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Perchlorate and chlorate are ubiquitous pollutants that can adversely affect the thyroid function in humans. This study assessed the potential health risks associated with the dietary exposure of infants and young children to perchlorate and chlorate present in infant formulas available in Shanghai. The assessment was based on risk monitoring data from 150 samples of infant formulas in Shanghai between 2020 and 2022, along with the dietary consumption data of infants and young children. The detection rates of perchlorate and chlorate in infant formulas were 46.0% and 98.7%, with mean contents of 9.98 µg/kg and 112.01 µg/kg, and the maximum values of 151.00 µg/kg and 1475.00 µg/kg, respectively. The mean and 95th percentile (P 95) values of daily perchlorate exposure of 0-36-month-old infant and young children via infant formulas were 0.07 and 0.17 µg/kg body weight (bw) per day, respectively, which were lower than the tolerable daily intake (TDI) of perchlorate (0.3 µg/kg bw per day). The mean and P 95 values of chlorate exposure via infant formulas in 0-36-month-old infants and young children were 0.83 and 1.89 µg/kg bw per day, which were lower than the TDI of chlorate (3 µg/kg bw per day). The P 95 exposure of different age groups (0-6 months, 7-12 months and 13-36 months) of infants and young children to perchlorate and chlorate in infant formulas was below the TDI. Therefore, the risk associated with the exposure of 0-36-month-old infants and young children to perchlorate and chlorate from infant formulas in Shanghai is considered acceptable. Prioritizing environmental pollution control efforts to reduce the levels of perchlorate and chlorate in food products is important to safeguard the health of the infants and children under the One Health concept.
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Beer is susceptible to mycotoxin contamination originating from infected grains. It could be that mycotoxins are not completely removed during the brewing process and remain in the final product. Nevertheless, there have been no surveys of exposure to mycotoxin for Chinese inhabitants through beer consumption. This study aimed to investigate the presence of eight mycotoxins in 158 beer samples purchased in Shanghai, the largest megacity in China. The multiple mycotoxins determination was carried out using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Our findings revealed that 48.1% (76/158) of the beer samples were contaminated with Fusarium toxins. Deoxynivalenol-3-glucoside (D3G) and zearalenone (ZEN) were detected in 34.81% and 16.46% of the total samples, respectively. The significant differences between D3G/ZEN contamination and various beer types were performed. Furthermore, this study performed a health risk assessment for Shanghai residents based on data for Fusarium toxins and ochratoxin A (OTA) present in beer for the first time. The results revealed that the 95th percentile dietary exposures of Shanghai residents did not pose any chronic or acute health risks, either individually or in combination. Dietary exposures to Fusarium toxins revealed different risk levels among residents. The cumulative health risk for women is higher than that for men at the same beer consumption. In addition, the acute risk of DONs exposure for adults deserves concern. The insights obtained from this study may be of assistance for beer manufacturers and governmental regulators to further develop beer monitoring and guarantee public health.
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Bottlebrush polymers exhibiting unique properties have attracted considerable attention for applications in many research areas. Herein, the first simultaneous synthesis and self-assembly of bottlebrush block copolymers at room temperature via photoinitiated polymerization-induced self-assembly (photo-PISA) using multifunctional macromolecular chain transfer agents (macro-CTAs) is reported. Comparing with linear block copolymers, the bottlebrush block copolymers can promote the formation of higher-order morphologies (e.g., vesicles) when targeting similar degrees of polymerization (DPs). Moreover, a higher polymerization rate is observed in the case of bottlebrush block copolymers. Gel permeation chromatography (GPC) analysis shows that good polymerization control is maintained when synthesizing bottlebrush block copolymers by photo-PISA. Finally, the obtained bottlebrush block copolymer vesicles are used as seeds for further chain extension and multicompartment nanoparticles with a sponge internal structure are formed. It is expected that this study will not only expand polymer architectures employed in PISA, but also provide a new strategy to synthesize polymer nanoparticles with unique structures.
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Nanopartículas , Polímeros , Sustancias Macromoleculares , Nanopartículas/química , Polimerizacion , Polímeros/química , TemperaturaRESUMEN
A dietary survey of 3431 residents was conducted by a 24-h dietary recall method in Shanghai, China, quarterly from September 2013 to September 2014. A total of 400 food samples were tested for aluminium concentration, including wheat flour and puffed products from 2011 to 2013. Probabilistic analysis was used to estimate the dietary exposure to aluminium from wheat and puffed products. The means of dietary aluminium exposure for children (2-6 years old), juveniles (7-17 years old), adults (18-65 years old) and seniors (over 65 years old) were 1.88, 0.94, 0.44 and 0.42 mg kg(-1) body weight (bw) week(-1) respectively, with a population average of 0.51 mg kg(-1) bw week(-1). The proportions of those who had aluminium exposure from wheat and puffed products lower than the provisional tolerable weekly intake (PTWI) were 77%, 90%, 97%, and 97% respectively from children to seniors. We estimated that the proportions of people at risk would decrease by 13%, 6%, 2% and 2% respectively under the new China National Standards - GB 2760-2014 National Food Safety for Standards for using food additives. The results indicated that aluminium from wheat flour and puffed products is unlikely to cause adverse health effects in the general population in Shanghai; however, children were at a higher risk of excess aluminium exposure. Significant improvements in reducing the dietary exposure to aluminium are expected in the population, especially for children after the implementation of GB 2760-2014.
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Exposición a Riesgos Ambientales/análisis , Harina/análisis , Aditivos Alimentarios/análisis , Concentración Máxima Admisible , Modelos Estadísticos , Adolescente , Adulto , Anciano , Aluminio/análisis , Niño , Preescolar , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo/legislación & jurisprudencia , Triticum/químicaRESUMEN
In this study we propose a chromogenic platform for rapid analysis of organophosphate (OP) and carbamate (CM) insecticide residues, based on recombinant Drosophila melanogaster acetylcholinesterase (R-DmAChE) as enzyme and indoxyl acetate as substrate. The visible chromogenic strip had the advantages identical to those of commonly used lateral flow assays (LFAs) with utmost simplicity in sample loading and result observation. After optimization, depending on the color intensity (CI) values, the well-established assay has the capabilities of both qualitative measurement via naked eyes and quantitative analysis by colorimetric reader with the desirable IC(50) values against the tested six insecticides (0.06 µg mL(-1) of carbofuran, 0.28 µg mL(-1) of methomyl, 0.03 µg mL(-1) of dichlorvos, 31.6 µg mL(-1) of methamidophos, 2.0 µg mL(-1) of monocrotophos, 6.3 µg mL(-1) of omethoate). Acceptable matrix effects and satisfactory detection performance were confirmed by in-parallel LC-MS/MS analysis in different vegetable varieties at various spiked levels of 10(-3) to 10(1) µg g(-1). Overall, the testified suitability and applicability of this novel platform meet the requirements for practical use in food safety management and environmental monitoring, especially in the developing world.
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Acetilcolinesterasa/metabolismo , Carbamatos/análisis , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/enzimología , Insecticidas/análisis , Compuestos Organofosforados/análisis , Acetilcolinesterasa/genética , Animales , Colorimetría , Proteínas de Drosophila/genética , Indoles/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidad por Sustrato , Verduras/químicaRESUMEN
OBJECTIVE: To estimate the exposure of fluoride to pork and offal products of pigs and assess their health risks in Shanghai residents. METHODS: Conducting a dietary survey in 1630 residents cluster sampled from four districts in Shanghai. Detecting fluoride in 872 pork and offal samples, and using Monte Carlo method to estimate the chronic daily intake (CDI) and hazard quotient (HQ) of fluoride in Shanghai residents caused by eating pork and offal products of pigs. RESULT: The CDI of fluoride is less than the tolerable daily intake (TDI), and the HQ is less than 1. The intake of pork and offal product is less in elder people than young people (P < 0.05), and that is less in female than male (P < 0.05). The fluoride content in offal is higher than that in pork (P < 0.05), the fluoride in kidney (P < 0.05) and liver (P < 0.05) is higher than that in other viscera. CONCLUSION: The intake of fluoride from pork and offal products in Shanghai residents is lower than the TDI of fluoride and not reaching the risk level of fluoride causing dental fluorosis, unhealthy of bone and osteofluorosis.
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Dieta , Exposición a Riesgos Ambientales/efectos adversos , Fluoruros/administración & dosificación , Fluoruros/análisis , Carne/análisis , Adolescente , Adulto , Anciano , Animales , Niño , Preescolar , China , Encuestas sobre Dietas , Femenino , Fluoruros/efectos adversos , Análisis de los Alimentos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Medición de Riesgo , Encuestas y Cuestionarios , Porcinos , Adulto JovenRESUMEN
INTRODUCTION: Many studies demonstrated that a prolonged heart rate-corrected QT interval (QTc) increases the risk of malignant ventricular arrhythmias and sudden death. METHODS: We measured the electrocardiogram and blood pressure of 1480 hypertensive patients and assessed the relationship between the length of QTc and blood pressure. RESULTS: The mean QTc is longer in female than in male participants. There was a positive association between QTc and blood pressure in both men and women. The estimated increase in systolic and diastolic blood pressure for each 100-millisecond increase in QTc was 6.4 and 5.0 mm Hg in men and 3.7 and 2.5 mm Hg in women, respectively. CONCLUSION: Our study demonstrated a significant positive relationship between the QTc interval and baseline blood pressure in a Chinese hypertensive population.
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Hipertensión/fisiopatología , Síndrome de QT Prolongado/fisiopatología , Adulto , Anciano , Distribución de Chi-Cuadrado , China , Electrocardiografía , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Encuestas y CuestionariosRESUMEN
Our recent study indicated that MTHFR C677T polymorphism may involve in genetic control of blood pressure response to treatment by benazepril, an ACE inhibitor. Currently, we proposed to further investigate whether short-term blood pressure response to benazepril, was modulated by haplotypes re-constructed from both C677T and A1298C polymorphisms in MTHFR gene. A total of 410 hypertensive patients recruited from 344 nuclear families were treated orally with benazepril at a daily dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. In addition, 689 family members of these patients were also genotyped. Among these patients, the frequency of MTHFR A1298C AA, AC and CC genotypes was 74.4%, 23.9%, and 1.7%, respectively. The frequency of MTHFR C677T CC, CT and TT genotypes was 23.7%, 51.2%, and 25.1%, respectively. Only three haplotypes, 677T-1298A (50.8%), 677C-1298A (35.7%), and 677C-1298C (13.5%) were re-constructed. Multivariate regression models with generalized estimating equation (GEE) correction detected that the individuals carrying one copy of haplotype 677C-1298C had significantly lower diastolic and systolic blood pressure response (DeltaDBP and DeltaSBP) to benazepril treatment (p= 0.003 and p =0.043, respectively), in comparison to those without haplotype 677C-1298C. The results of family-based association test further confirmed that haplotype 677C-1298C was more frequently transmitted in subjects with either lower residual of DeltaDBP or DeltaSBP. For residual of DeltaDBP, the p-values are 0.007 in an additive model and 0.005 in a dominant model. For residual of DeltaSBP, the p-values are 0.009 in an additive model and 0.006 in a dominant model. Our findings suggest that MTHFR 677C-1298C haplotype modulate blood pressure responsiveness to shortterm treatment of ACE inhibitor in Chinese essential hypertensive patients.
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Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Benzazepinas/uso terapéutico , Hipertensión/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Benzazepinas/farmacología , Presión Sanguínea/efectos de los fármacos , Familia , Femenino , Haplotipos , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
The molecular mechanisms underlying essential hypertension are not fully elucidated. Although Benazepril is being widely used in antihypertensive medication, the agent is efficacious in only a portion of hypertensive patients. To evaluate the interaction of alpha-adducin gene Gly460Trp and angiotensin I-converting enzyme (ACE) gene I/D polymorphisms in regard to baseline blood pressure (BP) levels and the reductions of blood pressures after Benazepril treatment, we conducted an investigation of 954 Chinese hypertensive patients in Anhui province, China. We found that compared with the baseline systolic BP (SBP) of subjects with one ACE I allele and one alpha-adducin Trp allele, the baseline SBP of those with ACE DD and alpha-adducin Gly/Gly genotypes was significantly higher [Crude: beta(SE) = 7.83(3.09), p = .01; Adjusted: beta(SE) = 5.83(2.83), p = .04]. However, no associations were found between the interaction of ACE I/D and alpha-adducin Gly460Trp polymorphisms and the baseline diastolic BP or the BP response to Benazepril treatment. Our results suggested that the interaction effect of alpha-adducin Gly460Trp and ACE I/D polymorphisms might play a significant role in regulating baseline BP but not BP response to Benazepril.
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Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Benzazepinas/administración & dosificación , Proteínas de Unión a Calmodulina/genética , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Peptidil-Dipeptidasa A/genética , Adulto , Pueblo Asiatico/genética , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/genética , Resistencia a Medicamentos/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
OBJECTIVE: To explore the influence of alcohol consumption during ACEI (Benazepril) therapy on effectiveness of antihypertensive in male patients with essential hypertension. METHODS: A prospective cohort study was made and multiple linear regression and multiple logistic regression models were applied to data analysis. RESULTS: After 15 days ACEI therapy, the decrease in systolic blood pressure (deltaSBP) and diastolic blood pressure (deltaDBP) in alcohol-drinking groups was clearly smaller than that of non-drinking group. An inverse dose-response relation between alcohol drinking and (deltaSBP) as well as (deltaDBP) was observed either. To the non-alcohol-drinking group, subjects with alcohol-drinking more than 50 ml per day showed 5.26 mmHg (0.70 kPa) (P = 0.0116) and 3.32 mmHg (0.44kPa) (P = 0.0349) decreased in NSBP and DDBP, respectively. Logistic regression analysis demonstrated that the alcohol-drinking group's effect rate of antihypertensive were 45% lower (P = 0.0493) in SBP drop and 76% lower (P = 0.4750) in DBP drop respectively compared with non-and alcohol-drinking groups. CONCLUSION: Alcohol drinking during ACEI therapy can lower the effectiveness of antihypertensive in male patients with essential hypertension.
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Consumo de Bebidas Alcohólicas/efectos adversos , Antihipertensivos/uso terapéutico , Benzazepinas/uso terapéutico , Hipertensión/tratamiento farmacológico , Adulto , China , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: There is considerable variability in individual response to antihypertensive agents. The reason for this is not known, but may be related to individual genetic variability. This study examined whether the therapeutic efficacy of benazepril on essential hypertension is modified by beta2 adrenergic receptor gene (ADRB2) Arg16Gly (R16G) polymorphism. METHODS AND RESULTS: We conducted a family-based study of 321 and 610 hypertensive subjects from Yuexi and Huoqiu Counties of Anhui, China, respectively. Both systolic and diastolic blood pressures (SBP and DBP) before and after a 15-day benazepril treatment were measured. ADRB2 R16G genotypes were determined for all subjects. ADRB2 G16 allele frequency was found to be 41.0% and. 47.4% in Huoqiu and Yuexi, respectively. In Yuexi family-based association test (FBAT) revealed that the G16 allele was associated with a greater DBP decrease in response to a 15-day benazepril treatment (Z = 2.12, P = 0.03), and the data were consistent with a dominant inheritance model. A similar trend was observed in Huoqiu Chinese, but the magnitudes of effects were smaller and did not reach statistical significance. The FBAT results were further confirmed by using a generalized estimating equation model. CONCLUSION: Our family-based study provided the first evidence that ADRB2 R16G polymorphism may play an important role in DBP response to benazepril treatment, although the magnitude of the effect appears to be modified by other risk factors such as plasma lipid and glucose profiles.
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Antihipertensivos/uso terapéutico , Benzazepinas/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Polimorfismo Genético , Receptores Adrenérgicos beta 2/genética , Adulto , Pueblo Asiatico/genética , Femenino , Genotipo , Humanos , Hipertensión/etnología , Masculino , Persona de Mediana EdadRESUMEN
We investigated associations of the Gly460Trp polymorphism of the alpha-adducin gene and concentrations of serum total bilirubin, serum direct bilirubin and serum unconjugated bilirubin in patients with essential hypertension from Anhui, China from September 2000 to January 2001. Compared to women with the Gly/Gly genotype and after adjustment for important covariates, women with the Trp/Trp genotype had lower mean concentrations of serum total bilirubin (beta = -1.2 micromol/L; P = 0.01), serum direct bilirubin (beta = - 0.4 micromol/L; P = 0.02) and serum unconjugated bilirubin (P = -0.8 micromol/L; P = 0.03). Among women in either the upper or lower quartiles of serum total bilirubin, serum direct bilirubin and serum unconjugated bilirubin and compared to those with the Gly/Gly genotype, women with the Trp/Trp genotype had higher odds of being in the lower quartile of concentrations of serum total bilirubin (odds ratio = 4.0; 95 percent confidence interval: 1.6 - 10.2; P < 0.01), serum direct bilirubin (odds ratio = 4.0; 95 percent confidence: 1.6 - 9.7; P < 0.01) and serum unconjugated bilirubin (odds ratio = 2.7; 95 percent confidence interval: 1.1 - 6.7; P = 0.03) after adjustment for important covariates. We did not observe any significant associations in these models for men. We concluded that the Trp/Trp genotype of alpha-adducin Gly460Trp was associated with lower serum bilirubin concentrations in this group of Chinese women with essential hypertension. Women with the Trp/Trp genotype of alpha-adducin Gly460Trp might have increased risk for cardiovascular diseases due to lower concentrations of serum bilirubin.
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Bilirrubina/sangre , Proteínas de Unión a Calmodulina/genética , Hipertensión/genética , Polimorfismo Genético , Adulto , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: Elevated plasma homocysteine has been implicated as a risk factor for hypertension. C677T polymorphism in methylenetetrahydrofolate reductase gene (MTHFR) is a major determinant of hyperhomocysteinemia, which results in endothelial dysfunction. Angiotensin-converting enzyme (ACE) inhibitors appear to remedy the endothelial dysfunction and restore endothelium-dependent vasodilatation. The co-existence of genetic polymorphisms in drug metabolizing enzymes, targets, receptors, and transporters may influence the drug efficacy. The purpose of this study was to investigate whether short-term blood pressure control by benazepril, an ACE inhibitor, was modulated by C677T MTHFR gene polymorphism. METHODS AND RESULTS: A total of 444 hypertensive patients, aged 27 to 65 years, without any anti hypertensive therapy within 2 weeks were included. All of them were treated orally with benazepril at a single daily fixed dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. Among them, the frequency of MTHFR C677T genotype CC, CT and TT was 24.3%, 51.8%, and 23.9%, respectively. In a recessive model (CC+CT versus TT genotype), both baseline diastolic blood pressure (DBP) and diastolic blood pressure response (DeltaDBP) were significantly higher in patients with the TT genotype than in those with the CT or CC genotype (P value=0.0076 for DBP, and P value=0.0005 for DeltaDBP). We further divided all patients into three groups based on the tertiles of the DeltaBP distribution. Compared to subjects in the lowest tertile of DeltaDBP, the adjusted relative odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI, 1.4 to 4.9). However, baseline systolic blood pressure (SBP) and SBP response did not significantly associate with MTHFR C677T polymorphism. CONCLUSIONS: Our finding suggests that MTHFR C667T polymorphism modulated baseline DBP and DBP responsiveness by short-term treatment of ACE inhibitor in Chinese essential hypertensive patients.
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Benzazepinas/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Predisposición Genética a la Enfermedad/epidemiología , Pruebas Genéticas/métodos , Hipertensión/tratamiento farmacológico , Hipertensión/enzimología , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Adulto , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Sanguínea/genética , China/epidemiología , Femenino , Predisposición Genética a la Enfermedad/genética , Variación Genética , Humanos , Hipertensión/diagnóstico , Hipertensión/genética , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Pronóstico , Medición de Riesgo/métodos , Factores de Riesgo , Estadística como Asunto , Resultado del TratamientoRESUMEN
Nicotine is the major addictive substance in cigarettes, and genes involved in sensing nicotine are logical candidates for vulnerability to nicotine addiction. We studied six single-nucleotide polymorphisms (SNPs) in the CHRNA4 gene and four SNPs in the CHRNB2 gene with respect to nicotine dependence in a collection of 901 subjects (815 siblings and 86 parents) from 222 nuclear families with multiple nicotine-addicted siblings. The subjects were assessed for addiction by both the Fagerstrom Test for Nicotine Dependence (FTND) and the Revised Tolerance Questionnaire (RTQ). Because only 5.8% of female offspring were smokers, only male subjects were included in the final analyses (621 men from 206 families). Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at two SNPs, rs1044396 and rs1044397, in exon 5 of the CHRNA4 gene were significantly associated with a protective effect against nicotine addiction as either a dichotomized trait or a quantitative phenotype (i.e., age-adjusted FTND and RTQ scores), which was consistent with the results of the global haplotype FBAT. Furthermore, the haplotype-specific FBAT showed a common (22.5%) CHRNA4 haplotype, GCTATA, which was significantly associated with both a protective effect against nicotine addiction as a dichotomized trait (Z=-3.04, P<.005) and significant decreases of age-adjusted FTND (Z=-3.31, P<.005) or RTQ scores (Z=-2.73, P=.006). Our findings provide strong evidence suggesting a common CHRNA4 haplotype might be protective against vulnerability to nicotine addiction in men.
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Haplotipos/genética , Polimorfismo de Nucleótido Simple/genética , Receptores Nicotínicos/genética , Tabaquismo/genética , Adulto , ADN/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nicotina/efectos adversos , Núcleo Familiar , Hermanos , Encuestas y Cuestionarios , Tabaquismo/etiologíaRESUMEN
Individual variation in drug response is considered to have multiple origins arising from interactions among susceptible genes and environmental factors. A total of 726 hypertensive patients who took benazepril 10 mg once a day for 15 days and their families from Huoqiu county of Anhui Province, China, were used to study the association between D919G polymorphism of methionine synthase (MTR) gene and the antihypertensive effect of this angiotensin-converting enzyme inhibitor. Compared to the 919D allele, both population-based ( P=0.010) and family-based association tests (additive model P=0.018, dominant model P=0.025) demonstrated that the 919G allele was associated with a significantly less diastolic blood pressure reduction. No significant association was found between the extent of systolic blood pressure reduction and benazepril therapy. Our finding suggests that the D919G polymorphism of the MTR gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril therapy in hypertensive patients of Anhui Province, China.
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5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , Benzazepinas/farmacología , Polimorfismo Genético , Adulto , Anciano , Alelos , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , China , Ambiente , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , PresiónRESUMEN
PURPOSE: Essential hypertension, as a complex disorder with unknown etiology cause, is a major public health problem worldwide. Patients need constant drug therapy to maintain their blood pressure in a normal range. However, the current facts suggest that the treatment is not optimized in a large number of patients, and as a result they are at risk for compliance resulting in uncontrolled blood pressure. Genetic and environmental factors associated with individual variation in response to anti-hypertensive drug remain largely unknown. METHODS: In order to illustrate the existence and to attempt to identify the factors modifying drug effect, we conducted a large-scale follow-up study in two Chinese rural counties differing in both genetic background and residential environment. Hypertensive patients were treated with benazepril, a commonly used angiotensin converting enzyme inhibitor, for 15 days, and the end-point effect was evaluated. RESULTS: We found that there were large and significant differences in drug response between subjects from two counties, even after adjustment for known factors. The responses to benazepril, measured in diastolic blood pressure drop, in male patients from Yuexi was twice as effective as their counterparts from Huoqiu. CONCLUSIONS: These results suggest that adjustment of treatment regimen is necessary to improve efficacy, and it could be done at the population level to make it more feasible and affordable.
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Antihipertensivos/uso terapéutico , Benzazepinas/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Salud Rural/estadística & datos numéricos , Adulto , Composición Corporal/fisiología , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/epidemiología , Entrevistas como Asunto , Modelos Lineales , Masculino , Persona de Mediana Edad , Farmacoepidemiología , Resultado del TratamientoRESUMEN
The interleukin-1beta (IL-1beta) is an important pro-inflammatory cytokine in a broad spectrum of physiological processes. Previous investigations have observed that levels of the IL-1beta were higher in essential hypertensive patients and the IL-1beta gene polymorphism has been shown to be related to IL-1 production. We hypothesized that genetically determined differences in activity or responsiveness of cytokine(s) might contribute to hypertension. In this report, we utilized a family-based design to test the association between the IL-1beta C(-511)T polymorphism and blood pressure levels in hypertensive patients chosen from rural communities in Anhui, China. In men, carriers of the IL-1beta (-511)*C allele were found to have lower systolic (P = 0.049) blood pressure levels compared with T homozygotes, which conforms to an additive effect model. By contrast, no significant association between the IL-1beta gene and blood pressure levels was revealed in women. Our results suggested a significant role of the IL-1beta C(-511)T polymorphism in the control of blood pressure in Chinese hypertensives.
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Pueblo Asiatico/genética , Presión Sanguínea/genética , Hipertensión/genética , Interleucina-1/genética , Polimorfismo Genético/genética , Citosina/metabolismo , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Interleucina-1/sangre , Masculino , Persona de Mediana Edad , Mutación/genética , Caracteres Sexuales , Timina/metabolismoRESUMEN
OBJECTIVES: Obesity is a complex trait that is affected by both environmental and genetic risk factors. The beta(3) adrenergic receptor (ADRB3) is expressed in adipose tissue and plays a role in energy metabolism. A missense mutation on codon 64 of this gene (W64R) is associated with receptor malfunction. Previous studies examining the relation between this polymorphism and obesity produced inconsistent findings. The current study assessed the association between the W64R genotype and obesity-related phenotypes, including body weight, BMI, and serum triglycerides, cholesterol, and glucose. RESEARCH METHODS AND PROCEDURES: We determined the ADRB3 W64R genotypes and fasting serum lipid and glucose concentrations for 695 hypertensive adults (336 men,359 women) from a rural county in Anhui Province, China. Multivariate linear regression models were fit to detect associations between the genetic polymorphism and obesity-related phenotypes. RESULTS: The ADRB3 W64R polymorphism was significantly associated with body weight and BMI in men but not in women. After controlling for potential confounding variables, men who were homozygous for the R64 allele were 11.8 kg heavier (p < 0.001) and had a BMI that was 3.7 kg/m(2) greater (p = 0.001) than men who were homozygous for the W64 allele. Serum concentrations of lipids and glucose were found not associated with the genetic polymorphism. DISCUSSION: The ADRB3 R64 allele was associated with increased body weight and BMI in men but not in women. The genetic association was not modified by triglyceride, cholesterol, blood glucose, or blood pressure levels of the subjects.