Cross-sectional study of household solid fuel use and renal function in older adults in China.

BACKGROUND: Emerging evidence links outdoor air pollution and declined renal function but the relationship between household air pollution and renal function is not well understood. METHODS: Using cross-sectional data from the multi-provincial INTERMAP-China Prospective Study, we collected blood samples and questionnaire information on stove use and socio-demographic factors. We calculated estimated glomerular filtration rate (eGFR) from serum creatinine to assess renal function. Participants with eGFR <60 mL/min per 1.73 m2 were defined as having chronic kidney disease (CKD) in this analysis. Generalized estimating equations were used to estimate the association of household fuel with renal function and prevalent CKD in models adjusting for confounders. RESULTS: Among the 646 enrolled adults (40-79y; 56% female), one-third exclusively used clean fuel (gas and electric) cookstoves and 11% of northern China participants (n = 49 of 434) used only clean fuel heaters, whereas the rest used solid fuel. In multivariable models, use of solid fuel cookstoves was associated with 0.17 ml/min/1.73 m2 (95% CI: -0.30, 0.64) higher eGFR and 19% (0.86, 1.64) higher prevalence of CKD than exclusive clean fuel use. Greater intensity of solid fuel use was associated with 0.25 ml/min/1.73 m2 (-0.71, 0.21) lower eGFR per 5 stove-use years, though the confidence intervals included the null, while greater current intensity of indoor solid fuel use was associated with 1.02 (1.00, 1.04) higher prevalent CKD per 100 stove-use days per year. Larger associations between current solid fuel use and intensity of use with lower eGFR and prevalent CKD were observed among participants in southern China, those with hypertension or diabetes (eGFR only), and females (CKD only), through these groups had small sample sizes and some confidence intervals included the null. CONCLUSION: We found inconsistent evidence associating household solid fuel use and renal function in this cross-sectional study of peri-urban Chinese adults.

Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension.

Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant (P < 5.0 × 10(-8)) associations with blood pressure, which included variants at three new loci (CACNA1D, CYP21A2, and MED13L) and a newly discovered variant near SLC4A7. We also replicated 14 previously reported loci, 8 (CASZ1, MOV10, FGF5, CYP17A1, SOX6, ATP2B1, ALDH2, and JAG1) at genome-wide significance, and 6 (FIGN, ULK4, GUCY1A3, HFE, TBX3-TBX5, and TBX3) at a suggestive level of P = 1.81 × 10(-3) to 5.16 × 10(-8). These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.

Contemporary Epidemiology, Management, and Outcomes of Patients Hospitalized for Heart Failure in China: Results From the China Heart Failure (China-HF) Registry.

BACKGROUND: Contemporary data on the epidemiology of heart failure (HF) in China are scarce. The China-HF Registry was designed to investigate clinical characteristics, management, and outcomes of patients hospitalized for HF in China. METHODS AND RESULTS: Data were collected prospectively on 13,687 patients with a primary discharge diagnosis of HF who were enrolled from 132 participating hospitals from January 2012 to September 2015. Data from the China-HF Registry was compared with previously published literature. The mean age was 65 ± 15 years, 59.1% were male, and 36.0% had preserved ejection fraction. Age, body mass index, and systolic blood pressure were lower than in high-income countries. Common comorbidities included hypertension (50.9%), coronary heart disease (49.6%), and atrial fibrillation (24.4%). The overall use of diuretics, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB), and ß-blockers at admission was 30.1%, 27.0%, and 25.6%, respectively, which was lower than in other registries. For patients discharged alive, ACEI/ARB, ß-blocker, and mineralocorticoid receptor antagonist use in patients with reduced ejection fraction was 67.5%, 70.0%, and 74.1%, respectively; device use was much lower. The median length of hospital stay was 10 (range 7-15) days, and in-hospital mortality was 4.1 ± 0.3%. Predictors of mortality included low systolic blood pressure, acute myocardial infarction, infection, right bundle branch block, and elevated total bilirubin and blood urea nitrogen level. CONCLUSIONS: Several important findings in patient profile and treatment patterns among Chinese patients with HF were noted compared with published literature. These data underscore the need for regional characterization of HF for global clinical trials and for the identification of several quality improvement opportunities.

[Relationship between physical activity and the incidence of metabolic syndrome in Chinese adults: a prospective cohort study].

OBJECTIVE: To investigate the association between physical activity (PA) and the incidence of metabolic syndrome (MS) in Chinese adults. METHODS: Data on PA and other variables were obtained at the baseline examination of China Multi-center study of Cardiovascular Epidemiology in 1998 and of International Collaborative study of Cardiovascular Disease in Asia(InterASIA) during 2000 - 2001. Follow-up study was conducted in 2007 - 2008. A total of 11 512 Chinese adults aged 35 - 74 years (5563 men and 5949 women) were included in the final data analysis. Information on demographics, PA, smoking and alcohol consumption were obtained and components of MS were examined. Participants were divided into four groups according to quartile of total metabolic equivalent (MET) values per day. In addition, subjects were grouped into the following categories according to occupational PA: inactive, light, moderate and vigorous. Binary logistic model was used to examine the association between PA and the incidence of MS. RESULTS: A total of 2527 cases with MS were documented during an average following up of 8.1 years. The annual incidence rate of MS was 2.71% (2527/93 178.68). After multivariate logistic regression analysis, compared with participants with total PA volume < 32.0 MET×h×d(-1) (annual incidence rate was 3.19% (697/21 830.74)), the RR (95%CI) value of participants with total PA volume during 32.00 - 37.85, 37.86 - 52.29, and ≥ 52.30 MET×h×d(-1) was 1.05(0.92 - 1.19), 0.98(0.86 - 1.12), and 0.68(0.59 - 0.80), respectively (χ(2)trend = 34.23, P < 0.05), with corresponding annual incidence rates of 2.82% (690/24 504.25), 2.73% (661/24 179.36) and 2.11% (479/22 664.33). In addition, compared to inactive occupational PA (annual incidence rate was 2.76% (402/14 588.33)), the corresponding RR (95%CI) value was 0.80 (0.69 - 0.92), 0.70 (0.59 - 0.82), and 0.54 (0.45 - 0.65) (χ(2)trend = 42.34, P < 0.05), and the annual incidence rates were 2.86% (648/22 663.41), 2.40% (455/18 956.14) and 1.89% (344/18 173.86) in participants with light, moderate and vigorous occupational PA, respectively. CONCLUSION: Both increased total PA volume and occupational PA intensity are significantly associated with decreased risk of incidence of MS.

Household Air Pollution and Blood Pressure, Vascular Damage, and Subclinical Indicators of Cardiovascular Disease in Older Chinese Adults.

BACKGROUND: Limited data suggest that household air pollution from cooking and heating with solid fuel (i.e., coal and biomass) stoves may contribute to the development of hypertension and vascular damage. METHODS: Using mixed-effects regression models, we investigated the associations of household air pollution with blood pressure (BP) and vascular function in 753 adults (ages 40-79 years) from 3 diverse provinces in China. We conducted repeated measures of participants' household fuel use, personal exposure to fine particulate air pollution (PM2.5), BP, brachial-femoral pulse wave velocity (bfPWV), and augmentation index. Ultrasound images of the carotid arteries were obtained to assess intima-media thickness (CIMT) and plaques. Covariate information on sociodemographics, health behaviors, 24-h urinary sodium, and blood lipids was also obtained. RESULTS: Average estimated yearly personal exposure to PM2.5 was 97.5 µg/m3 (SD: 79.2; range: 3.5-1241), and 65% of participants cooked with solid fuel. In multivariable models, current solid fuel use was associated with higher systolic (2.4 mm Hg, 95% CI: -0.4, 4.9) and diastolic BP (1.4 mm Hg, 95% CI: -0.1, 3.0) and greater total area of plaques (1.7 mm2, 95% CI: -6.5, 9.8) compared with exclusive use of electricity or gas stoves. A 1 - ln(µg/m3) increase in PM2.5 exposure was associated with higher systolic (1.5 mm Hg, 95% CI: 0.2, 2.7) and diastolic BP (1.0 mm Hg, 95% CI: 0.4, 1.7) and with greater CIMT (0.02 mm, 95% CI: 0.00, 0.04) and total area of plaques (4.7 mm2, 95% CI: -2.0, 11.5). We did not find associations with arterial stiffness, except for a lower bfPWV (-1.5 m/s, 95% CI: -3.0, -0.0) among users of solid fuel heaters. CONCLUSIONS: These findings add to limited evidence that household air pollution is associated with higher BP and with greater CIMT and total plaque area.

Central rather than brachial pressures are stronger predictors of cardiovascular outcomes: A longitudinal prospective study in a Chinese population.

The purpose of this study was to assess the association of blood pressure (BP) measurements with the risk of cardiovascular disease (CVD) and examine whether central systolic BP (CSBP) predicts CVD better than brachial BP measurements (SBP and pulse pressure [PP]). Based on a cross-sectional study conducted in 2009-2010 with follow-up in 2016-2017 among 35- to 64-year-old subjects in China, we evaluated the performance of non-invasively predicted CSBP over brachial BP measurements on the first CVD events. Each BP measurement, individually and jointly with another BP measurement, was entered into the multivariate Cox proportional-hazards models, to examine the predictability of central and brachial BP measurements. Mean age of participants (n = 8710) was 50.1 years at baseline. After a median follow-up of 6.36 years, 187 CVD events occurred. CSBP was a stronger predictor for CVD than brachial BP measurements (CSBP, 1-standard deviation increment HR = 1.49, 95%CI: 1.31-1.70). With CSBP and SBP entering into models jointly, the HR for CSBP and SBP was 1.28 (1.04-1.58) and 1.22 (0.98-1.50), respectively. With CSBP and PP entering into models jointly, the HR for CSBP and PP was 1.51 (1.28-1.78) and 0.98 (0.83-1.15), respectively. For subgroup analysis, the association of CSBP with CVD was stronger than brachial BP measurements in women, those with hypertension and obesity. In the middle-aged Chinese population, noninvasively estimated CSBP may offer advantages over brachial BP measurements to predict CVD events, especially for participants with higher risk. These findings suggest prospective assessment of CSBP as a prevention and treatment target in further trials.

The impact of severity of hypertension on association of PGC-1alpha gene with blood pressure and risk of hypertension.

BACKGROUND: Little is known about the impact of severity of hypertension on the association of genes with high blood pressure, which may cause the inconsistently reported associations of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) gene with blood pressure. METHODS: A cardiovascular epidemiology survey and genotyping were performed in a population-based sample of 1642 apparently healthy residents (648 men and 994 women aged 35-91 years). RESULTS: After adjusting for age, sex, body mass index, and antihypertensive medication, G482S and +2962A/G polymorphisms were significantly associated with systolic blood pressures in hypertension patients with medication use (p = 0.023 and 0.022 for G482S and +2962A/G respectively) but not in all participants, normotensives, and patients with no medication use. Multivariable logistic models showed that the two polymorphisms were significantly associated with severe hypertension (SBP > or = 160 mm Hg or DBP > or = 100 mm Hg regardless of medication use), with an OR of 0.6(95% confidence interval [CI]: 0.4-0.98) for S482S vs. G482G and an OR of 1.9(95% CI: 1.2-3.0) for +2962G/G vs. +2962A/A, but not with regular hypertension (SBP > or = 140 mm Hg or DBP > or = 90 mm Hg or current use of antihypertensive medications), with an OR of 0.9(95% CI: 0.7-1.2) for S482S vs. G482G and an OR of 0.9(95% CI: 0.7-1.4) for +2962G/G vs. +2962A/A. Haplotype combination analyses showed a significant synthetic effect (OR of severe hypertension for persons with G482X and +2962G/G = 2.6, 95%CI: 1.5-4.4, with reference to persons with S482S and +2962A/X). CONCLUSION: In this study, we found that G482S and +2962A/G polymorphisms of PGC-1alpha gene were only significantly associated with severe hypertension defined by occasional clinic blood pressure measurements. This finding suggested severe hypertension rather than regular hypertension should be used as the outcome in studies on association of genes with blood pressure or hypertension, in order to have a better power.

Incidence of type 2 diabetes and number of events attributable to abdominal obesity in China: A cohort study.

BACKGROUND: The aim of the present study was to estimate the incidence of type 2 diabetes (T2D) and the number of diabetes events attributable to abdominal obesity in China. METHODS: A cohort study was conducted in a sample of 24,996 Chinese adults aged 35-74 years, with 19.9% of subjects lost to follow-up. Waist circumference (WC) was measured at baseline in 1998 and 2000-01, and abdominal obesity was defined as WC ≥ 90 cm in men and ≥80 cm in women. Information on incident diabetes was collected during follow-up in 2007-08. We estimated the number of T2D events attributed to abdominal obesity using confounder-adjusted population-attributable risk, incidence of diabetes, and the population size of China in 2010. RESULTS: After a mean follow-up of 8.0 years, the age-standardized incidence of T2D was 9.6 and 9.2 per 1000 person-years in men and women, respectively. Abdominal obesity accounted for 28.1% (95% confidence interval [CI] 14.8%, 40.5%) of incident diabetes among men and 41.2% (95% CI 28.3%, 52.6%) among women using the diagnostic criteria of abdominal obesity recommended by the International Diabetes Federation. We estimated that, in 2010, 2.4 (95% CI 1.5, 3.2) million diabetes events were attributable to abdominal obesity: 1.0 (95% CI 0.5, 1.4) million in men and 1.4 (95% CI 1.0, 1.8) million in women. CONCLUSIONS: Abdominal obesity is a major risk factor for T2D. Strengthening programs and initiatives for preventing and controlling obesity focusing on lifestyle changes should be a priority in the national strategy to reduce diabetes burden in China.

Genetic Susceptibility to Lipid Levels and Lipid Change Over Time and Risk of Incident Hyperlipidemia in Chinese Populations.

BACKGROUND: Multiple genetic loci associated with lipid levels have been identified predominantly in Europeans, and the issue of to what extent these genetic loci can predict blood lipid levels increases over time and the incidence of future hyperlipidemia remains largely unknown. METHODS AND RESULTS: We conducted a meta-analysis of genome-wide association studies of lipid levels in 8344 subjects followed by replication studies including 14 739 additional individuals. We replicated 17 previously reported loci. We also newly identified 3 Chinese-specific variants in previous regions (HLA-C, LIPG, and LDLR) with genome-wide significance. Almost all the variants contributed to lipid levels change and incident hyperlipidemia >8.1-year follow-up among 6428 individuals of a prospective cohort study. The strongest associations for lipid levels change were detected at LPL, TRIB1, APOA1-C3-A4-A5, LIPC, CETP, and LDLR (P range from 4.84×10(-4) to 4.62×10(-18)), whereas LPL, TRIB1, ABCA1, APOA1-C3-A4-A5, CETP, and APOE displayed significant strongest associations for incident hyperlipidemia (P range from 1.20×10(-3) to 4.67×10(-16)). The 4 lipids genetic risk scores were independently associated with linear increases in their corresponding lipid levels and risk of incident hyperlipidemia. A C-statistics analysis showed significant improvement in the prediction of incident hyperlipidemia on top of traditional risk factors including the baseline lipid levels. CONCLUSIONS: These findings identified some evidence for allelic heterogeneity in Chinese when compared with Europeans in relation to lipid associations. The individual variants and those cumulative effects were independent risk factors for lipids increase and incident hyperlipidemia.

Type 2 diabetes mellitus incidence in Chinese: contributions of overweight and obesity.

AIMS: To estimate the incidence of Type 2 diabetes mellitus (T2DM) and the number of those with T2DM attributable to overweight and obesity in China. METHODS: We conducted a prospective cohort study among 15680 participants (46.4%, men) aged 35-74 years. The mean duration of follow-up was 8.0 years. We examined the relationship between overweight, obesity and risk of T2DM by Cox proportional hazards models. Population attributable risk (PAR) of overweight and obesity was also calculated. Moreover, we estimated the number of T2DM events attributed to overweight and obesity using PAR, incidence of T2DM and the population size of China in 2010. RESULTS: During a mean follow-up of 8.0 years, the age-standardized incidence of T2DM was 9.5 per 1000 person-years in men and 9.2 in women. Overweight accounted for 28.3% (95% confidence interval [CI]: 20.1, 36.2) of incident T2DM among men and 31.3% (95% CI: 25.5, 36.9) among women. The corresponding PAR of obesity was 10.1% (95% CI: 6.0, 14.2) among men and 16.8% (95% CI: 12.0, 21.6) among women. Approximately 3.32 million (95% CI: 2.47, 4.24) incident T2DM were attributable to overweight and obesity in Chinese adults who were 35 to 74 years in 2010. CONCLUSION: Our results indicate that incident T2DM is mainly attributable to overweight and obesity in China. It is extremely important to advocate healthy lifestyle and prevent excessive weight gain for reducing T2DM burden in China.

Physical activity level and incident type 2 diabetes among Chinese adults.

PURPOSE: The objective is to examine the association between physical activity level (PAL) and incident type 2 diabetes among middle-age and older Chinese men and women in urban China. METHODS: This prospective study included 6348 participants (age 35 to 74 yr) who were free of diabetes and cardiovascular disease at baseline. PAL was estimated on the basis of self-reported overall physical activity on a typical day. According to PAL, participants were classified into four groups: sedentary (PAL, 1.00-1.39), low active (PAL, 1.40-1.59), active (PAL, 1.60-1.89), and very active (PAL, >1.89). The association of PAL with incident diabetes was examined by Cox proportional hazards model. RESULTS: During 7.9 yr of follow-up (50,293 person-years), 478 incident cases of type 2 diabetes were identified. After adjustment for age, sex, geographic region, educational level, smoking, alcohol use, and family history of diabetes, the HR (95% CI) values for type 2 diabetes across increasing categories of PAL were 1.00 (reference), 0.82 (0.62-1.09), 0.63 (0.47-0.83), and 0.47 (0.36-0.61), respectively (P for trend <0.0001). Additional adjustment for baseline body mass index or waist circumference attenuated the magnitude of risk reduction, but it remained significant. The inverse association between PAL and risk of incident diabetes was persistent in subgroup analyses according to age, sex, hypertension, smoking, body mass index, waist circumference, and fasting plasma glucose level. CONCLUSIONS: Higher PAL is associated with substantial reduction in risk of type 2 diabetes. Our findings suggest the importance of a physically active lifestyle in the prevention of diabetes.

Genetic predisposition to higher blood pressure increases risk of incident hypertension and cardiovascular diseases in Chinese.

Although multiple genetic markers associated with blood pressure have been identified by genome-wide association studies, their aggregate effect on risk of incident hypertension and cardiovascular disease is uncertain, particularly among East Asian who may have different genetic and environmental exposures from Europeans. We aimed to examine the association between genetic predisposition to higher blood pressure and risk of incident hypertension and cardiovascular disease in 26 262 individuals in 2 Chinese population-based prospective cohorts. A genetic risk score was calculated based on 22 established variants for blood pressure in East Asian. We found the genetic risk score was significantly and independently associated with linear increases in blood pressure and risk of incident hypertension and cardiovascular disease (P range from 4.57×10(-3) to 3.10×10(-6)). In analyses adjusted for traditional risk factors including blood pressure, individuals carrying most blood pressure-related risk alleles (top quintile of genetic score distribution) had 40% (95% confidence interval, 18-66) and 26% (6-45) increased risk for incident hypertension and cardiovascular disease, respectively, when compared with individuals in the bottom quintile. The genetic risk score also significantly improved discrimination for incident hypertension and cardiovascular disease and led to modest improvements in risk reclassification for cardiovascular disease (all the P<0.05). Our data indicate that genetic predisposition to higher blood pressure is an independent risk factor for blood pressure increase and incident hypertension and cardiovascular disease and provides modest incremental information to cardiovascular disease risk prediction. The potential clinical use of this panel of blood pressure-associated polymorphisms remains to be determined.

[Incidence of obesity and its modifiable risk factors in Chinese adults aged 35-74 years: a prospective cohort study].

OBJECTIVE: To examine the incidence of obesity and its modifiable risk factors in Chinese adults aged 35-74 years. METHODS: A total of 27 020 participants aged 35 to 74 years from two prospective cohort studies in China were followed up in the years of 2007 and 2008. Obesity and overweight were defined as body mass index ≥ 28.0, and 24.0-27.9 kg/m(2), respectively. Relative risks of obesity for risk factors were computed by using logistic regression. RESULTS: The annual incidence rates of obesity and overweight were 6.97 ‰ and 24.83 ‰ in Chinese adults aged 35-74 years, respectively. Women had a higher incidence of obesity than men (7.74 ‰ vs. 6.10 ‰). Participants in northern China had a higher incidence than those in southern (9.29 ‰ vs. 5.10 ‰) part of the country. Adults in rural had a higher incidence than those in urban (7.28 ‰ vs. 6.52 ‰). After adjusting for the baseline variables, such as gender, age, geographic region, degree of urbanization, the relative risk for obesity was 0.82 (95% CI:0.68-0.99) for participants with ≥ 12 years' education, compared with those <12 years. Participants with middle income, less physical activity at work/housework or being retirees, consuming more red meat and scented tea etc, had higher risk of incidence of obesity. Participants who consumed milk and moderate amount of fruits, would show a lower risk of obesity. CONCLUSION: The incidence of obesity was 6.97 ‰ in Chinese middle and older adults. Our results underscored that the promotion of healthy lifestyle which include issues as increasing physical activity, consuming moderate amount of fruits and milk but less red meat, drinking less scented tea etc, could play key roles in obesity prevention and control among the Chinese adults, especially among people with low education level or with middle income.

Blood pressure responses to dietary sodium and potassium interventions and the cold pressor test: the GenSalt replication study in rural North China.

BACKGROUND: In the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study, we observed that blood pressure (BP) responses to dietary sodium and potassium interventions and the cold pressor test (CPT) varied greatly among individuals. We conducted a replication study to confirm our previous findings among 695 study participants. METHODS: The dietary intervention included a 7-day low sodium (51.3 mmol/day), a 7-day high sodium (307.8 mmol/day), and a 7-day high sodium with potassium supplementation (307.8 mmol sodium and 60 mmol potassium/day). BP measurements were obtained during the baseline and each intervention phase. During the CPT, BP was measured before and at 0, 1, 2, and 4 minutes after the participants immersed their right hand in ice water for 1 minute. RESULTS: Systolic and diastolic BP responses (mean ± SD (range), mm Hg) were 8.1±8.4 (-39.1 to 18.2) and -3.5±5.1 (-25.1 to 11.1) to low sodium, 9.1±8.4 (-13.3 to 33.1) and 4.0±5.4 (-16.0 to 20.7) to high sodium, and -4.6±5.8 (-31.8 to 11.6) and -1.9±4.3 (-16.9 to 14.2) to potassium supplementation, respectively (all P < 0.0001 for comparison with each former phase). The mean maximum systolic and diastolic BP responses to the CPT were 16.5±10.5 (-15.3 to 63.3) and 7.6±6.1 (-8.7 to 39.3), respectively (all P < 0.0001). CONCLUSIONS: Our study indicates that there are large variations in BP responses to dietary sodium and potassium interventions and to the CPT among individuals.

Common variants at 12q24 are associated with drinking behavior in Han Chinese.

BACKGROUND: Alcohol consumption is heritable, but genetic susceptibility to drinking behavior has not been investigated widely in genome-wide association studies. OBJECTIVE: We aimed to identify susceptibility loci for drinking behavior (drinkers compared with nondrinkers) in Han Chinese. DESIGN: We performed 2 genome-wide association studies including 1420 drinkers and 3590 nondrinkers in discovery, followed by a de novo replication analysis comprising 4896 drinkers and 13,293 nondrinkers. DNA samples of the subjects were collected for genotyping. RESULTS: The association results of drinking behavior (drinkers or nondrinkers) showed a cluster of single nucleotide polymorphisms at 12q24 in discovery (P < 5 × 10(-8)), with the strongest association for rs11066280 near C12orf51 (P-combined = 3.26 × 10(-215)). Moreover, we observed the association with drinking behavior for a functional variant in ALDH2 at 12q24 (rs671, P-discovery = 5.17 × 10(-35)). We also identified the association between rs11066280 and daily alcohol intake among drinkers (P-combined = 4.01 × 10(-21)). CONCLUSION: Our data indicate that common variants at 12q24 may contribute to the susceptibility of drinking behavior in Han Chinese.

Genome-wide association study identifies 8 novel loci associated with blood pressure responses to interventions in Han Chinese.

BACKGROUND: Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals' BP responses to dietary intervention and cold pressor test. METHODS AND RESULTS: We conducted a genome-wide association study of BP responses in 1881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/d), a 7-day high-sodium (307.8 mmol/d), and a 7-day high-sodium plus potassium supplementation (60 mmol/d). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified 8 novel loci for BP phenotypes, which physically mapped in or near PRMT6 (P=7.29 × 10(-9)), CDCA7 (P=3.57 × 10(-8)), PIBF1 (P=1.78 × 10(-9)), ARL4C (P=1.86 × 10(-8)), IRAK1BP1 (P=1.44 × 10(-10)), SALL1 (P=7.01 × 10(-13)), TRPM8 (P=2.68 × 10(-8)), and FBXL13 (P=3.74 × 10(-9)). There was a strong dose-response relationship between the number of risk alleles of these independent single-nucleotide polymorphisms and the risk of developing hypertension during the 7.5-year follow-up in the study participants. Compared with those in the lowest quartile of risk alleles, odds ratios (95% confidence intervals) for those in the second, third, and fourth quartiles were 1.39 (0.97, 1.99), 1.72 (1.19, 2.47), and 1.84 (1.29, 2.62), respectively (P=0.0003 for trend). CONCLUSIONS: Our study identified 8 novel loci for BP responses to dietary sodium and potassium intervention and cold pressor test. The effect size of these novel loci on BP phenotypes is much larger than those reported by the previously published studies. Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline.

Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease.

We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases and 5,019 controls followed by replication studies in 15,460 cases and 11,472 controls, all of Chinese Han ancestry. We identify four new loci for coronary artery disease that reached the threshold of genome-wide significance (P < 5 × 10(-8)). These loci mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (in or near PHACTR1, TCF21, CDKN2A-CDKN2B and C12orf51). These findings provide new insights into pathways contributing to the susceptibility for coronary artery disease in the Chinese Han population.

Association of monosodium glutamate intake with overweight in Chinese adults: the INTERMAP Study.

Animal studies indicate that monosodium glutamate (MSG) can induce hypothalamic lesions and leptin resistance, possibly influencing energy balance, leading to overweight. This study examines the association between MSG intake and overweight in humans. We conducted a cross-sectional study involving 752 healthy Chinese (48.7% women), aged 40-59 years, randomly sampled from three rural villages in north and south China. The great majority of participants prepared their foods at home, without use of commercially processed foods. Diet was assessed with four in-depth multipass 24-h recalls. Participants were asked to demonstrate MSG amounts added in food preparation. Amounts shaken out were weighed by trained interviewers. Overweight was defined as BMI > or =25.0 or > or =23.0 kg/m(2)(based on World Health Organization recommendations for Asian populations). Eighty-two percent of participants were MSG users. Average intake was 0.33 g/day (s.d. = 0.40). With adjustment for potential confounders including physical activity and total energy intake, MSG intake was positively related to BMI. Prevalence of overweight was significantly higher in MSG users than nonusers. For users in the highest tertile of MSG intake compared to nonusers, the multivariable-adjusted odds ratios of overweight (BMI > or =23.0 and > or =25.0) were 2.10 (95% confidence interval, 1.13-3.90, P for trend across four MSG categories = 0.03) and 2.75 (95% confidence interval, 1.28-5.95, P = 0.04). This research provides data that MSG intake may be associated with increased risk of overweight independent of physical activity and total energy intake in humans.

[Study on the relationship between Gln223arg variant in leptin receptor gene and obesity].

OBJECTIVE: To investigate the association between Gln223Arg variant in leptin receptor (LEPR) gene and obesity. METHODS: The subjects were from Yu county, Shanxi province, China. Data on cardiovascular risk factors was collected with questionnaire and their Gln223Arg variants in LEPR gene were genotyped. The relation between Gln223Arg variant in LEPR and obesity was analyzed. RESULTS: The genotype frequencies of G. G, G. A and AA were 0.7679, 0.2171 and 0.015 respectively and the allele frequencies of G and A were 0.8764 and 0.1236. The distribution of genotype was in Hardy-Weinberg equilibrium (P = 0.934). The results of single factor analysis showed that the carriers with the Arg223 alleles had higher weight (63.2 kg vs. 61.9 kg; P= 0.0307) and body mass index (24.4 kg/rn vs. 24.1 kg/m2; P = 0.0898) than those noncarriers of these alleles. Results from multivariate analysis indicated that the carriers with the Arg223 alleles had higher body mass index (24.5 kg/m2 vs. 24.1 kg/m ;P= 0.0396) and prevalence of obesity (OR = 1.30, 95% CI: 0.957-1.767; P= 0.0935). CONCLUSION: These data indicated that Gln223Arg variant in LEPR gene was possibly associated with obesity, respectively.

Blood pressure differences between northern and southern Chinese: role of dietary factors: the International Study on Macronutrients and Blood Pressure.

Blood pressure and prevalence of high blood pressure are greater for northern than southern Chinese. Reasons for these differences are unclear. Relationships of north-south blood pressure differences with multiple dietary factors were investigated in 839 Chinese participants, International Study on Macronutrients and Blood Pressure (INTERMAP), 561 northern, 278 southern, aged 40 to 59 years. Daily nutrient intakes were determined from four 24-hour dietary recalls and 2 timed 24-hour urine collections. Average systolic/diastolic pressure levels were 7.4/6.9 mm Hg higher for northern than southern participants. Southern participants had lower body mass index, sodium intake, sodium/potassium ratio, and higher intake of calcium, magnesium, phosphorus, and vitamins A and C. Considered singly, with control for age and gender, several dietary variables (eg, body mass index, urinary sodium/potassium ratio, urinary sodium, dietary phosphorus, and magnesium) reduced north-south blood pressure differences by > or =10%. Controlled for age and gender, nondietary variables had little effect on north-south blood pressure differences. With inclusion in regression models of multiple dietary variables (sodium, potassium, magnesium or phosphorus, body mass index), north-south blood pressure differences became much smaller (systolic -1.1, diastolic 1.6 mm Hg) and statistically nonsignificant. In conclusion, multiple dietary factors accounted importantly for north-south blood pressure differences. Efforts are needed to improve nutrition in China, especially in the north, as well as in other populations including those in the United States, for prevention and control of adverse blood pressure levels and major adult cardiovascular disease.