Ding Huang

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.

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.

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.

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.

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.

Interaction between COX-2 G-765C and smoking in relation to coronary artery disease in a Chinese Uighur population.

Abstract Background: Coronary artery disease (CAD) is a complex multifactorial and polygenic disorder where multiple environmental and genetic factors are involved simultaneously. The purpose of this study was to explore the relationship between the interaction of cyclooxygenase-2 (COX-2) gene polymorphism and smoking and CAD in a Uighur population. Methods: Using a case-control study of Chinese Uighur CAD patients (n=430) and healthy controls (n=470), we investigated the roles of G-765C polymorphism in the COX-2 gene (PTGS2) by the use of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The PTGS2 GG genotype was significantly more prevalent in CAD patients (84.6% vs. 78.3%; p=0.014). Multiple logistic regression analysis showed two independent risk factors: smoking (OR 1.89, 95% CI 1.01–5.24; p=0.008) and hypertension (OR 2.73, 95% CI 1.59–7.21; p=0.001). Moreover, there was a synergistic effect between smoking and the PTGS2 polymorphism and the occurrence of CAD (interaction p=0.009). The odds ratio (OR) estimated by the combined analysis of the PTGS2 GG genotype and smoking history (OR 4.09, 95% CI 2.7–9.3) was markedly higher than that estimated separately from the PTGS2 GG genotype (OR 1.28, 95% CI 0.8–1.9) or smoking (OR 2.51, 95% CI 1.5–5.7) alone. Plasma 6-keto-PGF1α, a stable metabolite of PGI2, was lower in individuals with the PTGS2 GG genotype (p<0.05). Smoking could further lower plasma 6-keto-PGF1α concentrations in GG genotype carriers than non-smokers, especially in patients with CAD. Conclusions: The PTGS2 polymorphism and smoking were synergistically and significantly associated in Chinese Uighur patients with CAD.

A Novel Polymorphism of the CYP4A11 Gene is Associated With Coronary Artery Disease.

Background: CYP4A11 (cytochrome P450, family 4, subfamily A, polypeptide 11) converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), which plays a crucial role in the modulation of cardiovascular homeostasis. The aim of the present study was to assess the association between the human CYP4A11 gene and coronary artery disease (CAD). Methods: A total of 361 patients with CAD and 315 controls were genotyped for 4 single-nucleotide polymorphisms (SNPs) of the human CYP4A11 gene (rs9332978, rs4660980, rs3890011, and rs1126742). The data were assessed for 3 groups: total participants, men, and women via case–control studies. Results: For total participants and men, the distribution of SNP3 (rs3890011) genotypes showed a significant difference between CAD and control participants (P = .030 and P = .013, respectively), the distribution of the recessive model of SNP3 (GG vs CC + GC) was significantly higher in CAD patients than in control participants (P = .011 and P = .014, respectively), the significant difference was retained after adjustment for covariates (for total participants, 95% confidence interval [CI]: 1.137-2.423, P = .009; and for males, 95% CI: 1.173-3.013, P = .009). Conclusions: rs3890011 maybe a novel polymorphism of the CYP4A11 gene associated with CAD in a Han Chinese population.

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.

A novel polymorphism of the CYP2J2 gene is associated with coronary artery disease in Uygur population in China.

BACKGROUND Cytochrome P450 (CYP) 2J2 is expressed in the vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs). The EETs are potent endogenous vasodilators and inhibitors of vascular inflammation. The aim of the present study was to assess the association between the human CYP2J2 gene polymorphism and coronary artery disease (CAD) in a Han and Uygur population of China. METHODS We use two independent case-control studies: a Han population (206 CAD patients and 262 control subjects) and an Uygur population (336 CAD patients and 448 control subjects). All CAD patients and controls were genotyped for the same three single nucleotide polymorphisms (SNPs) (rs890293, rs11572223 and rs2280275) of CYP2J2 gene by a real-time PCR instrument. RESULTS In the Uygur population, for total, the distribution of SNP3 (rs2280275) genotypes showed a significant difference between CAD and control participants (P=0.048). For total and men, the distribution of SNP3 (rs2280275) alleles and the dominant model (CC vs CT+TT) showed a significant difference between CAD and control participants (for allele: P=0.014 and P=0.035, respectively; for dominant model: P=0.014 and P=0.034, respectively). The significant difference in dominant model was retained after adjustment for covariates (OR: 0.279, 95% confidence interval [CI]: 0.176-0.440, P=0.001; OR: 0.240, 95% CI: 0.128-0.457, P=0.001, respectively). CONCLUSIONS The CC genotype of rs2280275 in CYP2J2 gene could be a protective genetic marker of CAD and T allele may be a risk genetic marker of CAD in men of Uygur population in China.