Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a retrospective study of a consecutive autopsy series of 2060 elderly subjects (mean age 78.5 +/- 6.8 SD years), sporadic cerebral amyloid angiopathy (CAA) of various degrees was detected in 73.2% and in 98.5% of autopsy-confirmed cases of typical (plaque and tangle) Alzheimer disease (AD). Spontaneous (non-traumatic) intracerebral hemorrhages (ICH) (excluding microbleeds) were seen in 5.6% of the total cohort and in 7.2% of definite AD cases; CAA was found in 49% of brains without and in 48.7% with ICH which was not significantly different. The latter groups showed a significantly higher frequency of severe degrees of CAA than those without ICH (80.4 vs 30.9%, p < 0.001). Patients with CAA were older than those without CAA, showing a higher frequency of clinical dementia and pathologically confirmed AD, but signs of hypertension (history and/or autopsy) were seen in 41 and 33.6% of these cases, respectively, compared to 70-75% in patients with non-CAA related ICHs. CAA-related ICH much more frequently involved cerebral lobes or hemispheres, while non-CAA related lesions were more often located in basal ganglia and brainstem. The data of a lower prevalence of CAA in cases without than with ICH, but a similar prevalence of ICH with and without CAA do not support the concept that CAA represents the most evident risk factor for ICH in the aged. While severe degrees of CAA were indeed associated with ICH, the general prevalence of large ICH in this autopsy cohort was much higher in cases without CAA, probably due to other risk factors including hypertension, which was documented in around 40% of cases with CAA-related ICH. APOE epsilon3/4 and epsilon4/4 were significantly more frequent in AD (n = 163) than in age-matched controls (n = 47) and were associated with more severe degrees of CAA, but no general genotyping in ICHs with and without CAA was performed. Hence, the role of APOE in the pathogenesis of ICH with and without CAA needs further elucidation.
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PMID:Unexpectedly low prevalence of intracerebral hemorrhages in sporadic cerebral amyloid angiopathy: an autopsy study. 1820 17

Alzheimer's disease is the most common form of dementia in the elderly. The cause of Alzheimer's disease is still unknown and there is no cure for the disease yet despite 100 years of extensive research. Cardiovascular risk factors such as high serum cholesterol, presence of the Apolipoprotein epsilon4 (APOE epsilon4) allele and hypertension, play important roles in the development of Alzheimer's disease. We postulate that a combination of diet, lifestyle, vascular, genetic, and amyloid related factors, which enhance each other's contribution in the onset and course of Alzheimer's disease, will be more likely the cause of the disease instead of one sole mechanism. The possibility that the risk for Alzheimer's disease can be reduced by diet or lifestyle is of great importance and suggests a preventative treatment in Alzheimer's disease. Because of the great importance of lipid diets and metabolism in preventative treatment against both Alzheimer's disease and cardiovascular disease, long-chain polyunsaturated fatty acids from fish oil, ApoE genotype and cholesterol metabolism in correlation with Alzheimer's disease will be reviewed.
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PMID:Fatty acids, lipid metabolism and Alzheimer pathology. 1837 24

Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions.
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PMID:Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors. 1870 94

Myocardial infarction (MI) is an important clinical problem because of its large contribution to mortality. The main causal and treatable risk factors for MI include hypertension, hypercholesterolemia or dyslipidemia, diabetes mellitus, and smoking. In addition to these risk factors, recent studies have shown the importance of genetic factors and interactions between multiple genes and environmental factors. Disease prevention is an important strategy for reducing the overall burden of MI, with the identification of markers for disease risk being key both for risk prediction and for potential intervention to lower the chance of future events. Although genetic linkage analyses of families and sib-pairs as well as candidate gene and genome-wide association studies have implicated several loci and candidate genes in predisposition to coronary heart disease (CHD) or MI, the genes that contribute to genetic susceptibility to these conditions remain to be identified definitively. In this review, we summarize both candidate loci for CHD or MI identified by linkage analyses and candidate genes examined by association studies. We also review in more detail studies that have revealed the association with MI or CHD of polymorphisms in MTHFR, LPL, and APOE by the candidate gene approach and those in LTA and at chromosomal region 9p21.3 by genome-wide scans. Such studies may provide insight into the function of implicated genes as well as into the role of genetic factors in the development of CHD and MI.
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PMID:Molecular genetics of myocardial infarction. 1870 61

With the aim to investigate association of polymorphisms of candidate genes with clinical peculiarities of hypertensive disease in patients having burdened familial anamnesis we examined 413 (229 men and 184 women, mean age 60.3 +/- 0.59 years) patients with essential arterial hypertension (AH). Determination of alleles and genotypes of polymorphic markers of ACE, AGT, AT2R1, CYP11B2, NOS3, ENDl, GNB3, PPARA, PPARG2, MTHFR, CAT, SOD2, PON1, PON2 sigma APOB, APOE, LPL genes was carried out with the use of polymerase chain reaction. Patient with AH having hereditary load were younger (58.9 +/- 0.75 and 61.3 +/- 0.89 years, respectively, p=0.017) and had significantly lower age of debut of the disease (44.4 +/- 0.84 and 47.5 +/- 1.03 years, respectively; p=0.013), higher values of systolic (204.8 +/- 7.66 and 187.0 +/- 2.04 mm Hg; p=0.032) and diastolic (111.2 +/- 1.05 and 107.3 +/- 1.17 mm Hg, respectively; p=0.025) arterial pressure (AP) compared with patients with AH without hereditary loaded anamnesis. Portion of patients with 3 degree of severity of AH was higher among patients with "familial" AH (53.6 and 44.1%, respectively, p=0.018). Early debut (in the age younger than 45 years in men and 55 years in women) was associated with carriage of genotype TT of polymorphic marker C825 of GNB3 gene (OR 2.65 95CI [1.27-5.54], p=0.005) and genotype AA of polymorphic marker A(A153)G of AT2R1 gene (OR 1.67 95% CI [1.03-2.77], p=0.024). Higher AP level corresponding to 3-rd degree AH in the group of patients with burdened familial anamnesis was associated with carriage of Asn allele of polymorphic marker Lysl98Asn of EDN1 gene (OR 2.24 95% CI [1.20-4.18], p=0.008), 4a allele of polymorphic marker 4a/4b of NOS3 gene (OR 2.23 C/[1.29-3.83], p=0.002), genotype ArgArg of polymorphic marker Glnl92Arg of PON1 gene (OR 6.14 C7[1.46-25.67], p=0.01), T allele of polymorphic marker of C825T gene GNB3 (OR 1.75 C/[1.11-2.76], p=0.01) and genotype AA of polymorphic marker A(A153)G of AT2R1 gene (OR 2.61 C/11.29-5.34], p=0.005). In patients without burdened familial anamnesis 3-rd degree AH was associated with higher frequency of allele Ala of polymorphic marker Pro12A1a of PPARG2 gene.
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PMID:[Association of genetic factors with clinical peculiarities of hypertensive disease in patients with burdened familial anamnesis]. 1925 15

Although hypertension has been recognized as a risk factor for chronic kidney disease (CKD), the genetic factors for predisposition to CKD in individuals with hypertension remain largely unknown. The purpose of this study was to identify the genetic variants that confer susceptibility to CKD among individuals with hypertension. The study population comprised 3696 Japanese individuals with hypertension (2265 men, 1431 women), including 1257 individuals (789 men, 468 women) with CKD (estimated glomerular filtration rate (eGFR) <60 ml min(-1) per 1.73 m(2)) and 2439 controls (1476 men, 963 women; eGFR >or=60 ml min(-1) per 1.73 m(2)). The genotypes for 30 polymorphisms of 26 candidate genes were determined. An initial screening of allele frequencies by the chi(2)-test revealed that eight polymorphisms were significantly (false discovery rate <0.05) associated with the prevalence of CKD in hypertensive individuals. Subsequent multivariable logistic regression analysis with adjustment for covariates as well as a stepwise forward selection procedure revealed that the T --> C (Val591Ala) polymorphism of APOB (rs679899), the -681C --> G polymorphism of PPARG (rs10865710), the T --> C (Cys1367Arg) polymorphism of WRN (rs1346044), the -850C --> T polymorphism of TNF (rs1799724), the -219G --> T polymorphism of APOE (rs405509), the C --> T polymorphism of PTGS1 (rs883484) and the 41A --> G (Glu14Gly) polymorphism of ACAT2 (rs9658625) were significantly (P<0.05) associated with the prevalence of CKD. Our results suggest that APOB, WRN, ACAT2, APOE, PPARG, TNF and PTGS1 are susceptibility loci for CKD among Japanese individuals with hypertension. Determination of the genotypes for these polymorphisms may prove informative for the assessment of genetic risk for CKD among such individuals.
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PMID:Association of candidate gene polymorphisms with chronic kidney disease in Japanese individuals with hypertension. 1928 63

We evaluated genetic variants of apolipoprotein E (APOE HhaI) and their association with serum lipids in colorectal cancer (CRC), together with eating habits and personal history. Eight-seven adults with CRC and 73 controls were studied. APOE*2 (rs7412) and APOE*4 (rs429358) were identified by polymerase chain reaction-restriction fragment length polymorphism. APOE gene polymorphisms were similar in both groups, but the epsilon4/epsilon4 genotype (6%) was present only in controls. The patients had reduced levels (mean +/- SD) of total cholesterol and low-density lipoprotein cholesterol fraction (180.4 +/- 49.5 and 116.1 +/- 43.1 mg/dL, respectively) compared to controls (204.2 +/- 55.6, P = 0.135 and 134.7 +/- 50.8 mg/dL; P = 0.330, respectively) indicating that they were not statistically significant after the Bonferroni correction. The APOE*4 allele was associated with lower levels of total cholesterol, low- and high-density lipoprotein cholesterol fraction and increased levels of very low-density lipoprotein cholesterol fraction and triglycerides only among patients (P = 0.014). There was a positive correlation between the altered lipid profile and increased body mass indexes in both groups (P < 0.010). Moreover, a higher rate of hypertension and overweight was observed in controls (P < 0.002). In conclusion, the presence of the epsilon4/epsilon4 genotype only in controls may be due to a protective effect against CRC. Lower lipid profile values among patients, even those on lipid-rich diets associated with the APOE*4 allele, suggest alterations in the lipid synthesis and metabolism pathways in CRC.
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PMID:Association between apolipoprotein E genotype, serum lipids, and colorectal cancer in Brazilian individuals. 1937 87

The purpose of the present study was to identify genetic variants which confer susceptibility to chronic kidney disease (CKD) in high- or low-risk subjects defined by conventional risk factors separately. The study population comprised 2828 Japanese individuals, including 434 subjects with CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)] and 2394 controls (eGFR > or =60 ml/min/ 1.73 m(2)). The 1012 high-risk subjects had both hypertension and diabetes mellitus, and the 1816 low-risk subjects had none of these conditions. The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that ten different polymorphisms were associated (P<0.05) with the prevalence of CKD in high- or low-risk subjects: the -519Aright curved arrow G polymorphism of MMP1, the 1061Aright curved arrow G (Ile405Val) polymorphism of CETP, the Aright curved arrow G (Lys45Glu) polymorphism of MMP3, the -219Gright curved arrow T polymorphism of APOE, the Aright curved arrow G (Ile1205Val) polymorphism of COL3A1, the -863Cright curved arrow A polymorphism of TNF, and the 1454Cright curved arrow G (Leu125Val) polymorphism of PECAM1 in high-risk subjects; and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2, the 2386Aright curved arrow G (Ile796Val) polymorphism of SCAP, and the TAAAright curved arrow del polymorphism of PDE4D in low-risk subjects. Among these polymorphisms, the -519Aright curved arrow G polymorphism of MMP1 and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2 were most significantly associated with CKD in high- or low-risk individuals, respectively. These results suggest that polymorphisms associated with CKD may differ among high- or low-risk subjects. Stratification of subjects according to conventional risk factors may thus be important for personalized prevention of CKD based on genetic information.
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PMID:Association of gene polymorphisms with chronic kidney disease in high- or low-risk subjects defined by conventional risk factors. 1942 5

We examined the impact of hypertension on cerebrospinal fluid (CSF) biomarkers amyloid-beta1-42 (Abeta42), total tau (tau), and phosphorylated tau at threonine 181 (ptau-181), and assessed the modifying role of APOE genotype in this relation in 546 patients (mean age 65 +/- 10, 47% female) from our memory-clinic. Of these patients 150 had subjective complaints, 140 were diagnosed with mild cognitive impairment, and 256 with Alzheimer's disease. Linear regression analyses adjusted for age, gender, and diagnosis showed that the association of hypertension with tau and ptau-181 was modified by APOE genotype (p-values for interaction p< 0.05). In APOE epsilon4 homozygotes (n=74), and to a lesser extent in APOE epsilon4 heterozygotes, hypertension was associated with higher tau and ptau-181 levels; beta (95%CI) were 188 (11; 364) pg/mL and 22 (3; 42) pg/mL for the APOE epsilon4 homozygotes. Hypertension was not associated with Abeta42 levels, and APOE genotype did not modify this relation. Our findings suggest that hypertension is directly related to tau pathology in APOE epsilon4 homozygous carriers.
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PMID:Joint effect of hypertension and APOE genotype on CSF biomarkers for Alzheimer's disease. 2041 98

Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study.
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PMID:Gender differences in tea, coffee, and cognitive decline in the elderly: the Cardiovascular Health Study. 2184 Dec 54


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