Gene/Protein Disease Symptom Drug Enzyme Compound
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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is increasing evidence that risk factors for vascular disease and stroke are associated with cognitive impairment and Alzheimer's disease. This paper reviews current knowledge on the relationship between risk factors for stroke and Alzheimer's disease. The focus will be on 'classical' risk factors, including age and gender, socioeconomic status, diabetes, cholesterol, prior cardiovascular disease, atrial fibrillation, cigarette smoking and alcohol use; as well as on factors that more recently have been recognized as putative risk factors, including APOE genotype, serum homocysteine concentration, relative abnormalities in the hemostatic and thrombotic systems, and inflammation.
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PMID:Risk factors for vascular disease and dementia. 1042 64

There is growing debate over the utility of multiple locus association analyses in the identification of genomic regions harboring sequence variants that influence common complex traits such as hypertension and diabetes. Much of this debate concerns the manner in which one can use the genotypic information from individuals gathered in simple sampling frameworks, such as the case/control designs, to actually assess the association between alleles in a particular genomic region and a trait. In this paper we describe methods for testing associations between estimated haplotype frequencies derived from multilocus genotype data and disease endpoints assuming a simple case/control sampling design. These proposed methods overcome the lack of phase information usually associated with samples of unrelated individuals and provide a comprehensive way of assessing the relationship between sequence or multiple-site variation and traits and diseases within populations. We applied the proposed methods in a study of the relationship between polymorphisms within the APOE gene region and Alzheimer's disease. Cases and controls for this study were collected from the United States and France. Our results confirm the known association between the APOE locus and Alzheimer's disease, even when the epsilon 4 polymorphism is not contained in the tested haplotypes. This suggests that, in certain situations, haplotype information and linkage disequilibrium-induced associations between polymorphic loci that neighbor loci harboring functional sequence variants can be exploited to identify disease-predisposing alleles in large, freely mixing populations via estimated haplotype frequency methods.
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PMID:Genetic analysis of case/control data using estimated haplotype frequencies: application to APOE locus variation and Alzheimer's disease. 1115 23

Trinidadians of South Asian origin have a high prevalence of cardiovascular disease and diabetes compared to Trinidadians of African origin. The degree to which these differences are related to genetic and/or environmental factors is unclear. To determine whether there might be a genetic basis for this difference in prevalence of deleterious phenotypes we examined allele frequencies for candidate genes in atherosclerosis and diabetes. We genotyped 81 consecutive neonates of African origin and 103 consecutive neonates of South Asian origin. We evaluated common polymorphisms in 11 candidate genes for atherosclerosis and diabetes. We found differences between the two subpopulations in the allele frequencies of several candidate genes, including APOE, LIPC, APOC3, PON1, PON2, and PPP1R3. However, the differences in the allele frequencies were not all consistent with the pattern of CHD expression between these two ethnic groups in adulthood. Thus, differences in genetic architecture alone may not explain the wide disparities in disease prevalence between these two subpopulations. It is very likely that environmental factors, or unmeasured genetic factors, influence the genetic susceptibility to disease in these subpopulations.
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PMID:Allele frequencies for candidate genes in atherosclerosis and diabetes among Trinidadian neonates. 1151 79

This article reviews the current status of our knowledge of lipoproteins, nutrition, and coronary heart disease (CHD). Special emphasis is placed on CHD risk assessment, dietary intervention studies, diet-gene interactions, and current dietary guidelines and the contributions of my laboratory to these areas. CHD remains a major cause of death and disability, and risk factors include age, sex, hypertension, smoking, diabetes, elevated serum LDL cholesterol, and low HDL cholesterol. Emerging independent risk factors include elevated serum concentrations of lipoprotein(a), remnant lipoproteins, and homocysteine. The cornerstone of CHD prevention is lifestyle modification. Dietary intervention studies support the concepts that restricting saturated fat and cholesterol and increasing the intake of essential fatty acids, especially n - 3 fatty acids, reduces CHD risk. The variability in LDL-cholesterol response to diet is large, related in part to APOE and APOA4 genotype. The use of antioxidants in intervention studies has not been shown to reduce CHD risk. Compliance with dietary recommendations remains a major problem, and directly altering the food supply may be the most effective way to ensure compliance. The available data indicate that the recommendation to use fats, oils, and sugars sparingly for CHD prevention should be modified to a recommendation to use animal, dairy, and hydrogenated fats; tropical oils; egg yolks; and sugars sparingly and to increase the use of vegetables, fruit, and whole grains.
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PMID:Lipoproteins, nutrition, and heart disease. 1181 9

This cross-sectional study tested the hypothesis that APOE genotype is a risk factor for diabetic neuropathy severity. A model with age, duration of diabetes, and APOE genotype was found to predict (p = 0.0083) severity on the Neuropathy Impairment Score in the Lower Limbs (NISLL). Considering genotype alone, patients with APOE 3/4 and 4/4 genotypes had 3 more NISLL points than patients with other genotypes. This impact on severity is equivalent to having 15 extra years of age or diabetes duration.
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PMID:APOE genotype is a risk factor for neuropathy severity in diabetic patients. 1265 74

We have tried, with only partial success, to confirm findings in a recently reported study in this journal on the relationship of APOE genotype to mortality in community representative Hispanics (n = 659), Whites (n = 272), and African-Americans (n = 450), aged 65 and over, living in Northern Manhattan, New York. That study found that using proportional hazards models adjusted for sex and lipid levels, Hispanics and Whites with the E2/E3 genotype, but not African-Americans, had the lowest mortality risk. Those under age 75 had risks comparable to those over age 75, suggesting minimal survivor bias. Nearly 50% of the mortality risk associated with the APOE genotype appeared to act through heart disease, diabetes, and stroke. The current study of African-Americans (n = 1,083) and Whites (n = 915) aged 71 and over living in the more rural Southeastern US, found no protective effect of the E2/E3 genotype for either African-Americans or Whites. Among younger Whites (age 71-75), point estimates suggested that the E2/E3 genotype might be protective, but at a nonsignificant level; self-reported African-American race, but not genotype, was a risk factor for mortality in this age group. Neither lipid level nor health condition attenuated the effect of APOE genotype. Differences in findings may reflect issues of sampling, age, the relative distribution of the APOE alleles, or some other factor. Until such time as studies use truly representative samples and include younger ages, findings in this area must be treated with caution.
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PMID:Mortality and apolipoprotein E in African-American, and White elders: an attempted replication. 1274 52

Recent evidence indicates that different vascular risk factors are present in Alzheimer's disease (AD) and other prevalent dementia types probably contributing to deterioration of cerebrovascular function, thus enhancing neurodegeneration and premature neuronal death due to a reduction in brain perfusion. Brain blood flow shows a reduced velocity and increased pulsatility (PI) and resistance indices (RI) in different types of dementia and in diabetes and hypertension, as well. High levels of diastolic blood pressure correlate with diminished brain blood flow and elevated PI and RI, accompanied by cognitive deterioration. Nitric oxide (NO) levels are found increased in the sera and brain tissue of AD patients. Vascular risk factors (hyperglycemia, LDL-cholesterol, triglycerides, hypertension) and altered brain hemodynamic parameters correlate with APOE genotypes of which APOE-4/4 carriers represent the AD population with the highest cerebrovascular risk. In addition, the genomic profiles of patients with dementia integrating AD-related genes (APOE, PS1, PS2, cFOS) in a mini-tetragenic haplotype significantly differ from controls with an absolute genetic variation of about 50%-60%. Cerebrovascular dysfunction is a factor common to most types of dementia; however, genetic variation among different dementia types might be determinant for the activation of early vascular events inducing or accelerating neurodegeneration. In this regard, cerebrovascular dysfunction should be considered a potential therapeutic target in dementia.
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PMID:Cerebrovascular risk factors in Alzheimer's disease: brain hemodynamics and pharmacogenomic implications. 1450 10

The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE epsilon4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 (hazard ratio: 2.00; 95% CI: 1.19-3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45-1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274).
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PMID:Apolipoprotein E and mortality in African-Americans and Yoruba. 1464 29

Numerous studies have demonstrated that increased C-reactive protein (CRP) levels predict coronary heart disease, stroke, peripheral vascular disease, and diabetes, and are associated with features of the metabolic syndrome. Only three previous studies have investigated the heritability of CRP levels, primarily in samples of Caucasian families. The purpose of the present study was to estimate the magnitude of genetic influences on CRP levels, and to examine potential associations between variation in the APOE gene and CRP levels, using a sample of 562 individual Japanese Americans from 68 extended kindreds. In general, correlation coefficients between first-degree relatives for CRP were approximately 0.2, and spouse correlations did not differ from zero, consistent with genetic influences. Heritability estimates were approximately 0.3 (p < 0.01), even with adjustment for factors known to influence CRP levels. A significant relationship was seen between unadjusted CRP levels and APOE genotypes (p = 0.02), with the highest mean CRP level among epsilon2 carriers (1.20 mg/L), and nearly the same mean levels among epsilon3/epsilon3 subjects and epsilon4 carriers (0.72 and 0.74 mg/L, respectively). However, this relationship was diminished with adjustment for covariates (p = 0.07). These results demonstrate the presence of both genetic and environmental effects on CRP levels among Asian Americans, and additional studies are needed to determine if the APOE gene contributes to these genetic influences.
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PMID:Heritability of C-reactive protein and association with apolipoprotein E genotypes in Japanese Americans. 1518 Jun 98

The aim of this study was to determine the association between APOE genotype and carotid atherosclerosis, defined as intimal-medial thickness (IMT) and stenosis, and to assess if other cardiovascular risk factors modify this association. A total of 1,315 men and 1,408 women from the Framingham Offspring Study underwent carotid ultrasound during examination cycle 6 and had complete data on APOE genotype. Three APOE genotype groups were defined: APOE2 (including E2/E2, E3/E2 genotypes), APOE3 (E3/E3), and APOE4 (including E4/E3, E4/E4 genotypes). Carotid IMT and the presence of carotid stenosis > 25% were determined by ultrasonography. In women, the APOE2 group was associated with lower carotid IMT (0.67 vs. 0.73 mm) and lower prevalence of stenosis (odds ratio = 0.49; 95% confidence interval = 0.30-0.81) compared with the APOE3 group. In men, APOE genotype was not associated with carotid IMT or stenosis in the whole group; however, diabetes modified the association between APOE genotype and carotid IMT (P for interaction = 0.044). Among men with diabetes, the APOE4 group was associated with a higher internal carotid artery IMT (1.22 mm) than the APOE3 group (0.90 mm) or the APOE2 group (0.84 mm). The E2 allele was associated with lower carotid atherosclerosis in women, and the E4 allele was associated with higher internal carotid IMT in diabetic men.
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PMID:Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study. 1525 98


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