Association of a genetic variant in the apolipoprotein A5 gene with the metabolic syndrome in Chinese.

OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 gene (APOA5) are associated with hypertriglyceridaemia in our population. We studied the associations of SNPs in APOA5 with the metabolic syndrome (MetS) in the Hong Kong and Guangzhou Chinese. METHODS: We genotyped five tagging SNPs in 1330 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort with follow-up after a median interval of 6·4 years; 1952 subjects from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Subcohort were used to replicate the findings. The MetS was defined according to the consensus criteria proposed jointly by several organizations in 2009. RESULTS: The SNP rs662799 (-1131T>C) was associated with the MetS (odds ratio = 1·47, P = 0·00082) and the number of its components present (regression coefficient = 0·204, P = 4·6 × 10(-5) ) after adjusting for age, sex, smoking, drinking and education in Hong Kong subjects at baseline. Similar association of this SNP was found in Hong Kong subjects at follow-up (P = 0·010 and 0·00021, respectively) and in Guangzhou subjects (P = 0·0041 and 0·017, respectively). The association of rs662799 with the number of the MetS components was significant regardless of age, sex, obesity and alcohol drinking, but almost disappeared after further adjusting for plasma triglycerides. CONCLUSION: Our results showed that the -1131T>C polymorphism in APOA5 was associated with the MetS because of its strong effect on plasma triglycerides. This may partly explain the higher cardiovascular risk in people with this polymorphism.

A single nucleotide polymorphism in APOA5 determines triglyceride levels in Hong Kong and Guangzhou Chinese.

Single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 (APOA5) gene have been associated with hypertriglyceridaemia. We investigated which SNPs in the APOA5 gene were associated with triglyceride levels in two independent Chinese populations. In all, 1375 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study were genotyped for five tagging SNPs chosen from HapMap. Replication was sought in 1996 subjects from the Guangzhou Biobank Cohort Study. Among the five SNPs, rs662799 (-1131T>C) was strongly related to log-transformed triglyceride levels among Hong Kong subjects (ß=0.192, P=2.6 × 10(-13)). Plasma triglyceride level was 36.1% higher in CC compared to TT genotype. This association was confirmed in Guangzhou subjects (ß=0.159, P=1.3 × 10(-12)), and was significantly irrespective of sex, age group, obesity, metabolic syndrome, hypertension, diabetes, smoking and alcohol drinking. The odds ratios and 95% confidence interval for plasma triglycerides ≥1.7 mmol/l associated with TC and CC genotypes were, respectively, 1.81 (1.37-2.39) and 2.22 (1.44-3.43) in Hong Kong and 1.27 (1.05-1.54) and 1.97 (1.42-2.73) in Guangzhou. Haplotype analysis suggested the association was due to rs662799 only. The corroborative findings in two independent populations indicate that the APOA5-1131T>C polymorphism is an important and clinically relevant determinant of plasma triglyceride levels in the Chinese population.

[Polymorphisms of vascular diseases-related genes in Guangzhou Biobank Cohort Study].

OBJECTIVE: To study the polymorphisms of cerebrovascular and cardiovascular disease genes using Taqman single nucleotide polymorphism (SNP) genotyping kits. METHODS: A total of 2000 subjects were recruited from the Guangzhou Biobank Cohort Study (GBCS), and 15 SNPs were detected using Taqman SNP genotyping kits and an ABI 7900HT real time PCR system. The data were tested for the Hardy-Weinberg equilibrium, and then compared with the data of the Chinese population from the International HapMap Project (HapMap_HCN). RESULTS: (1) All genotype data of the 15 SNPs were consistent with the Hardy-Weinberg rules. (2) The significant differences were observed among two SNPs, rs4220 and rs5368 and the HapMap_HCN (rs4220 28.2% vs 17.8%; chi(2) = 4.891, P = 0.028; rs5368 22.1% vs 32.2%, chi(2) = 5.137, P = 0.024). Comparing other gene bank data, such as AFD-CHN-PANEL, the Allele Frequency Database (ALFRED) and JBIC-allele, it would be most likely that our observations represent differences between the Northern and Southern populations in China. CONCLUSION: Such Biobank study provided a useful platform for the study of the role of genetic and environmental determinants on cerebrovascular and cardiovascular disease.

Interleukin-6 receptor gene polymorphism modulates interleukin-6 levels and the metabolic syndrome: GBCS-CVD.

Interleukin-6 (IL-6) is a key pleiotropic cytokine that modulates the inflammatory response. Single-nucleotide polymorphisms (SNPs) within associated genes may contribute to the metabolic syndrome (MES). We examined the role of the IL-6 (rs1524107-C/T) and IL-6 receptor (IL-6R, rs8192284-A/C, Asp358Ala) SNPs in modulating IL-6 levels and the syndrome. A total of 1,979 older Chinese subjects aged 50-92 years from Guangzhou Biobank Cohort Study (GBCS) were recruited. SNPs were detected using Taqman SNP genotyping kits. IL-6 was measured using enzyme-linked immunosorbent assay. The genotype frequencies were 4.9, 33.9, and 61.3% for the IL-6 CC, CT, and TT, and 12.0, 44.9, and 43.1% for the IL-6R CC, AC, and AA, respectively. Both SNPs were in Hardy-Weinberg equilibrium. The IL-6 SNP was not associated with IL-6 levels or the MES, but was dose-dependently associated with fibrinogen levels, P = 0.049. IL-6 levels significantly decreased with increasing proportions of the IL-6R A-allele 9.8 ± 4.9, 9.3 ± 4.8, and 8.4 ± 4.3, respectively, P = 0.001. Conversely, the A-allele was associated with elevated triglyceride, P = 0.009, C-reactive protein, P = 0.047, and potentially with fasting glucose levels, P = 0.077. There was an increasing prevalence of the MES in those carrying the IL-6R CC, AC, and AA genotypes at 18.1, 21.5, 25.2%, respectively, P = 0.010. The SNP was a significant independent predictor of the MES after adjusting for general obesity, age, gender and lifestyle, and socioeconomic parameters, P = 0.023. These data, which are in accord with studies from white populations suggest the IL-6R SNP may play a role in the pathogenesis of the MES possibly through modulating IL-6 levels.

Brachial-ankle pulse wave velocity and cardiovascular risk factors in the non-diabetic and newly diagnosed diabetic Chinese: Guangzhou Biobank Cohort Study-CVD.

BACKGROUND: Increased arterial stiffness is an important cause of cardiovascular disease (CVD). We examined determinants of arterial stiffness in subjects across strata of glycaemic status. METHODS: A total of 1249 subjects from a sub-study of the Guangzhou Biobank Cohort Study (GBCS-CVD) had brachial-ankle pulse wave velocity (baPWV) measured by automatic oscillometric method. Major cardiovascular risk factors including glycosylated haemoglobin A1c (HbA(1c)), high sensitivity C-reactive protein (hsCRP), fasting triglyceride, low- and high-density lipoprotein cholesterol and both fasting and post 2-h oral glucose-load glucose, systolic and diastolic blood pressure were assessed. RESULTS: In all, 649, 479 and 121 subjects were classified into normoglycaemia, impaired glucose metabolism (IGM) and newly diagnosed diabetes groups, respectively. Both age and systolic blood pressure were significantly associated with increased baPWV in all three groups (all p < 0.001). In both normoglycaemic and IGM groups, hsCRP and HbA(1c) were positively associated with baPWV (p from 0.04 to < 0.001), whereas current smoking and triglyceride were associated with baPWV in the normoglycaemic and IGM group, respectively (p = 0.04 and 0.001). No gender difference in baPWV was observed in the normoglycaemic or IGM groups. However, in the newly diagnosed diabetes group, men had higher baPWV than women (p = 0.01). CONCLUSIONS: In the normoglycaemic and IGM subjects, after adjusting for age, blood pressure and other confounders, increasing HbA(1c) was associated with increased baPWV, suggesting a pathophysiological role of chronic glycaemia that can contribute to vascular disease risk in persons without diabetes.

The metabolic syndrome is associated with subclinical atherosclerosis independent of insulin resistance: the Guangzhou Biobank Cohort Study-CVD.

OBJECTIVE: We examined whether the association of the metabolic syndrome (MetS) and subclinical atherosclerosis is independent of insulin resistance in a Chinese community sample with no history of type 2 diabetes. METHODS: Five hundred and ninety-six men and 526 women from a substudy of the Guangzhou Biobank Cohort Study (GBCS-CVD) had carotid intimal-medial thickness (IMT) measured by B-mode ultrasonography, and brachial-ankle pulse wave velocity (PWV) and ankle-brachial systolic blood pressure index (ABI) measured simultaneously by a noninvasive automatic waveform analyser. RESULTS: Fourteen percentage had MetS as defined by the International Diabetes Federation. Obesity indices, systolic and diastolic blood pressure and pulse pressure, lipids, fasting and postload glucose and insulin, homeostatic model assessment of insulin resistance, glycosylated haemoglobin A1c, leptin, high-sensitivity C-reactive protein, IMT and PWV increased and high-density lipoprotein-cholesterol, adiponectin and ABI decreased significantly with increasing number of MetS components after adjusting for age and sex (P for trend from 0.004 to <0.001). After adjusting for traditional cardiovascular risk factors and insulin resistance, the odds ratios [OR (95% CI)] of thicker IMT (> or =1.0 mm), higher PWV (> or =14.0 m/s) and low ABI (< or =1.0) for MetS were significantly increased [2.28 (1.19-4.38), 2.17 (1.36-3.46) and 1.72 (1.14-2.59), respectively, all P < 0.01] but were lower than the adjusted OR for those with three or more MetS components. CONCLUSION: MetS was associated with subclinical atherosclerosis independent of insulin resistance. The presence of increasing number of MetS risk factors appeared to be more important than the diagnosis of MetS in predicting subclinical atherosclerosis. Early screening for MetS risk factors might identify those at greater cardiovascular risk.

Impact of impaired fasting glucose and impaired glucose tolerance on arterial stiffness in an older Chinese population: the Guangzhou Biobank Cohort Study-CVD.

The aim of the study was to compare the impact of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) on vascular function among older Chinese people. A random sample of 671 men and 603 women aged 50 to 85 years without known diabetes from the Guangzhou Biobank Study-CVD was examined in a cross-sectional study. Subjects with no previously confirmed or treated diabetes but with both fasting plasma glucose less than 5.6 mmol/L and 2-hour glucose from 7.8 to less than 11.0 mmol/L were classified as having isolated IGT, and those with no previously confirmed and treated diabetes but with both fasting plasma glucose from 5.6 to less than 7.0 mmol/L and 2-hour glucose less than 7.8 mmol/L were classified as having isolated IFG. A total of 11.0% of the men and 8.6% of the women had isolated IFG, and 17.7% of the men and 18.6% of the women had isolated IGT. The brachial-ankle pulse wave velocity and pulse pressure were increased in both the isolated IFG and isolated IGT subjects compared with the normoglycemia group (both Ps < .001). Compared with subjects with isolated IFG, those with isolated IGT appeared to have a higher age- and sex-adjusted brachial-ankle pulse wave velocity (1543 +/- 22 vs 1566 +/- 17, P = .07) and to be more insulin resistant (2-hour postload insulin: 54.2 +/- 2.13 vs 26.8 +/- 2.99 muU/mL, P < .001), had a worse lipid profile (apolipoprotein [apo] B: 1.07 +/- 0.02 vs 0.97 +/- 0.02 g/L, P < .001; apo B/apo A-1 ratio: 0.80 +/- 0.02 vs 0.69 +/- 0.02, P < .001), but had lower glycosylated hemoglobin levels (6.03% +/- 0.06% vs 5.86% +/- 0.04%, P < .001) (values are mean +/- SE). Subjects with isolated IGT had greater arterial stiffness, probably as a result of being more insulin resistant, with a worse lipid profile than those with isolated IFG. The sole use of fasting glucose level to identify prediabetic people would fail to identify a significant proportion of the at-risk population.

[Effect of physical activity strength on the diabetes mellitus prevalence in the elderly under the influence of International Physical Activity Questionnaire].

OBJECTIVE: To examine the impact of International Physical Activity Questionnaire (IPAQ) physical activity intensity on to the prevalence of diabetes mellitus among Chinese elderly. METHODS: A total number of 1996 residents aged 50 or above living in Guangzhou city were recruited from the phase 3 of the Guangzhou Biobank Cohort Study. Information on physical activity and fasting plasma glucose status was derived from standardized interviews and laboratory assays. RESULTS: Among the participants who were classified as physically active (60.0%), moderate active (29.8%) and inactive (10.2%), the prevalence rates of type 2 diabetes mellitus were 9.1%, 12.0% and 14.2%, respectively. After adjustment on age, sex, obesity and other potential confounding factors, data from logistic regression model showed that the odds ratios (95% confidence interval) for diabetes on subjects in physically moderate active and active group were 0.75(0.46-1.26)and 0.60(0.38-0.97) respectively with P for trend as 0.03, when comparing to those physically inactive ones. CONCLUSION: Promotion of physical activity might have had some effects in reducing the risk of diabetes mellitus among the older adults.