Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “population stratification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed2006

Admixture in Mexico City: implications for admixture mapping of type 2 diabetes genetic risk factors.

Admixture mapping is a recently developed method for identifying genetic risk factors involved in complex traits or diseases showing prevalence differences between major continental groups. Type 2 diabetes (T2D) is at least twice as prevalent in Native American populations as in populations of European ancestry, so admixture mapping is well suited to study the genetic basis of this complex disease. We have characterized the admixture proportions in a sample of 286 unrelated T2D patients and 275 controls from Mexico City and we discuss the implications of the results for admixture mapping studies. Admixture proportions were estimated using 69 autosomal ancestry-informative markers (AIMs). Maternal and paternal contributions were estimated from geographically informative mtDNA and Y-specific polymorphisms. The average proportions of Native American, European and, West African admixture were estimated as 65, 30, and 5%, respectively. The contributions of Native American ancestors to maternal and paternal lineages were estimated as 90 and 40%, respectively. In a logistic model with higher educational status as dependent variable, the odds ratio for higher educational status associated with an increase from 0 to 1 in European admixture proportions was 9.4 (95%, credible interval 3.8-22.6). This association of socioeconomic status with individual admixture proportion shows that genetic stratification in this population is paralleled, and possibly maintained, by socioeconomic stratification. The effective number of generations back to unadmixed ancestors was 6.7 (95% CI 5.7-8.0), from which we can estimate that genome-wide admixture mapping will require typing about 1,400 evenly distributed AIMs to localize genes underlying disease risk between populations of European and Native American ancestry. Sample sizes of about 2,000 cases will be required to detect any locus that contributes an ancestry risk ratio of at least 1.5.

Africa, Western↗
PubMed2003

Prediction of clinical outcome after mechanical revascularization in acute myocardial infarction by markers of myocardial reperfusion.

OBJECTIVES: We sought to evaluate and compare recently suggested parameters of reperfusion after angioplasty in acute myocardial infarction (AMI) for risk stratification during long-term follow-up. BACKGROUND: Abnormal myocardial perfusion has a detrimental impact on survival. Several parameters of reperfusion have been evaluated in controlled study populations for risk stratification. METHODS: In 253 consecutive patients undergoing intervention in AMI on a native coronary vessel, angiographic myocardial blush grade (MBG), corrected TIMI (thrombolysis in myocardial infarction) frame count (CTFC) and persistent ST-segment elevation (STE) were determined to evaluate reperfusion. This was a high-risk population, including referral for treatment failure at a primary center in 29.2%, failed thrombolysis in 22.1% and cardiogenic shock in 13.4% of cases. RESULTS: In addition to age, patient referral, LBBB and heart rate on admission, MBG 0 to 1 (odds ratio [OR] = 3.23, p < 0.001), CTFC (OR = 1.01, p = 0.015) and persistent STE >2 leads (OR = 3.46, p = 0.010) were univariate predictors of mortality during a 22.1 +/- 15.6 months follow-up. Myocardial blush grade 0 to 1 (OR = 2.17, p = 0.033) and persistent STE (OR = 3.61, p = 0.017) persisted as independent predictors of mortality, whereas CTFC failed. Differences in mortality between reperfusion groups at 30 days remained throughout the complete follow-up. In sequential Cox models, the predictive power of clinical data alone for mortality (model chi-squared 55.8) was strengthened by adding MBG (model chi-squared 64.2) and ECG postintervention (model chi-squared 69.2). CONCLUSIONS: Myocardial blush grade 0 to 1 and persistent STE are independent predictors for long-term mortality after angioplasty in AMI. Corrected TIMI frame count is a less powerful predictor. Combining both parameters to consider quality of reperfusion in the myocardium at risk and extent of the infarct zone increases the predictive power.

Aged↗
PubMed1993

The visual system of the Florida garfish, Lepisosteus platyrhincus (Ginglymodi). III. Retinal ganglion cells.

The vitreal vascularization, optic nerve fiber layer and the retinal ganglion cells are examined in the Florida garfish, one of the two surviving genera of the ginglymode group of actinopterygian fishes. In the absence of a choroidal gland, a well developed system of hyaloid blood vessels overlie the inner retina. The optic nerve fiber and ganglion cell layers are integrated to form a series of alternating columns or fascicles emanating from an elongated optic nerve head. Horseradish peroxidase or cobaltous lysine infusion from the optic nerve reveals seven ganglion cell classes based on soma size and position, dendritic field size, retinal coverage and terminal stratification. Two discrete populations of giant ganglion cells with large somata and large dendritic fields stratify either within the sclerad region (type I cells) and/or within the middle region (type 2 cells) of the inner plexiform layer. Both giant ganglion cell populations (1% of total) form evenly distributed arrays with the dendritic arbor of each type covering the retina completely. Between seven and nine type 2 cells overlap the dendritic field of a single type 1 cell. Type 3 cells are small and located in the inner nuclear layer with a multistratified dendritic field terminating throughout the inner plexiform layer. Topographic analysis of the population of type 3 cells (4% of total) reveals a temporal area centralis (6.25 x 10(2) cells per mm2) and a ventral horizontal streak (6.25 x 10(2) cells per mm2). The large population of cells within the ganglion cell layer are classified as types 4, 5 and 6 based on soma size, dendritic field size and dendritic stratification and collectively these cells match the distribution of ganglion cells within the inner nuclear layer with 5.3 x 10(3) cells per mm2 in the temporal area centralis and 8.6 x 10(3) cells per mm2 in the horizontal streak. Type 7 cells possess small somata and send branches into both the inner and outer plexiform layers and have been termed biplexiform ganglion cells. Phylogenetic comparisons of several morphological features of the garfish retina reveals the polarity, conservation and the evolution of a number of visual characters.

Animals↗
PubMed2005

Epidemiology of severe trauma among status Aboriginal Canadians: a population-based study.

BACKGROUND: Aboriginal Canadians are considered to be at increased risk of major trauma. However, population-based studies characterizing the distribution, determinants and outcomes of major trauma in this group are lacking. We sought to measure the impact of ethnicity, as reflected by Aboriginal status, on the incidence of severe trauma and to broadly define the epidemiologic characteristics of severe trauma among status Aboriginal Canadians in a large health region. METHODS: This population-based, observational study involves all adults (people > or = 16 years) resident in the Calgary Health Region between Apr. 1, 1999, and Mar. 31, 2002. Stratification of the population into status Aboriginal Canadians and the reference population was performed by Alberta Health and Wellness using an alternate premium arrangement field within the personal health care number. Injury incidence was determined by identifying all injuries with severity scores of 12 or greater in the Alberta Trauma Registry, regional corporate data and the Office of the Medical Examiner. RESULTS: Aboriginal Canadians were at much higher risk than the reference population in the Calgary Health Region of sustaining severe trauma (257.2 v. 68.8 per 100,000; relative risk [RR] 3.7, 95% confidence interval [CI] 3.0-4.6). Aboriginal Canadians were found to be at significantly increased risk of injuries resulting from motor vehicle crashes (RR 4.8, 95% CI 3.5-6.5), assault (RR 11.1, 95% CI 6.2-18.6) and traumatic suicide (RR 3.1, 95% CI 1.4-6.1). A trend toward higher median injury severity scores was observed among Aboriginal Canadians (21 v. 18, p = 0.09). Although the case-fatality rate among Aboriginal Canadians was less than half that in the reference population (14/93 [15%] v. 531/1686 [31%], p < 0.0001), population mortality was almost 2 times greater (RR = 1.8, 95% CI 1.0-3.0, p = 0.046). INTERPRETATION: Severe trauma disproportionately affects Aboriginal Canadians.

Adolescent↗
PubMed1993

[Why do we make mistakes in identifying risk patients?].

Risk stratification studies, which are aimed at early identification of patients at high risk of clinical complications, are based on comparatively complex techniques for the analysis of retrospectively collected clinical data. Many of these studies contain serious misconceptions and errors in their analysis. This paper is a methodological review which lists the most frequent errors and omissions in retrospective stratification studies. The paper explains the principle of receiver operator characteristics and positive and negative predictive accuracy, and demonstrates the necessity of using a representative patient population for risk stratification. The danger of misleading conclusions resulting from a multivariate analysis, and several suggestions on how to organise and evaluate these studies are also discussed.

Humans↗
PubMed1996

Risk stratification in coronary artery disease and special populations.

In patients with coronary artery disease (CAD), left ventricular (LV) function, the number of diseased vessels, and the severity of myocardial ischemia are important determinants of survival. These factors can be used to identify subsets of high-risk patients who are candidates for aggressive intervention. Among patients with LV dysfunction, those with left main CAD, three-vessel disease, and one- or two-vessel disease with inducible ischemia are at highest risk. High-risk subsets among those with preserved LV function include patients with left main CAD and those with inducible ischemia and either three-vessel disease or two-vessel disease with involvement of the proximal left anterior descending coronary artery. Thus, exercise testing, assessment of ventricular function and, in selected patients, coronary angiography to determine coronary anatomy are valuable tools in risk stratification. In the primary-care setting, patient characteristics such as gender, race, age, and concomitant medical conditions may also be most useful in identifying high-risk patients. Although women in general have some primary protection against premature CAD, especially prior to the menopause, coronary risk in women who have experienced a cardiovascular event is similar to that in men. Coronary mortality is increased in minority populations, and the presence of other risk factors, such as diabetes and hyperlipidemia, can further increase this risk. Up to 80% of diabetic patients die of cardiovascular disease, 75% of which is CAD. The risk in this population is exacerbated by the abnormalities in lipid metabolism associated with the diabetic state. CAD mortality increases with aging, but it is recommended that elderly patients with CAD also receive risk factor intervention, such as cholesterol-lowering therapy. Consideration of the impact of such therapy on quality of life is especially important in initiating such interventions in the older population.

Black or African American↗
PubMed2006

Predictability of disease progression in amyotrophic lateral sclerosis.

The aim of this study was to determine the predictors of disease progression in a group of 832 patients with the diagnosis of definite or probable amyotrophic lateral sclerosis (ALS). Disease progression was defined as the time to 20-point change in Appel ALS (AALS) score. The effects of individual prognostic factors on disease progression were assessed with the Kaplan-Meier life-table method. In addition, the prognostic value of each factor was estimated using both univariate and multivariate Cox proportional hazard analyses. The median time to a 20-point change in AALS score in our patient population was 9 months. Age, site of symptom onset, time between first symptom and first examination, total AALS score at first examination, and AALS preslope (rate of disease progression between first symptom and first examination) were significant and independent covariates of disease progression in our population. Identification of predictors of disease progression will facilitate better design of therapeutic trials, permitting the use of disease progression as a primary endpoint and improving baseline stratification of patient populations.

Adult↗
PubMed2004

Lack of genetic association of the three more common polymorphisms of CARD15 with psoriatic arthritis and psoriasis in a German cohort.

OBJECTIVE: To determine whether the three common independent sequence variants of the putative pleiotropic non-MHC autoimmune gene CARD15 influence disease susceptibility in large German cohorts of patients with psoriatic arthritis and psoriasis vulgaris, before and after stratification to HLA-C. METHODS: DNA was obtained from 375 patients with psoriatic arthritis, 281 patients with psoriasis vulgaris without joint involvement, and 376 controls. The three variants of the CARD15 gene (R702W, G908R, leu1007fsinsC), and two single nucleotide polymorphisms of the HCR gene (HCR-325, HCR-2327) for HLA-C stratification were genotyped using allelic discrimination Taqman assays. RESULTS: No significant differences in genotype frequencies were observed between controls and either the psoriatic arthritis or the psoriasis vulgaris patient population, even after stratification to HLA-C in both patient cohorts, or to the type of joint involvement within the psoriatic arthritis group. CONCLUSIONS: The lack of genetic association between the most common Crohn's disease alleles of the CARD15 gene and psoriatic joint disease on large cohorts of white patients does not support a recently claimed role for CARD15 as the first non-MHC susceptibility gene in the pathogenesis of psoriatic arthritis, but confirms and extends previous studies in the case of psoriasis vulgaris.

Adolescent↗
PubMed2005

[Epidemiology of sudden cardiac death].

Sudden cardiac death remains a major challenge that we are still facing today. The complexity of the trigger mechanisms makes it difficult to achieve a reliable identification of high-risk patients. Three suggestions are made that might help to overcome this epidemiological catastrophe "Sudden Cardiac Death". 1. In patients with known heart disease risk stratification has to be improved by developing new methods to identify specifically those individuals, who are at risk for sudden rather than non-sudden cardiac death. 2. The general population contains an unknown proportion of individuals with advanced coronary disease, which is commonly asymptomatic. In these so called "normal population" classical risk stratification does not work. However, since there is a close relationship between the prevalence of risk factors for coronary disease and sudden death, a consequent treatment of risk factors should have a positive effect on sudden death rate as well. 3. The success rate of resuscitation has to be improved by strengthening each single link of the "chain of survival". Laypersons trained in basic and advanced life support techniques have to play a much major role on this scene.

Cardiomyopathies↗
PubMed2000

Indications for surgical intensive care unit admission of postoperative urologic patients.

OBJECTIVES: To analyze the practice of surgical intensive care unit (SICU) admission of postoperative urologic patients and to define objective criteria to predict active treatment requirements and length of stay in the SICU. METHODS: The records of 90 consecutive patients admitted to the SICU postoperatively in the 12-month period from January 1996 to December 1996 were retrospectively reviewed. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score was calculated from patient parameters acquired within the first 12 hours. The correlation of outcome variables to the length of stay and the requirements for active treatment in the SICU were analyzed and used to develop a risk stratification model. This algorithm was subsequently validated on a population of 46 patients who underwent radical cystectomy the following year. RESULTS: Only the preoperative American Society of Anesthesia class, the event of an intraoperative complication, and the APACHE II score were statistically significant (P <0.05) predictors of length of stay and active treatment. The patients were subsequently categorized into high and low-risk groups, which were found to have mean SICU stays of 39.9 +/- 3.92 hours and 20.2 +/- 0.45 hours, respectively (P = 0. 001), and an active SICU-specific treatment rate of 58.0% and 14.3%, respectively (P = 0.001). These results were confirmed in the validation population. CONCLUSIONS: Postoperative risk stratification may be helpful in predicting SICU requirements in the immediate postoperative period and in identifying patients at lower or higher risk of an adverse outcome.

APACHE↗
PubMed2002

Stratifying medical and pharmaceutical administrative claims as a method to identify pediatric asthma patients in a Medicaid managed care organization.

Claims data are a problematic indicator of underlying clinical diagnosis. They are attractive because of their affordability, a criterion especially salient in resource-shy environments such as the Medicaid Managed Care Organization. This study tested the validity of administrative medical and pharmaceutical claims stratified by treatment modality to identify true pediatric asthma patients. Primary and secondary data were used. Secondary data consisted of 1997 medical and pharmaceutical claims. Primary data consisted of chart data collected through expert chart review. We stratified claims by treatment modality hypothesized to better identify true asthma patients. Claim patterns were analyzed for support of expectations. Expert chart review determined true asthma status on study sample. We found that claims are patterned in accordance with hypotheses about stratification groups. The combined use of both medical and pharmaceutical claims was more effective in identifying asthmatics than the use of either set of claims by itself. The Medicaid Managed Care Organization can begin to identify its asthma population using the stratification meth.

Asthma↗
PubMed2026

Development and external validation of an explainable machine learning model for predicting chronic kidney disease progression in the Korean population.

BACKGROUND: Current risk stratification models, such as the Kidney Failure Risk Equation (KFRE), exhibit variable performance across ethnic groups and fail to capture dynamic clinical trajectories. This study aimed to develop and validate a Korean-specific machine learning (ML) model for predicting chronic kidney disease (CKD) progression using an ensemble approach. METHODS: We used electronic health records from Seoul National University Hospital for model development (n = 28,209) and the Korean Genome and Epidemiology Study (KoGES) CKD cohort for external validation (n = 3,960). The primary outcome was a composite of &#x2265;40% decline in estimated glomerular filtration rate (eGFR) or progression to end-stage renal disease within 2 years. A soft-voting ensemble of four ML algorithms (XGBoost, LightGBM, CatBoost, and Random Forest) was developed. RESULTS: The ensemble model demonstrated robust discrimination in internal validation (area under the receiver operating characteristic curve [AUROC], 0.939; 95% confidence interval [CI], 0.934-0.944), significantly exceeding the KFRE (AUROC, 0.879-0.884). External validation in the KoGES cohort showed comparable discrimination (AUROC, 0.859; 95% CI, 0.798-0.914) versus KFRE (four-variable AUROC, 0.882; 95% CI, 0.818-0.935). Shapley Additive exPlanations (SHAP) analysis identified baseline eGFR, serum creatinine, eGFR slope, albumin, and hemoglobin as key prognostic features, supporting a complementary framework using KFRE for community screening and the ML model for hospital-based risk stratification. CONCLUSION: The ensemble ML model accurately predicts short-term CKD progression in Korean patients. By incorporating longitudinal features and ensemble learning, it provides a precise alternative to Western-derived equations, particularly in tertiary care settings.

Chronic kidney failure↗
PubMed2000

Removing the sampling restrictions from family-based tests of association for a quantitative-trait locus.

One strategy for localization of a quantitative-trait locus (QTL) is to test whether the distribution of a quantitative trait depends on the number of copies of a specific genetic-marker allele that an individual possesses. This approach tests for association between alleles at the marker and the QTL, and it assumes that association is a consequence of the marker being physically close to the QTL. However, problems can occur when data are not from a homogeneous population, since associations can arise irrespective of a genetic marker being in physical proximity to the QTL-that is, no information is gained regarding localization. Methods to address this problem have recently been proposed. These proposed methods use family data for indirect stratification of a population, thereby removing the effect of associations that are due to unknown population substructure. They are, however, restricted in terms of the number of children per family that can be used in the analysis. Here we introduce tests that can be used on family data with parent and child genotypes, with child genotypes only, or with a combination of these types of families, without size restrictions. Furthermore, equations that allow one to determine the sample size needed to achieve desired power are derived. By means of simulation, we demonstrate that the existing tests have an elevated false-positive rate when the size restrictions are not followed and that a good deal of information is lost as a result of adherence to the size restrictions. Finally, we introduce permutation procedures that are recommended for small samples but that can also be used for extensions of the tests to multiallelic markers and to the simultaneous use of more than one marker.

Alleles↗
PubMed2005

Assessing the validity of cardiac surgery risk stratification systems for CABG patients in a single center.

BACKGROUND: Most cardiac surgery risk stratification systems were primarily designed using patient-related factors to predict mortality and postoperative morbidity. Relative mortality rates are higher at cardiac surgery centers which perform surgery on elderly patients. Our aim was to assess the validity of risk stratification systems for our regional population. MATERIAL/METHODS: The study involved 1021 patients. Risk stratification was carried out using the EuroSCORE, Ontario, and QMMI scoring systems. Analysis comparing the scoring systems included sensitivity, specificity, predictive values, and receiver operating characteristics (ROC) curves. Accuracy was assessed using the systems' ability to avoid Type I and Type II errors. RESULTS: Sensitivity and specificity of the QMMI scoring system were 33.3% and 97.2%, of EuroSCORE 20.7% and 96.7%, and of Ontario 21.1% and 94.4%, respectively. The best positive predictive value was for QMMI and EuroSCORE with 75% versus Ontario's 50%. The highest negative predictive value was QMMI's 85.4% versus Ontario's 78.9% and EuroSCORE's 72.0%. The best accuracy showed QMMI scoring with 84.5% versus Ontario's 78.9% and EuroSCORE's 72.2%. CONCLUSIONS: All the investigated risk stratification systems were moderately predictive. The QMMI score showed the best predictive characteristics (sensitivity, specificity, and accuracy) for our patient population. The QMMI system had high specificity and accuracy. The EuroSCORE system showed mortality overprediction for our population, associated with high false negative test results and low accuracy. The Ontario risk stratification system often commits Type II errors, associated with a high rate of false positive test results and low accuracy.

Age Factors↗
PubMed2002

Insulin resistance and upper-normal glucose levels in hypertension: a review.

Reduced insulin-mediated glucose disposal, indicative of insulin resistance, has been demonstrated in lean male hypertensives both with the hyperinsulinaemic euglycaemic clamp and the insulin suppression test. In lean hypertensives, insulin resistance was not accompanied by increases in fasting plasma insulin and glucose levels; but with modest hyperglycaemia and hyperinsulinaemia after a glucose load. Population studies (no stratification) reveal that: (1) insulin sensitivities vary widely in normotensives and hypertensives, (2) there are hypertensives and normotensives with similar degrees of insulin resistance, (3) not all hypertensives are insulin resistant, and (4) insulin resistance does not contribute to the blood pressure level of the hypertensive population. In large cross-sectional studies, the clustering of obesity, dyslipidaemia and type 2 diabetes is largely responsible for the observed associations between insulin or insulin resistance and hypertension. Recent studies indicate a role of glucose in blood pressure control. Glucose has been shown to elevate blood pressure in the presence of endothelial dysfunction and glucose values in the upper-normal range have been shown to be associated with increased cardiovascular mortality. Since endothelial dysfunction is present in hypertensives, dyslipidaemic, obese and in glucose intolerant individuals, lowering of high-normal glucose levels becomes a new, additional therapeutic target in the management of these patients. Hyperglycaemia together with endothelial dysfunction may account for the increased incidence of hypertension in obesity and diabetes mellitus. Because of the strong association between insulin resistance, hyperglycaemia and endothelial dysfunction, and the clustering of risk factors in these subjects, we propose the lowering of high normal glucose levels as part of the therapeutic strategy to prevent cardiovascular and metabolic disease.

Diabetes Mellitus, Type 2↗
PubMed2002

Heritability of anthropometric phenotypes in caste populations of Visakhapatnam, India.

In this study, we used anthropometric data from six Andhra caste populations to examine heritability patterns of 23 anthropometric phenotypes (linear, craniofacial, and soft tissue measures) with special reference to caste differences. We obtained anthropometric data from 342 nuclear families from Brahmin, Reddy, Telaga, Nagara, Ag. Kshatriya, and Mala castes of Visakhapatnam, India. These caste groups represent the existing hierarchical stratification of Indian populations. We used a variance components approach to determine the heritability (h2) of these 23 anthropometric phenotypes (height, weight, BMI, etc.). The sample consisted of 1918 individuals ranging in age from 6 to 72 years (mean = 21.5, S.D. = 13.8). The heritabilities (h2 +/- S.E.) for all anthropometric traits for the entire sample were significant (p < 0.0001) and varied from 0.25 +/- 0.05 (BMI) to 0.61 +/- 0.05 (bizygomatic breadth) after accounting for sex, age, and caste effects. Since data on socioeconomic and nutritional covariates were available for a subset of families, we repeated the genetic analyses using this subset, which has yielded higher heritabilities ranging from 0.21 +/- 0.16 (head breadth) to 0.72 +/- 0.18 (nasal breadth). In general, craniofacial measurements exhibited higher h2 compared to linear measures. Breadth measurements and circumferences yielded more or less similar heritabilities. Age and sex effects were significant (p < 0.0001 ) for most of the traits, while the effects of caste, socioeconomic status, and nutritional status were inconsistent across the traits. In conclusion, anthropometric phenotypes examined in this study are under appreciable additive genetic influences.

Adolescent↗
PubMed2004

Long perfect dinucleotide repeats are typical of vertebrates, show motif preferences and size convergence.

Microsatellites are simple sequence repeats (SSRs) showing complex patterns of length, motif sizes, motif sequences, and repeat perfection. We studied the structure of the dinucleotide SSR population at the genome level by analyzing assembled DNA sequence across species. Three dinucleotide populations were distinguished when SSR genome frequency was analyzed as a function of repeat length and repeat perfection. A population of low-perfection SSRs was identified, which is constituted by short repeats and represents the vast majority of genomic dinucleotide SSRs across eukaryotic genomes. In turn, the highly perfect repeats are 30 to 50 times less frequent and, in addition to short repeats, also contain a long repeat population that is uniquely represented in vertebrate species. Distinctive features of this population include the modal peak in the frequency distribution of repeat length and the strong preferential usage of the repeat motifs AC and AG. These results raise the hypothesis that the ability of carrying a distinct population of long, highly perfect dinucleotide repeats in the genome is a late acquisition in chordate evolution. Our analysis also suggests that different dinucleotide repeat populations have different dynamics and are likely to be underlined by different molecular mechanisms of generation and maintenance in the genome. Thus, these observations imply that caution should be taken in extrapolating results from studies on SSR mutability and on SSR phylogenetic comparisons that do not take into account the stratification of dinucelotide populations in the eukaryotic genome.

Animals↗
PubMedDate not supplied

[Drug therapy at the beginning of the genomic era].

The individualisation of drug therapy according to the genetic profile of each patient would allow to avoid the adverse effects and to reach the maximum therapeutic efficiency, therefore an optimum risk/efficiency ratio. This desideratum has become feasible in the genomic era by identifying and mapping a true mononucleotid polymorphism signature DNA (single nucleotide polymorphism fingerprint--SNP) and by using the new technologies. The present day data regarding the polymorphism of the genetic determinants involved in the response to drugs are synthetically shown, as well as the defining of the new fields--pharmacogenetics and pharmacogenomics. Although superposable and interchangeable up to a point, the term of pharmacogenetics rather refers to the study of the variability of response to drugs according to the genetic profile, the term of pharmacogenomics being reserved to the analysis of the genome (DNA and its products, RNA and proteins), in relation with the response to drugs. The differences among the individuals concerning the pharmacokinetics and the pharmacodynamics can be explained through the polymorphism of the substrata (enzymes, carrier proteins, receptors) that explains the genetic stratification of the population. The development strategies of the drug research and of the pharmaceutical industry will certainly be modulated by the new acquisitions in the field of pharmacogenetics and pharmacogenomics, with the inherent bioethical implications. New specific drugs for the patients possessing peculiar genotypes could be synthesized, the starting off of the prealable stratification of the patients according to their genotype.

Drug Therapy↗