title: The risk of clopidogrel resistance is associated with ABCB1 polymorphisms but not promoter methylation in a Chinese Han population.
abstract: The goal of our study was to investigate the contribution of ABCB1 expression to the risk of clopidogrel resistance (CR). Platelets functions were measured using the Verify-Now P2Y12 assay. Applying Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), the single-nucleotide polymorphisms (SNPs) was tested. Using bisulphite pyrosequencing assay, we investigated the association of the ABCB1 DNA methylation levels and CR. It was shown that female, hypertension, and lower albumin levels increased the risk of CR (P<0.05). If patients did not have hypoproteinaemia or had hypertension, the SNP in rs1045642 was associated with CR (CC vs. TT: albumin ≥35, P = 0.042; hypertension, P = 0.045; C vs. T: albumin ≥35, P = 0.033; hypertension, P = 0.040). Additionally, the platelet inhibition of the CT+TT genotype in rs1128503 was larger than that of the CC genotype (P = 0.021). Multivariate logistic regression analysis showed that male, higher albumin and hsCRP decreased the risk of CR, and the stent size maybe positively correlated with CR. The SNP in rs1045642 was related to all-cause mortality (P = 0.024). We did not find any relationship between the methylation levels of the ABCB1 promoter and CR. In conclusions, our study indicated that ABCB1 polymorphisms might be useful in further evaluating the pathogenesis of CR.
authors.affiliation: Department of Gerontology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Traditional Chinese Internal Medicine, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Anaesthesia, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Gerontology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Hanbin
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Cardiology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Biochemistry, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Lindan
authors.initials: L
authors.lastname: Ji
authors.affiliation: The Key Laboratory of Molecular Medicine, Ningbo No. 1 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Maoqing
authors.initials: M
authors.lastname: Tong
authors.affiliation: Department of Gerontology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Gerontology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Gerontology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Jianjiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gerontology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Gerontology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Yezi
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Gerontology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Gerontology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Gerontology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Gerontology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People's Republic of China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Yu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000368:Aged; D000077144:Clopidogrel; D019175:DNA Methylation / Q000187:drug effects; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012709:Serum Albumin; D012727:Sex Characteristics; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D057772:Vascular System Injuries / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D010975:Platelet Aggregation Inhibitors; D012709:Serum Albumin; D000077144:Clopidogrel; D013988:Ticlopidine