[Expert consensus on the strategy and measures to interrupt the transmission of schistosomiasis in China].

Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.

[Diagnosis and treatment of two imported cases with schistosomiasis haematobia in Fujian Province].

OBJECTIVE: To analyze the diagnosis and treatment of two imported cases with schistosomiasis haematobia, so as to provide insights into improving the diagnosis and treatment and avoiding misdiagnosis and mistreatment of imported schistosomiasis haematobia. METHODS: The medical records and epidemiological data pertaining to the two cases were collected. The stool and urine samples were collected for identification of Schistosoma eggs using the Kato-Katz technique and direct smear method after centrifugal precipitation, and blood samples were collected for detection of anti-Schistosoma antibody. Following definitive diagnosis, the patients were given praziquantel therapy. RESULTS: The patient 1, a Malagasy, was infected in Madagascar and returned to China for delivery. The case presented intermittent painless terminal hematuria symptoms, and showed no remarkable improvements following multiple-round treatments in several hospitals. In January 2017, she was found to be positive for anti-Schistosoma antibody, negative for feces test, and positive for S. haematobium eggs in urine test, and miracidia were hatched from eggs. Then, the case was diagnosed as schistosomiasis haematobia. Patient 2 worked in Republic of Malawi for many years, and presented intermittent painless terminal hematuria since October 2018; however, no definite diagnosis or effective treatment was received after admission to multiple hospitals. In March 2019, pathological examinations showed a number of eggs in the interstitium of the bladder mass, accompanied by a large number of eosinophils, which was consistent with schistosomiasis cystitis. In April 2019, he was tested positive for serum anti-Schistosoma antibody, negative for the fecal test, and had S. haematobium eggs in urine samples, with miracidia hatched from eggs. Then, the case was diagnosed as schistosomiasis haematobia. Following treatment with praziquantel at a dose of 60 mg/kg, all symptoms disappeared. CONCLUSIONS: Overseas imported schistosomiasis haematobia is likely to be misdiagnosed. The training pertaining to schistosomiasis control knowledge requires to be improved among clinical professionals, in order to avoid misdiagnosis and mistreatment.

[Epidemiological characteristics of imported malaria cases in Fujian Province from 2014 to 2018].

OBJECTIVE: To analyze the epidemiological characteristics of imported malaria cases in Fujian Province from 2014 to 2018, so as to provide scientific basis for the development of the control strategy for imported malaria. METHODS: The epidemiological data of malaria cases in Fujian Province from 2014 to 2018 were retrieved from the Notifiable Disease Reporting System and Parasitic Disease Information Reporting System of Chinese Center for Disease Control and Prevention, and the classification, origin of infections, temporal distribution, spatial distribution, population distribution, reporting institutions and diagnosis were analyzed. RESULTS: A total of 540 overseas imported malaria cases were reported in Fujian Province from 2014 to 2018, and all cases were laboratory-confirmed, including 398 cases with falciparum malaria, 88 cases with vivax malaria, 38 cases with ovale malaria, 14 cases with malariae malaria and 2 cases with mixed infections. There were 90.56% (489/540) of the imported malaria cases with infections in 27 African countries, 5.92% (32/540) with infections in 5 Asian countries and 3.52% (19/540) with infections in one Oceania country. There was no significant seasonal distribution of the cases, and the imported malaria cases were predominantly detected in Fuzhou City (80.00%, 432/540) and at ages of 20 to 49 years (81.48%, 440/540). Initial diagnosis was predominantly at the city-level medical institutions, and 77.96% (421/540) were diagnosed as malaria at the initial diagnosis institutions. The median duration from onset to initial diagnosis was 2 days and 70.19% (379/540) were diagnosed within 3 days of onset. The interval between initial diagnosis and definitive diagnosis was 0 day, with 85.37% (461/540) definitively diagnosed within 3 days of initial diagnosis. CONCLUSIONS: Overseas imported malaria is a continuous problem challenging the malaria elimination programme of Fujian Province. Improving the healthcare-seeking awareness and the diagnostic capability of healthcare workers, and intensifying the monitoring and management of malaria among overseas labors are strongly recommended.

[The diagnostic framework for screening Alzheimer's disease in the Chinese population].

Criteria for diagnosis of Alzheimer's disease (AD) is not available in China. The international criteria is not a proper choice due to issues such as translation and lead to low diagnostic rate and high rate of missed diagnosis. The research group of Alzheimer's Disease Chinese (ADC) reviewed knowledge and techniques in neuropsychology, neuroimaging, molecular biology, and clinical neurology, and systematically studied the detection techniques such as memory, language, visuospatial, executive function, and medial temporal lobe visual scores on MRI, and their optimal threshold and diagnostic value for the diagnosis of AD. Through a systematic review and consensus meeting, a diagnostic framework for screening AD in the Chinese population was established. Among these methods, an operational standard for clinical pathology models increased the diagnostic sensitivity by 15%. The sensitivity and specificity of screening memory impairment increased by 18.1% and 11.6%, respectively. The sensitivity of screening medial temporal lobe atrophy increased by 24.5% and missed diagnosis was decreased by 34.5%. An operational standard for clinical biology models, incorporating the latest molecular imaging and molecular biology techniques, has enabled the early diagnosis of AD in China. The framework combines a principled diagnostic guideline with an operational screening protocol, which is applicable to all clinical settings and of great significance for the early detection, early diagnosis and early treatment of AD.

[Screening and diagnostic framework of vascular dementia in Chinese population].

For lack of cognitive screening standard system and controversy over the value of imaging for cerebrovascular diseases in China, the research group of Alzheimer's Disease Chinese (ADC) studied the knowledge of neuropsychology, neuroimaging and clinical neurology, systematically reviewed the diagnostic techniques such as memory, language, visuospatial, executive, function, and magnetic resonance imaging (MRI) of cerebrovascular diseases, and their optimal threshold and diagnostic value for vascular dementia. Via a consensus meeting, the diagnostic guidelines and practical screening process are combined to construct a framework in Chinese population, which is based on the objective evidence of medical history and clinical evaluation. The diagnosis of vascular dementia is supported by imaging evidence of cerebrovascular diseases and differentiates from other causes of dementia or comorbidities. This consensus is applicable to medical units in China, and is of great significance for early detection, early diagnosis and early treatment of vascular dementia.

[Dementia screening and diagnostic framework in Chinese population].

There are no standard diagnostic criteria for Alzheimer's disease (AD) in China. The copied international criteria has led to a high rate of missed diagnosis due to issues such as translation and cultural discrepancy. Under the principles of semantic equivalence, content equivalence and performance equivalence, the research group of Alzheimer's Disease Chinese (ADC) adopted several effective methods, such as two-way translation, content conversion, performance evaluation, etc. to systematically study the cognitive, behavioral, functional, and general assessment techniques in dementia screening and diagnosis, as well as their screening thresholds and diagnostic values. We also established a dementia screening and assessment framework in clinical practice through systematic reviews and group consensus. It has improved the early diagnosis rate of dementia in China, been accepted by home and abroad academic institutions, which is of great significance for early diagnosis and treatment of dementia.

[China Hainan Centenarian Cohort Study: study design and preliminary results].

Objective: To investigate the health status, functional ability, mental psychology, health care and other longevity-related characteristics of individuals aged ≥100 years as well as risk factors in Hainan province, China. Methods: China Hainan Centenarian Cohort Study (CHCCS) is a community-based, prospective cohort study to establish multi-dimensional database consisting of questionnaire findings, anthropometric parameters and biological specimens as well as imaging features. With the household registration information provided by the Department of Civil Affairs of Hainan province, a baseline survey was conducted in centenarians in 18 counties in Hainan with the oldest old in 5 counties as controls between 2014 and 2017. The survey included face to face interview, physical examination and biological specimen collection. After the baseline survey, the participants of CHCCS were followed up at an interval of 2 years to collect the information about their living status, disease status or major death causes. Results: According to the information provided by the Department of Civil Affairs of Hainan province in 2014, the survey found that 1 473 centenarians were still living. By December 2016, 1 002 of them had agreed to be surveyed. The average age of 722 centenarians with complete information in the baseline survey was (102.7±2.7) years, the majority of them were females (83.0%), widows (88.8%), in Han ethnic group (84.5%), lived with family members (87.8%), illiterates (89.7%) and farmers (81.0%). Conclusion: CHCCS has provided longevity-related information of the large longevity population and collected the valuable and rare biological specimens with great urgency to establish an interdisciplinary platform and base for longevity, senility and healthy aging research.

Interleukin-10 does not modulate clopidogrel platelet response in mice.

UNLABELLED: ESSENTIALS: It is unclear whether interleukin-10 (IL-10) could affect clopidogrel metabolism and response. The bioactivation of and response to clopidogrel were determined between mice with or without IL-10. Maximum clopidogrel active metabolite levels were the major driver of platelet response to clopidogrel. IL-10 did not modulate maximum levels of clopidogrel active metabolite and its antiplatelet effects. BACKGROUND: Elevated plasma interleukin-10 (IL-10) levels were observed in patients who responded less to clopidogrel (a prodrug that is required for further metabolic bioactivation in the liver). However, no data are currently available suggesting whether there is such an association. OBJECTIVE: To systematically explore possible differences in the formation of and response to clopidogrel active metabolite (CAM) in mice with or without IL-10 gene expression. METHODS: A single oral dose of clopidogrel (10 mg kg(-1)) was given to IL-10 knockout (KO) mice and wild-type (WT) control mice, respectively, and pharmacokinetic parameters of clopidogrel and CAM were calculated. Moreover, adenosine diphosphate-induced whole-blood platelet aggregation was measured in mice receiving 0, 5, 10, or 20 mg kg(-1) of clopidogrel, respectively. RESULTS: Compared with IL-10 KO mice, WT mice had significantly lower area under the plasma concentration-time curve (AUC) of CAM as a result of a shorter mean elimination half-life but had significantly higher AUC of clopidogrel due to slower systemic clearance and smaller volume of distribution. Although AUC of CAM was significantly lower in WT mice than in KO mice, antiplatelet effects of clopidogrel did not differ significantly between the two mouse groups, as their maximum plasma concentrations (Cmax ) of CAM were not significantly different. CONCLUSIONS: IL-10 expression level affects AUC rather than Cmax of CAM, but the Cmax of CAM is the major driver of antiplatelet effects of clopidogrel in mice.

Limited clinical utility of genotype-guided warfarin initiation dosing algorithms versus standard therapy: a meta-analysis and trial sequential analysis of 11 randomized controlled trials.

In terms of inconsistent conclusions across all relevant randomized controlled trials (RCTs) and available meta-analyses, we aimed to use a meta-analysis and trial sequential analysis (TSA) to evaluate whether clinical utility of a genotype-guided warfarin initiation dosing algorithm could be better than that of a standard therapy regimen, and whether currently relevant evidence could be reliable and conclusive. Overall, 11 eligible RCTs involving 2677 patients were included for further analyses. Compared with fixed dose or clinically adjusted warfarin initiation dosing regimens, genotype-guided algorithms significantly increased time in therapeutic range, shortened time to first therapeutic international normalized ratio (INR) and time to stable doses, but did not show any marked improvements in excessive anticoagulation, bleeding events, thromboembolism, or all-cause mortality. Subgroup analyses revealed that, genotype-guided algorithms showed better control in the outcomes of time in therapeutic range or excessive anticoagulation than fixed-dose regimens rather than clinically adjusted regimens. Except for excessive anticoagulation, currently available evidence of all other outcomes was unreliable and inconclusive as determined with TSA. Our findings suggest that genotype-guided warfarin initiation dosing algorithms have superiority in the improvement of surrogate quality markers for anticoagulation control, but that this does not translate into statistically significant differences in clinical outcomes, which is largely because of the insufficient sample size in the RCTs analyzed.

Achieving nitrogen removal via nitrite pathway from urban landfill leachate using the synergetic inhibition of free ammonia and free nitrous acid on nitrifying bacteria activity.

In this study, a biological system consisting of an up-flow anaerobic sludge blanket (UASB) and anoxic-oxic (A/O) reactor was established for the advanced treatment of high ammonium urban landfill leachate. The inhibitory effect of free ammonia (FA) and free nitrous acid (FNA) on the nitrifying bacterial activity was used to achieve stable nitritation in the A/O reactor. The results demonstrated that the biological system achieved chemical oxygen demand (COD), total nitrogen (TN) and NH(4)(+)-N removal efficiencies of 95.3, 84.6 and 99.2%, respectively at a low carbon-to-nitrogen ratio of 3:1. Simultaneous denitritation and methanogenesis in the UASB could improve the removal of COD and TN. Nitritation with above 90% nitrite accumulation was successfully achieved in the A/O reactor by synergetic inhibition of FA and FNA on the activity of nitrite oxidizing bacteria (NOB). Fluorescence in situ hybridization (FISH) analysis showed that ammonia oxidizing bacteria (AOB) was dominant and was considered to be responsible for the satisfactory nitritation performance.

The gain-of-function variant allele CYP2C19*17: a double-edged sword between thrombosis and bleeding in clopidogrel-treated patients.

BACKGROUND: A large number of clinical studies have documented that a loss-of-function variant CYP2C19*2 affects clinical profiles of clopidogrel (efficacy and safety). However, data on the impact of a gain-of-function variant CYP2C19*17 on the response to that drug seem to be less consistent. OBJECTIVES: To systematically summarize all available clinical data assessing the role of the CYP2C19*17 variant in patients taking clopidogrel. METHODS: A literature search was conducted and a meta-analysis was performed for 11 eligible studies. The endpoints included the major adverse cardiovascular events (MACE, representing non-fatal myocardial infarction, stroke, revascularization, or death), bleeding events, mortality, stent thrombosis and high platelet reactivity (HPR). RESULTS: Data from six clinical studies demonstrated that carriers of the CYP2C19*17 variant had a marked protection against recurrent cardiovascular events in patients with coronary artery disease compared with non-carriers, as measured by a 16% decrease in the incidence of MACE (10.0% vs. 11.9%; OR, 0.82; 95% CI, 0.72-0.94; P = 0.005). On the other hand, carriers had an increased risk of developing bleeding as expected (8.0% vs. 6.5%; OR, 1.25; 95% CI, 1.07-1.47; P = 0.006; four studies). Moreover, the presence of the CYP2C19*17 variant might lead to increased response to clopidogrel, as shown by a marked lower prevalence of HPR in carriers than in non-carriers (37.9% vs. 50.8%; OR, 0.60; 95% CI, 0.45-0.79; P = 0.0003; three studies). CONCLUSIONS: Carriers of the CYP2C19*17 variant have greater therapeutic responsiveness to clopidogrel than non-carriers, but they have an increased risk of developing bleeding as well.

Integration of diverse data sources for prediction of adverse drug events.

The rapid evolution of large biological, pharmacological, and chemical databases has led to optimism that such data resources can be leveraged for prediction of drug action based on molecular descriptors of the drug. Challenges to realize this possibility include organization of each type of database in a manner that allows extraction of information across disparate data sources and the linkage of information across the biological, pharmacological, and chemical domains.

A common beta1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to beta-blockade.

BACKGROUND: A common polymorphism of the beta(1)-adrenergic receptor Arg389Gly markedly affects function in vitro, but little is known about its in vivo significance. METHODS AND RESULTS: Resting and exercise hemodynamic responses were measured in subjects homozygous for Arg389 (n = 21) or Gly389 (n = 13) alleles before and 3 hours after administration of a beta-blocker, atenolol. Demographic characteristics and atenolol concentrations were similar in the two genotypic groups. Genotype had a marked effect on resting hemodynamic responses to atenolol, with Arg389-homozygous subjects having a larger decrease in resting systolic blood pressure (8.7 +/- 1.3 mm Hg versus 0.2 +/- 1.7 mm Hg, P < .001) and mean arterial blood pressure (7.2 +/- 1.0 mm Hg versus 2.0 +/- 1.7 mm Hg, P = .009). Attenuation of exercise-induced hemodynamic responses by atenolol was not affected by genotype. CONCLUSIONS: There is reduced sensitivity of Gly389 homozygotes to a beta-adrenergic receptor antagonist, and this polymorphism may be an important determinant of variability in response to beta-blockade.

In-vivo effects of Glu298Asp endothelial nitric oxide synthase polymorphism.

Endothelial nitric oxide synthase catalyses the formation of the vasodilator nitric oxide, a major regulator of vascular tone. The Asp298 polymorphism of the nitric oxide synthase gene is associated with altered function and expression of the enzyme in vitro and myocardial infarction and coronary artery spasm in vivo. We examined the effect of the Glu298Asp polymorphism on: (1) local vascular responses to phenylephrine, acetylcholine, glyceryl trinitrate and prostaglandin E1 in the dorsal hand vein; (2) changes in forearm blood flow during mental stress, a measure of nitric oxide-mediated effect on resistance vessels; (3) excretion of urinary nitrite/nitrate as a measure of total body nitric oxide production; and (4) F2-isoprostane metabolite, a measure of oxidative stress, in healthy Glu298 (n = 12) and Asp298 (n = 13) homozygotes. There were no significant differences in acetylcholine dose responses (P = 0.29) in Glu298 and Asp298 homozygotes. Responses to glyceryl trinitrate, prostaglandin E1 and the alpha-adrenergic agonist phenylephrine did not differ by genotype. Forearm blood flow was similar at rest and increased significantly (from 7.5 ml/min/100 ml to 12.2 ml/min/100 ml; P = 0.003), but similarly (P = 0.2), during mental stress in both genotypes. Asp298 homozygotes excreted significantly less nitrate/nitrite than Glu298 homozygotes (nitrate + nitrite/creatinine ratio 0.05 +/- 0.01 vs. 0.09 +/- 0.01, respectively; P < 0.005). Urinary F2-isoprostane metabolite excretion did not differ (Glu298, 2.04 +/- 0.25 ng/mg creatinine; Asp298, 1.85 +/- 0.37 ng/mg creatinine; P = 0.7). We conclude that in healthy volunteers the Glu298Asp polymorphism affects endogenous nitric oxide production without affecting nitric oxide-mediated vascular responses. This polymorphism may only have clinical significance in the presence of endothelial dysfunction.

The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization.

BACKGROUND: With continuous exposure to beta2-adrenergic agonists, vascular tissue becomes desensitized to agonist-mediated vasodilatation. We studied the effects of two common polymorphisms of the beta2-adrenergic receptor, one at codon 16 and one at codon 27, on agonist-mediated vasodilatation and desensitization in the vascular bed. METHODS: We studied 26 healthy subjects who were selected to represent three genotypes: 7 were homozygous for the alleles encoding Arg16 and Gln27, 8 were homozygous for the alleles encoding Gly16 and Gln27, and 11 were homozygous for the alleles encoding Gly16 and Glu27. Vascular responses were assessed by measuring changes in the diameter of a dorsal hand vein. A dose-response curve of the effect of the beta2-adrenergic-receptor agonist isoproterenol was constructed (dose range, 4 to 480 ng per minute). Desensitization was then induced by a 2-hour continuous infusion of isoproterenol, and venodilatation was measured 30, 60, 90, and 120 minutes after the start of the infusion. RESULTS: Subjects who were homozygous for Arg16 had almost complete desensitization; venodilatation in response to isoproterenol in this group decreased from a mean (+/-SE) of 44+/-11 percent to 8+/-4 percent (P=0.006). In contrast, subjects who were homozygous for Gly16 did not have significant desensitization, irrespective of the amino acid encoded by codon 27. Subjects who were homozygous for Glu27 had higher maximal venodilatation in response to isoproterenol than those who were homozygous for Gln27 (86+/-13 percent vs. 54+/-8 percent, P=0.03). CONCLUSIONS: The Arg16 polymorphism of the beta2-adrenergic receptor is associated with enhanced agonist-mediated desensitization in the vasculature, and the Glu27 polymorphism is associated with increased agonist-mediated responsiveness. Therefore, polymorphisms of the beta2-adrenergic receptor are potentially important determinants of the vascular response to stress.

Identification of functionally variant MDR1 alleles among European Americans and African Americans.

MDR1 (P-glycoprotein) is an important factor in the disposition of many drugs, and the involved processes often exhibit considerable interindividual variability that may be genetically determined. Single-strand conformational polymorphism analysis and direct sequencing of exonic MDR1 deoxyribonucleic acid from 37 healthy European American and 23 healthy African American subjects identified 10 single nucleotide polymorphisms (SNPs), including 6 nonsynonymous variants, occurring in various allelic combinations. Population frequencies of the 15 identified alleles varied according to racial background. Two synonymous SNPs (C1236T in exon 12 and C3435T in exon 26) and a nonsynonymous SNP (G2677T, Ala893Ser) in exon 21 were found to be linked (MDR1*2 ) and occurred in 62% of European Americans and 13% of African Americans. In vitro expression of MDR1 encoding Ala893 (MDR1*1 ) or a site-directed Ser893 mutation (MDR1*2 ) indicated enhanced efflux of digoxin by cells expressing the MDR1-Ser893 variant. In vivo functional relevance of this SNP was assessed with the known P-glycoprotein drug substrate fexofenadine as a probe of the transporter's activity. In humans, MDR1*1 and MDR1*2 variants were associated with differences in fexofenadine levels, consistent with the in vitro data, with the area under the plasma level-time curve being almost 40% greater in the *1/*1 genotype compared with the *2/*2 and the *1/*2 heterozygotes having an intermediate value, suggesting enhanced in vivo P-glycoprotein activity among subjects with the MDR1*2 allele. Thus allelic variation in MDR1 is more common than previously recognized and involves multiple SNPs whose allelic frequencies vary between populations, and some of these SNPs are associated with altered P-glycoprotein function.

Arg389Gly beta 1-adrenoceptor polymorphism varies in frequency among different ethnic groups but does not alter response in vivo.

There are marked interethnic differences in beta 1-adrenoceptor-mediated responsiveness, with sensitivity decreased in African-Americans and increased in Chinese compared with Caucasians. Therefore, the frequency of a common naturally occurring polymorphism of the human beta 1-adrenoceptor gene (Arg389Gly), which has functional importance in vitro, was determined in 194 African-Americans, 316 Caucasian-Americans, 221 Hispanic-Americans and 142 Chinese. African-Americans were found to have a significantly lower frequency of the Arg389 allele than the other three ethnic groups (all P < 0.01). In the populations studied, the order of the distribution of the Arg389 allele was: Chinese (74%) > Caucasians (72%) > Hispanics (67%) > African-Americans (58%). To determine the functional significance of the Arg389Gly beta 1-adrenoceptor polymorphism, in-vivo heart rate responses to exercise were compared in healthy subjects homozygous for the Arg (n = 9) and Gly (n = 8) alleles. Heart rate response to exercise was not affected by genotype (P = 0.4). Although ethnic differences in the frequency of the beta 1-adrenoceptor Arg389Gly polymorphism exist, the polymorphism does not appear to have functional significance in healthy subjects and therefore may not contribute to ethnic differences in response to drugs acting through the beta 1-adrenoceptor.

Hypertension in black people: study of specific genotypes and phenotypes will provide a greater understanding of interindividual and interethnic variability in blood pressure regulation than studies based on race.

Hypertension is more frequent and more severe in some Black populations. Although many studies have focused on hypertension in black people in an attempt to understand the genetic and environmental factors that regulate blood pressure, this approach has not been productive. Study of the relationship between specific phenotypes and genotypes, both within and across ethnic groups, is more likely to advance our understanding of the regulation of blood pressure than studies focused on race and blood pressure.

Molecular basis of ethnic differences in drug disposition and response.

Ethnicity is an important demographic variable contributing to interindividual variability in drug metabolism and response. In this rapidly expanding research area many genetic factors that account for the effects of ethnicity on pharmacokinetics, pharmacodynamics, and drug safety have been identified. This review focuses on recent developments that have improved understanding of the molecular mechanisms responsible for such interethnic differences. Genetic variations that may provide a molecular basis for ethnic differences in drug metabolizing enzymes (CYP 2C9, 2C19, 2D6, and 3A4), drug transporter (P-glycoprotein), drug receptors (adrenoceptors), and other functionally important proteins (eNOS and G proteins) are discussed. A better understanding of the molecular basis underlying ethnic differences in drug metabolism, transport, and response will contribute to improved individualization of drug therapy.