Ying-Ying Zheng

Personalized antiplatelet therapy according to CYP2C19 genotype after percutaneous coronary intervention: A randomized control trial

OBJECTIVE The objective of this study is to compare personalized antiplatelet therapy according to CYP2C19 phenotype with conventional antiplatelet therapy in patients after percutaneous coronary intervention (PCI). METHODS A total of 600 patients with coronary artery disease (CAD) undergoing PCI randomly received a personalized antiplatelet therapy (group A; n=301) or conventional antiplatelet treatment (group B; n=299). For group A, antiplatelet therapy was performed according to CYP2C19 phenotype. For group B, the patients received conventional antiplatelet treatment without detected CYP2C19 genotype. The primary end point was compared between these two groups. This study is registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001807). RESULTS The primary end point occurred in 27 patients assigned to conventional treatment as compared with 8 patients assigned to personalized therapy (cumulative event rate, 9.03% vs. 2.66%; P<0.01). The composite rate of death, myocardial infarction, or stroke at 180 days occurred in 3 and 18 patients in the two groups, respectively (cumulative event rate, 1.0% and 6.2%, P<0.01). The cumulative 180-day incidence of ST was significantly lower in group A than in group B (0.66% vs. 3.01%, P=0.032). The 180-day incidence of MI (0.33% vs. 3.01%, P=0.011) and death (0.33% vs. 2.34%, P=0.011) was fewer than that in control, respectively. We did not find the significant difference in bleeding events between the 2 groups. CONCLUSION Personalized antiplatelet therapy according to CYP2C19 genotype after PCI can significantly decrease the incidence of major adverse cardiovascular events and the risk of 180-day ST in Chinese population.

Polymorphisms in the SAA1 gene are associated with ankle-to-brachial index in Han Chinese healthy subjects

Abstract Objective. Recent study suggested that the genetic polymorphisms of serum amyloid A protein (SAA) were linked to cardiovascular disease (CVD). However, the relationship between genetic polymorphisms of SAA and ankle-to-brachial index (ABI) in healthy subjects has not been studied. We investigated the role of the SAA1 gene polymorphisms with ABI. Methods and results. All participants were selected from a cohort of healthy subjects participating in the Cardiovascular Risk Survey (CRS) study. Four single-nucleotide polymorphisms (SNPs; rs12218, rs4638289, rs7131332 and rs11603089) were genotyped by use of polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. There was significant difference between CC genotype and CT genotype [(1.066 ± 0.113) vs (1.119 ± 0.096), p = 0.008], CC genotype and TT genotype [(1.066 ± 0.113) vs (1.127 ± 0.095), p = 0.002] of rs12218 in ABI, and these differences remained significant after adjustment for the sex, age, blood pressure, BMI, alcohol intake, smoking and high-density lipoprotein (HDL) [(1.073 ± 0.018) vs (1.122 ± 0.007), p = 0.012; (1.073 ± 0.018) vs (1.124 ± 0.006), p = 0.009), respectively]. These relationships were not found in rs874957, rs7950019 and rs11603089 before and after multivariate adjustment. Conclusions. CC genotype of rs12218 in the SAA1 gene was associated with decreased ABI in Chinese Han subjects, which indicated that the carriers of CC genotype of rs12218 have high risk of peripheral arterial disease.

Type 2 diabetes in Xinjiang Uygur autonomous region, China.

Background The aim of this study was to estimate the prevalence and distribution of type 2 diabetes and to determine the status of type 2 diabetes awareness, treatment, and control in Xinjiang, China. Our data came from the Cardiovascular Risk Survey (CRS) study designed to investigate the prevalence and risk factors for cardiovascular diseases in Xinjiang from October 2007 to March 2010. A total of 14 122 persons (5583 Hans, 4620 Uygurs, and 3919 Kazaks) completed the survey and examination. Diabetes was defined by the American Diabetes Association 2009 criteria. Methodology/Principal Findings Overall, 9.26% of the Han, 6.23% of the Uygur, and 3.65% of the Kazak adults aged ≥35 years had diabetes. Among diabetes patients, only 53.0% were aware of their blood glucose level, 26.7% were taking hypoglycemic agents, and 10.4% achieved blood glucose control in Han, 35.8% were aware of their blood glucose level, 7.3% were taking hypoglycemic agents, and 3.13% achieved blood glucose control in Uygur, and 23.8% were aware of their blood glucose level, 6.3% were taking hypoglycemic agents, and 1.4% achieved blood glucose control in Kazak, respectively. Conclusions/Significance Our results indicate that diabetes is highly prevalent in Xinjiang. The percentages of those with diabetes who are aware, treated, and controlled are unacceptably low. These results underscore the urgent need to develop national strategies to improve prevention, detection, and treatment of diabetes in Xinjiang, the west China.

Relationship between a Novel Polymorphism of the C5L2 Gene and Coronary Artery Disease

Background C5L2 has been demonstrated to be a functional receptor of acylation-stimulating protein (ASP), which is a stimulator of triglyceride synthesis or glucose transport. However, little is known about the variations in the coding region of the C5L2 gene and their association with coronary artery disease (CAD). Methodology/Principal Findings We identified a novel single nucleotide polymorphism (SNP), 698C>T (P233L), in exon 2 using a polymerase chain reaction direct-sequencing method. This nucleotide change causes the amino-acid order from proline to leucine at codon 233. We examined the role of this SNP for CAD using two independent case–control studies: one was in the Han population (492 CAD patients and 577 control subjects) and the other was in the Uygur population (319 CAD patients and 554 control subjects). Heterozygote carriers of the 698CT genotype were more frequent among CAD patients than among controls not only in the Han population (7.3% versus 1.7%) but also in the Uygur population (4.7% versus 1.6%). The odds ratio (OR) for carriers of the 698CT genotype for CAD was 4.484 (95% confidence interval (CI): 2.197–9.174) in the Han group and 2.989 (95% CI: 1.292–6.909) in the Uygur population. After adjustment of confounding factors such as sex, age, smoking, alcohol consumption, hypertension, diabetes, as well as serum levels of triglyceride, total cholesterol, high-density lipoprotein, the difference remained significant in the Han group (P<0.001, OR = 6.604, 95% CI: 2.776–15.711) and in the Uygur group (P = 0.047, OR = 2.602, 95% CI: 1.015–6.671). Conclusion/Significance The 698CT genotype of C5L2 may be a genetic maker of CAD in the Han and Uygur population in western China.

Alcohol consumption and carotid atherosclerosis in China: the Cardiovascular Risk Survey.

Aim: The relationship between alcohol consumption and carotid atherosclerosis has been reported in some epidemiological studies, but the results were conflicting. We investigated the association between alcohol intake and carotid atherosclerosis in the Han, Uygur, and Kazakh populations in Xinjiang in western China. Methods and results: The study population sample comprised 13,037 Chinese people (5277 Han, 4572 Uygur, and 3188 Kazakh) aged ≥35 years who participated in a cardiovascular risk survey between June 2007 and March 2010. Daily consumption of alcohol was determined by the number and frequency of alcoholic beverages consumed. Carotid-artery parameters, including common carotid artery intima–media thickness (CCA–IMT) and carotid plaques were measured using high-resolution B-mode ultrasonography. In the Han and Kazakh populations, CCA–IMT as a function of alcohol consumption was depicted as a J-shaped curve with a nadir for the alcohol-intake category of 20–29.9 g/day; In the Uygur population, a similar curve with a nadir of 30–49.9 g/day was observed. With respect to the prevalence of carotid plaques, we also observed similar curves in the Han and Kazakh populations, but not in the Uygur population. After adjustment for age, sex, blood pressure, body mass index, and smoking status, as well as levels of glucose, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol, the J-shaped curves remained. Conclusions: Our results indicated that alcohol consumption was associated with carotid atherosclerosis and that moderate drinking had an inverse association with carotid atherosclerosis. However, the definition of moderate drinking could be different in Han, Uygur, and Kazakh populations.

CYP2C19 Phenotype, Stent Thrombosis, Myocardial Infarction, and Mortality in Patients with Coronary Stent Placement in a Chinese Population

Background Several studies have indicated that CYP2C19 loss-of-function polymorphisms have a higher risk of stent thrombosis (ST) after percutaneous coronary interventions (PCIs). However, this association has not been investigated thoroughly in a Chinese population. In this study, we aimed to determine the effect of CYP2C19*2 and CYP2C19*3 loss-of-function polymorphisms on the occurrence of ST and other adverse clinical events in a Chinese population. Methods We designed a cohort study among 1068 consecutive patients undergoing intracoronary stent implantation after preloading with 600 mg of clopidogrel. CYP2C19*2 and CYP2C19*3 were genotyped by using polymerase chain reaction-restriction fragment length polymorphism analysis. The adverse clinical events recorded were ST, death, myocardial infarction (MI), and bleeding events. The primary end point of the study was the incidence of cumulative ST within 1 year after PCI. The secondary end point was other adverse clinical outcomes 1 year after the procedure. Results The cumulative 1-year incidence of ST was 0.88% in patients with extensive metabolizers (EMs) (CYP2C19*1/*1 genotype), 4.67% in patients with intermediate metabolizers (IMs) (CYP2C19*1/*2 or *1/*3 genotype), and 10.0% in patients with poor metabolizers (PMs) (CYP2C19*2/*2, *2/*3, or *3/*3 genotype) (P<0.001). The one-year event-free survival was 97.8% in patients with EMs, 96.5% in patients with IMs, and 92.0% in patients with PMs (P = 0.014). Multivariate analysis confirmed the independent association of CYP2C19 loss-of-function allele carriage with ST (P = 0.009) and total mortality (P<0.05). Conclusion PM patients had an increased risk of ST, death, and MI after coronary stent placement in a Chinese population.

Haplotype study of the CYP4A11 gene and coronary artery disease in Han and Uygur populations in China

BACKGROUND CYP4A11 converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), which has a crucial role in the modulation of cardiovascular homeostasis. We assessed the association between the human CYP4A11 gene and coronary artery disease (CAD) in Han and Uygur populations in China. METHODS AND RESULTS In the Han population, 361 CAD patients and 315 controls were genotyped for four single-nucleotide polymorphisms (SNPs) of the human CYP4A11 gene (rs9332978, rs4660980, rs3890011, rs1126742). In the Uygur population, 331 CAD patients and 182 controls were genotyped for the same four SNPs. Data were assessed via haplotype-based case-control studies. For the Han population, the significance of the recessive model of SNP3 (GG vs. CC+GC) between CAD patients and control subjects was retained after adjustment for EH, DM and smoking (for men, 95% CI: 1.173-3.013, P=0.009). The G-G-T haplotype in CAD was significantly higher than that in the control group (P=0.037). In the Uygur population, neither the distribution of genotypes and alleles for the four SNPs nor the distribution of haplotypes constructed with the same three SNPs showed a significant difference between CAD and control subjects. CONCLUSIONS The GG genotype of rs3890011 and the G-G-T haplotype in the CYP4A11 gene could be a useful genetic marker of CAD in Han populations in China.

Serum uric acid levels are associated with polymorphism in the SAA1 gene in Chinese subjects.

Objective Serum uric acid (SUA) is a cardiovascular risk marker associated with inflammation. The serum amyloid A protein (SAA) is an inflammatory factor and is associated with cardiovascular disease (CVD). However, the relationship between genetic polymorphisms of SAA and SUA levels has not been studied. The objective of this study was to investigate the association between SUA levels and SAA genetic polymorphisms. Methods All participants were selected from subjects participating in the Cardiovascular Risk Survey (CRS) study. The single nucleotide polymorphism (SNP) rs12218 of the SAA1 gene was genotyped by using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. The association of SUA levels with genotypes was assessed by using the general liner mode. Results The SNP rs12218 was associated with SUA levels by analyses of a dominate model (P = 0.002) and additive model (P = 0.005), and the difference remained significant after adjustment of sex, age, obesity, ethnicity, HDL-C, alcohol intake, smoking, and creatinine (P = 0.006 and P = 0.023, respectively). The TT genotype was associated with an increased SUA concentration of 39.34 mmol/L (95% confidence interval [CI], 3.61–75.06, P = 0.031) compared with the CC genotype, and the TT genotype was associated with an increased SUA concentration of 2.48 mmol/L (95% CI, 6.86–38.10; P = 0.005) compared with the CT genotype. Conclusions The rs12218 SNP in the SAA1 gene was associated with SUA levels in Chinese subjects, indicating that carriers of the T allele of rs12218 have a high risk of hyperuricemia.

−94 ATTG Insertion/Deletion Polymorphism of the NFKB1 Gene Is Associated with Coronary Artery Disease in Han and Uygur Women in China

OBJECTIVES The nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) signaling pathway plays a key role in the regulatory network of inflammation. The deletion variant allele of the NFKB1-94 insertion/deletion (ins/del) ATTG promoter polymorphism results in lower transcription levels of the p50 subunit, and the variant allele has been associated with several inflammatory diseases as well as with coronary artery disease (CAD) with inflammation playing an important part in the pathogenesis. The aim of the present study was to assess the association between the human NFKB1 gene polymorphism and CAD in a Han and Uygur population of China. METHODS We used the following two independent case-control studies: a Han population (633 CAD patients and 616 control subjects) and a Uygur population (437 CAD patients and 356 control subjects). All participants were genotyped for the same one single nucleotide polymorphism (SNP) (rs28362491) of the NFKB1 gene, that is, DD, ATTG deleted homozygote; ID, ATTG inserted and deleted heterozygote and II, ATTG inserted homozygote by real-time polymerase chain reaction. RESULTS The distribution of the SNP (rs28362491) genotypes was significantly different between CAD and control participants in women of the Han (p=0.029) and the Uygur (p=0.032) populations, but not in men. Further, DD carriers of the SNP in the NFKB1 gene were more frequent in female CAD patients than in controls in both the Han (23.2% vs. 13.5%, p=0.009) and the Uygur (19.8% vs. 8.3%, p=0.012) population. The significant difference between DD and ID+II genotypes was retained after adjustment for covariates (for Han, odds ratio [OR]: 1.805, p=0.029 and for Uygur, OR: 3.192, p=0.011). CONCLUSIONS The DD genotype of the SNP (rs28362491) in the NFKB1 gene may be considered a genetic marker of CAD in Han and Uygur women in China.

CYP4A11 gene T8590C polymorphism is associated with essential hypertension in the male western Chinese Han population

Abstract Background: CYP4A11 is a member of the cytochrome P450 enzymes and is responsible for metabolizing arachidonic acid to 20-hydroxyeicosatetraenoic acid, a metabolite involved in the regulation of blood pressure. This study aimed to evaluate whether or not the CYP4A11 gene polymorphism T8590C (rs1126742) is involved in essential hypertension in the western Chinese Han population. Methods: In a case-control study, the participants included 864 (523 males and 341 females) patients with essential hypertension and 661 (422 males and 239 females) healthy subjects. The T8590C polymorphism of the CYP4A11 gene was analyzed by using the TaqMan® SNP Genotyping Assay. Results: For men, the frequencies of the CC genotype and the C allele were higher in essential hypertension than in the control group (p = 0.022 and p = 0.016, respectively). After adjustment of confounding factor such as diabetes, smoking, BMI, TG and TC, the significant difference was observed in CC genotype (OR = 1.897, 95% confidence interval [CI] 1.026–3.508; p = 0.041). No difference was found in all participants and females. Conclusions: The CC genotype and C allele were associated with essential hypertension in the male western Chinese Han population.