaluated under three genetic models. Results A significant association between rs1800977 and type 2 diabetes was identified in three different genetic models (TT vs CC, odds ratio [OR] = 0.611 [95% confidence interval (CI), 0.469–0.798]; T vs C, OR = 0.841 [95% CI, 0.745–0.950]; and the recessive model, OR = 0.606 [95% CI, 0.474–0.774]). Additionally, a significant association between rs4149313 and type 2 diabetes was identified in three different genetic models (AA vs GG, OR = 0.467 [95% CI, 0.326–0.670]; A vs G, OR = 0.819 [95% CI, 0.717–0.935]; and the recessive model, OR = 0.478 [95% CI, 0.336–0.680]). Conclusion We found that SNPs rs1800977 and rs4149313 in ABCA1 are significantly associated with susceptibility to type 2 diabetes in a Chinese population, although this should be confirmed in a larger study.

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Section: Discussionsupporting

confidence: 54%

Association between ABC family variants rs1800977, rs4149313, and rs1128503 and susceptibility to type 2 diabetes in a Chinese Han population

Yan

Luo

et al. 2020

J Int Med Res

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“…Genetic factors are key to an individual’s susceptibility to CHD, accounting for 30–60% of interindividual variation in the risk of CHD [7]. Some studies have shown genetic polymorphisms are associated with CHD risk in the Chinese populations, such as ABCA1 and paraoxonase 1 genes [8]. Among other risk factors are advanced age, diabetes, hypertension, increased total and low-density lipoprotein cholesterol in plasma, increased plasma triglycerides (TGs), and decreased plasma high-density lipoprotein (HDL) cholesterol [9].…”

Section: Introductionmentioning

confidence: 99%

<b><i>NT5C2</i></b> Gene Polymorphisms and the Risk of Coronary Heart Disease

Chen

Zhang

Wang

et al. 2020

Public Health Genomics

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Background: Increasing studies have reported that 5′-nucleotidase cytosolic II (NT5C2) has a strong relationship with coronary heart disease (CHD) development. This study was designed to examine the relationship between NT5C2 polymorphisms and CHD in the Chinese Han population. Methods: We studied 501 CHD patients and 496 healthy controls from the Second Affiliated Hospital of Hainan Medical University in Hainan Province, China. Four single nucleotide polymorphisms (SNPs) in NT5C2 were selected and genotyped using Agena MassARRAY technology. Odds ratios and 95% confidence intervals were calculated using logistic regression after adjusting for age and gender. Stratification analysis was performed by age and gender in all individuals; we especially investigated the effects of NT5C2 SNPs on hypertension and diabetes among CHD patients. Results: rs2148198 of NT5C2 was strongly associated with an increased risk of CHD (allele: p = 0.045; codominant: p = 0.007; additive: p = 0.016). Stratified analysis revealed that rs2148198 was associated with increased CHD risk in individuals aged ≤61 years and males. For CHD patients, rs2148198 significantly affected the risk of hypertension and diabetes (p < 0.05). Further, rs79237883 of NT5C2 was associated with decreased susceptibility to hypertension in multiple genetic models for individuals with CHD (allele: p = 0.007; codominant: p = 0.001; dominant: p = 0.001; additive: p = 0.008). Conclusion: This study reports the association of NT5C2 gene variants and CHD susceptibility in the Chinese Han population. Especially, NT5C2 rs2148198 was significantly associated with CHD risk in the subgroups of males, hypertension, and diabetes.

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“…The association between altered HDL concentrations and many other ABCA1 variants, including R219K (rs2230806) is well established by previous studies [ 76 , 77 , 78 ], which are linked to the development of ischemic heart disease (IHD) by the increasing risk of atherosclerosis in the general population [ 79 ]. According to recent studies, it has been revealed that the effects on plasma HDL cholesterol level and the incidence and severity of coronary heart diseases depend mostly on the distribution and frequency of SNPs in different regions of the ABCA1 gene as well as different populations [ 80 , 81 ]. Since similar SNPs show similar or opposite effects, widespread mutagenesis studies are required to investigate the exact role and the loss of function of ABCA1 upon G1050V and S1067C mutations.…”

Section: Discussionmentioning

confidence: 99%

Computational SNP Analysis and Molecular Simulation Revealed the Most Deleterious Missense Variants in the NBD1 Domain of Human ABCA1 Transporter

Dash

Ali

Rana

et al. 2020

IJMS

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The ATP-binding cassette transporter A1 (ABCA1) is a membrane-bound exporter protein involved in regulating serum HDL level by exporting cholesterol and phospholipids to load up in lipid-poor ApoA-I and ApoE, which allows the formation of nascent HDL. Mutations in the ABCA1 gene, when presents in both alleles, disrupt the canonical function of ABCA1, which associates with many disorders related to lipid transport. Although many studies have reported the phenotypic effects of a large number of ABCA1 variants, the pathological effect of non-synonymous polymorphisms (nsSNPs) in ABCA1 remains elusive. Therefore, aiming at exploring the structural and functional consequences of nsSNPs in ABCA1, in this study, we employed an integrated computational approach consisting of nine well-known in silico tools to identify damaging SNPs and molecular dynamics (MD) simulation to get insights into the magnitudes of the damaging effects. In silico tools revealed four nsSNPs as being most deleterious, where the two SNPs (G1050V and S1067C) are identified as the highly conserved and functional disrupting mutations located in the NBD1 domain. MD simulation suggested that both SNPs, G1050V and S1067C, changed the overall structural flexibility and dynamics of NBD1, and induced substantial alteration in the structural organization of ATP binding site. Taken together, these findings direct future studies to get more insights into the role of these variants in the loss of the ABCA1 function.

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ABCA1 variants rs2230806 (R219K), rs4149313 (M8831I), and rs9282541 (R230C) are associated with susceptibility to coronary heart disease

Cited by 19 publications

References 24 publications

Association between ABC family variants rs1800977, rs4149313, and rs1128503 and susceptibility to type 2 diabetes in a Chinese Han population

Association between ABC family variants rs1800977, rs4149313, and rs1128503 and susceptibility to type 2 diabetes in a Chinese Han population

<b><i>NT5C2</i></b> Gene Polymorphisms and the Risk of Coronary Heart Disease

Computational SNP Analysis and Molecular Simulation Revealed the Most Deleterious Missense Variants in the NBD1 Domain of Human ABCA1 Transporter

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