Yi-Tong Ma

Polymorphisms in the SAA1/2 Gene Are Associated with Carotid Intima Media Thickness in Healthy Han Chinese Subjects: The Cardiovascular Risk Survey

Background Serum amyloid A protein (SAA) is not only an inflammatory factor, but also an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of high-density lipoprotein (HDL), which has been linked to atherosclerosis. However, the relationship between genetic polymorphisms of SAA and the intima-media thickness (IMT) of the common carotid artery in healthy subjects remains unclear. We investigated the role of SAA1 and SAA2 gene polymorphisms with IMT in a cohort of healthy subjects participating in the Cardiovascular Risk Survey (CRS) study. Methodology/Principal Findings Anthropometric and B-mode ultrasound of the carotid IMT were measured in 1914 subjects (849 men; 1065 women) recruited from seven cities in Xinjiang province, (western China). Four SNPs (rs12218, rs2229338, rs1059559, and rs2468844) were genotyped by use of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The SNP rs12218 was associated with carotid IMT by analyses of a dominate model (P<0.001) and additive model (P = 0.003), and the difference remained significant after multivariate adjustment (P = 0.008, P<0.001, respectively). This relationship was also observed in rs2468844 after multivariate adjustment by recessive model analysis (P = 0.011) but this was not observed in rs2229338 and rs1059559 before and after multivariate adjustment. These associations were not modified by serum HDL concentration. Furthermore, there were significant interactions between rs2468844 and rs12218 (interaction P<0.001) and rs2229338 (interaction P = 0.001) on carotid IMT. Conclusion/Significance Both rs12218 of the SAA1 gene and rs2468844 of SAA2 gene are associated with carotid IMT in healthy Han Chinese subjects.

Haplotype Analysis of the CYP8A1 Gene Associated With Myocardial Infarction

Objective: The aim of this study was to assess the association between the human CYP8A1 gene and myocardial infarction (MI) in Chinese people. Methods: 210 MI patients and 206 age-matched controls were genotyped and constructed haplotypes for 3 SNPs [3982C>T (rs5602), C1117A (rs5629), C251T (rs454-98106)] of the human CYP8A1 gene. Results: The CC genotype of rs5629 was more frequently in MI patients than in control subjects (P = .030). The frequency of the A-C-T haplotype was significantly higher in MI patients than in control subjects (P =.001). The frequency of the C-T-T haplotype was significantly lower in MI patients than in control subjects (P= .011). Conclusions: The present results indicate that MI is associated with the CC genotype of rs5629 in the human CYP8A1 gene. The A-C-T haplotype appears to be a useful genetic marker and the C-T-T haplotype might be a protective factor of MI in Chinese people.

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.

Alcohol consumption and ankle-to-brachial index: results from the Cardiovascular Risk Survey.

Background and Methodology A low ankle-to-brachial index (ABI) is a strong correlate of cardiovascular disease and subsequent mortality. The relationship between ABI and alcohol consumption remains unclear. Data are from the Cardiovascular Risk Survey (CRS), a multiple-ethnic, community-based, cross-sectional study of 14 618 Chinese people (5 757 Hans, 4 767 Uygurs, and 4 094 Kazakhs) aged 35 years and over at baseline from Oct. 2007 to March 2010. The relationship between alcohol intake and ABI was determined by use of analysis of covariance and multivariable regressions. Principal Findings In men, alcohol consumption was significantly associated with ABI (P<0.001). After adjusted for the confounding factors, such as age, sex, ethnicity, body mass index, smoking, work stress, diabetes, and fasting blood glucose, the difference remained significant (P<0.001); either the unadjusted or multivariate-adjusted odds ratio (OR) for peripheral artery disease (PAD) was significantly higher in men who consumed >60.0 g/d [OR  = 3.857, (95% CI: 2.555–5.824); OR = 2.797, (95% CI: 1.106–3.129); OR = 2.878, (95% CI: 1.215–4.018); respectively] and was significantly lower in men who consumed 20.1–40.0 g/d [OR  = 0.330, (95% CI: 0.181–0.599); OR = 0.484, (95% CI: 0.065–0.894); OR = 0.478, (95% CI: 0.243–1.534); respectively] and 40.1–60.0 g/d [OR  = 0.306, (95% CI: 0.096–0.969); OR = 0.267, (95% CI: 0.087–0.886); OR = 0.203, (95% CI: 0.113–0.754); respectively] compared with never drinking, respectively (all P<0.01). Neither in unadjusted nor in multivariate-adjusted model was the association between ABI and alcohol consumption significant (all P>0.05) in women. Similarly, PAD was not correlated with alcohol intake in women (all P>0.05). Conclusions/Significance Our results indicated that in Chinese men, alcohol consumption was associated with peripheral artery disease, and consumption of less than 60 g/d had an inverse association with peripheral atherosclerosis whereas consumption of 60 g/d or more had a positive association.

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.

A haplotype of the CYP4A11 gene associated with essential hypertension in Japanese men

Objective CYP4A11, a member of the cytochrome P450 family, acts mainly as an enzyme that converts arachidonic acid to 20-hydroxyeicosatetraenoic acid, a metabolite involved in blood pressure regulation in humans. Disruption of the murine cyp4a14 and cyp4a10 genes, homologues of human CYP4A11, was reported recently to cause hypertension. The gene-disrupted male mice had higher blood pressure than the gene-disrupted female mice. The present study aimed to assess the association between the human CYP4A11 gene and essential hypertension, using a haplotype-based case–control study including separate analysis of the gender groups. Methods The 304 essential hypertension patients and 207 age-matched control individuals were genotyped for three single-nucleotide polymorphisms of the human CYP4A11 gene (rs2269231, rs1126742, rs9333025). Data were assessed for three separate groups: total participants, men and women. Results For total participants, the genotypic distribution of rs1126742 differed significantly between the two groups (P = 0.005). For total participants, men and women, the recessive model (CC versus TC + TT) of rs1126742 differed significantly between the two groups (P = 0.007, P = 0.043, and P = 0.045, respectively). Logistic regression analysis showed the TC + TT genotype was significantly higher in essential hypertension patients than in control individuals for total participants and men (P = 0.022 and P = 0.043, respectively). The A-T-G haplotype frequency (established by rs2269231, rs1126742, rs9333025) was significantly higher in essential hypertension men than in control men (P = 0.043). Conclusions Essential hypertension is associated with the TC + TT genotype of rs1126742 in the human CYP4A11 gene. The A-T-G haplotype appears a useful genetic marker of essential hypertension in Japanese men.

Acupuncture for essential hypertension: a meta-analysis of randomized sham-controlled clinical trials.

Background. Acupuncture is frequently advocated as an adjunct treatment for essential hypertension. The aim of this review was to assess its adjunct effectiveness in treating hypertension. Methods. We searched PubMed, the Cochrane Library, EMBASE, and the Chinese databases Sino-Med, CNKI, WanFang, and VIP through November, 2012, for eligible randomized controlled trials that compared acupuncture with sham acupuncture. Outcome measures were changes in diastolic (DBP) and systolic blood pressure (SBP). Results. A total of 4 randomized controlled trials were included. We found no evidence of an improvement with the fact that acupuncture relative to sham acupuncture in SBP change (n = 386; mean difference = −3.80 mmHg, 95% CI = −10.03–2.44 mmHg; I 2 = 99%), and an insignificant improvement in DBP change (n = 386; mean difference = −2.82 mmHg, 95% CI = −5.22–(−0.43) mmHg; I 2 = 97%). In subgroup analyses, acupuncture significantly improved both SBP and DBP in patients taking antihypertensive medications. Only minor acupuncture-related adverse events were reported. Conclusions. Our results are consistent with acupuncture significantly lowers blood pressure in patients taking antihypertensive medications. We did not find that acupuncture without antihypertensive medications significantly improves blood pressure in those hypertensive patients.

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.

A Haplotype of the CYP4F2 Gene is Associated With Cerebral Infarction in Japanese Men

BACKGROUND CYP4F2, a member of the cytochrome P450 family, acts mainly as an enzyme and is involved not only in the metabolism of leukotriene B4, but also in that of arachidonic acid. It converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite involved in the regulation of the vascular tone in the brain. The aim of this study was to assess the association between the human CYP4F2 gene and cerebral infarction (CI), using a haplotype-based case-control study with separate analyses of data from the gender groups. METHODS A total of 175 CI patients and 246 control subjects were genotyped for five single-nucleotide polymorphisms (SNPs) of the human CYP4F2 gene (rs3093105, rs3093135, rs1558139, rs2108622, rs3093200). For data analysis, three separate groups were assessed: all subjects, men, and women. RESULTS In the male subjects, the G allele frequency for rs2108622 was significantly higher in CI patients as compared to control subjects (P = 0.025). The overall distribution of the haplotypes in the men was significantly different between the CI patients and the control subjects (P = 0.027). Additionally, the frequency of the T-C-G haplotype for men was significantly higher in the CI patients than in the control subjects (P = 0.008). Multiple logistic regression analysis also revealed the significance of the T-C-G haplotype in men, even after adjustment for confounding factors. CONCLUSIONS The results of this study indicate that, in Japanese men, CI is associated with the G allele of rs2108622 and, in addition, that the T-C-G haplotype appears to be a useful genetic marker for CI.

Association of polymorphisms of PTGS2 and CYP8A1 with myocardial infarction.

Abstract Background: Cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS) are enzymes involved in prostaglandin and prostacyclin synthesis, which have been linked to cardiovascular disease risk. We hypothesized that genetic variations altering the function of these enzymes would modify the risk of myocardial infarction (MI). Methods: In a Chinese case control study of MI patients (n=356) and healthy controls (n=350), we investigated the roles of polymorphisms in the PGIS gene (CYP8A1) and the COX-2 gene (PTGS2) using polymerase chain reaction-restriction fragment length polymorphism analysis. Results: The CC genotype of CYP8A1 and the –765CC genotype of PTGS2 were more common in the MI patients than in the control subjects (p=0.041, p=0.012, respectively). The odds ratio (OR) estimated by the combined analysis for the CYP8A1 CC and PTGS2 –765CC genotypes [OR=5.44; 95% confidence interval (CI): 3.12–7.23] was markedly higher than that estimated separately for the CYP8A1 CC genotype (OR=1.37; 95% CI: 0.95–2.85) or the PTGS2 –765CC genotype (OR=2.92; 95% CI: 1.78–5.76) alone. Conclusions: The CC genotype of CYP8A1 or the –765CC genotype of PTGS2 is associated with MI, respectively. Furthermore, the significantly combined effects of these two gene variants in the arachidonic acid metabolic pathway indicate that combining the effects of a modest number of genes, whose products are known to act in a pathophysiological manner, could be a useful method to explore the association of genetic polymorphisms and polygenic inheritance disease. Clin Chem Lab Med 2009;47:347–52.