Mortality and apolipoprotein E in Hispanic, African-American, and Caucasian elders

To investigate whether mortality risk is influenced by apolipoprotein E (APOE) genotype and whether the risk differs by ethnicity, we compared the mortality risk in 2,112 individuals > or = 65 years of age residing in northern Manhattan in New York. Mortality risks associated with the APOE genotype, adjusted for sex, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, differed significantly by ethnic group. Among Caucasian and Hispanics, the E2/E3 genotype was associated with the lowest mortality risk in the multivariate Cox proportional hazards modeling, adjusted for lipid levels, whereas mortality risk did not differ substantially between the E4/E3 and E3/E3 genotypes. Among African-Americans, the E2/E3 genotype was not associated with the lowest mortality risk, but the E4/E3 genotype was. Adjustment for heart disease, diabetes, and stroke reduced mortality risk associated with each genotype by about 50% for all ethnic groups, but the patterns remained the same. Although we cannot rule out the possibility of a healthy survival bias, our analyses designed to examine healthy survival by comparing risk of mortality in groups who were younger or older at entry do not support this possibility. Our findings suggest that the APOE genotype is associated with mortality and that the genotypic risks differ by ethnic group. Nearly 50% of the mortality risk associated with the APOE genotype appears to act through major chronic diseases, but those diseases only partially explain the mechanism by which the genotypic risk acts. To better understand the observed ethnic differences in mortality risk by genotype, a detailed prospective study is needed to examine the relationships among APOE, other candidate genes, health conditions, and eventual death.     

Mortality and Apolipoprotein E in Hispanic,African‐American,and Caucasian elders

To investigate whether mortality risk is influenced by apolipoprotein E (APOE) genotype and whether the risk differs by ethnicity, we compared the mortality risk in 2,112 individuals ≥ 65 years of age residing in northern Manhattan in New York. Mortality risks associated with the APOE genotype, adjusted for sex, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), and triglycerides, differed significantly by ethnic group. Among Caucasian and Hispanics, the E2/E3 genotype was associated with the lowest mortality risk in the multivariate Cox proportional hazards modeling, adjusted for lipid levels, whereas mortality risk did not differ substantially between the E4/E3 and E3/E3 genotypes. Among African‐Americans, the E2/E3 genotype was not associated with the lowest mortality risk, but the E4/E3 genotype was. Adjustment for heart disease, diabetes, and stroke reduced mortality risk associated with each genotype by about 50% for all ethnic groups, but the patterns remained the same. Although we cannot rule out the possibility of a healthy survival bias, our analyses designed to examine healthy survival by comparing risk of mortality in groups who were younger or older at entry do not support this possibility. Our findings suggest that the APOE genotype is associated with mortality and that the genotypic risks differ by ethnic group. Nearly 50% of the mortality risk associated with the APOE genotype appears to act through major chronic diseases, but those diseases only partially explain the mechanism by which the genotypic risk acts. To better understand the observed ethnic differences in mortality risk by genotype, a detailed prospective study is needed to examine the relationships among APOE, other candidate genes, health conditions, and eventual death. © 2001 Wiley‐Liss, Inc.     

APOE-related mortality: effect of dementia, cardiovascular disease and gender

Allele-frequency comparisons between younger and older populations suggest an effect of apolipoprotein E gene (APOE) on mortality, not consistently confirmed by longitudinal data. Our aim was to assess the effect of APOE on survival taking into account the possible contribution of Alzheimer's disease, other dementias, ischemic heart- and cerebrovascular disease (IHCD). In a community-based longitudinal study, the Kungsholmen Project, 75+ year-old individuals (n=1094) were examined, and followed for 18 years. An increased mortality-risk of 22% in those with the epsilon4 allele was detected; whereas a 28% decreased mortality-risk was detected in those with the epsilon2 allele compared to those with the epsilon3epsilon3 genotype. IHCD adjustment did not change the mortality-risk in those with the epsilon4 allele or the epsilon2 allele. Dementia accounted for the majority of the increased mortality-risk associated with the epsilon4 allele, but the protective effect of the epsilon2 allele remained. Both effects of the epsilon4 allele and the epsilon2 allele were strongly modified by gender. A 49% elevated risk for death in men was related to the epsilon4 allele, and a 36% decreased mortality-risk was found in women with the epsilon2 allele. These findings suggest different roles for the APOE alleles in survival by gender in old age.     

Depression and health-related quality of life in ethnic minorities seeking care in general medical settings

BACKGROUND: To examine ethnic groups differences in (a) prevalence of depressive disorders and (b) health related quality of life in fee-for-service and managed care patients (n=21504) seeking care in general medical settings. METHODS: Data are from the Medical Outcomes Study, a multi-site observational study of outpatient practices. The study screened patients of clinicians (family practice, internal medicine, cardiology, diabetology and endocrinology) for four chronic medical conditions; depression, coronary heart disease, hypertension and diabetes. A brief eight-item depression screener followed by the Diagnostic Interview Schedule-Depression Section (DIS) for screener positives identified depressed patients (n=2195). The Short Form Health Survey (SF-36) assessed health-related quality of life. Patient self-report determined ethnicity. RESULTS: Before adjusting for demographic factors, African-Americans and Hispanics had highest rates of depressive symptoms. Asian-Americans had the lowest. After adjusting for demographics (particularly gender and income), we found few statistically significant differences in prevalence or severity of depression. However, among the depressed, Whites were the most, and African-Americans the least likely to report suicidal ideation (p<0. 01), and Hispanics and Whites were more likely to have melancholia (p<0.01). African-Americans reported the poorest quality of life. LIMITATIONS: DSM III criteria (though few changes in DSM IV), and relatively small sample size of Asian-Americans compared to other groups. CONCLUSIONS: Gender and socioeconomic status are more significant factors than ethnicity in determining risk for depressive disorder. However, ethnic differences in symptom presentation, and health-related quality of life could have clinical and social consequences, and merit further study.     

APOE/C1/C4/C2 hepatic control region polymorphism influences plasma apoE and LDL cholesterol levels

We characterized 102 kb of chromosome 19 containing the apolipoprotein (APO) E/C1/C4/C2 cluster and two flanking genes for common DNA variants associated with plasma low-density lipoprotein cholesterol (LDL-C) level. DNA variants were identified by comparing sequences of 48 haploid hybrid cell lines. We genotyped participants (1943 Whites and 2046 African-Americans) of the Coronary Artery Risk Development in Young Adults study for 115 variants. After controlling for the effects of the APOE epsilon2/3/4 polymorphism, a single nucleotide polymorphism, rs35136575, in the downstream hepatic control region 2 (HCR-2) was associated with LDL-C in Caucasians (P = 0.0004), accounting for 1% of variation. We genotyped rs35136575 in the Atherosclerosis Risk in Communities (ARIC) cohort (3679 African-Americans and 10 427 Whites) and in the Genetic Epidemiology Network of Arteriopathy (GENOA) sibships (1381 African-Americans in 592 sibships, 1116 Caucasians in 503 sibships and 1378 Mexican-Americans in 416 sibships), finding association with LDL-C level in ARIC Caucasians (P = 0.0064). Lower plasma LDL-C was observed with the rare allele. Plasma apoE level was strongly associated with HCR-2 variant genotype in all three GENOA samples (P 相似文献   

Apolipoprotein E gene in frontotemporal dementia: an association study and meta-analysis

No definite genetic risk factor of non-monogenic frontotemporal dementia (FTD) has yet been identified. Several groups have examined the potential association of FTD with the apolipoprotein E (APOE) gene, but the results are inconsistent. Our objective was to determine whether APOE is a risk factor of FTD, using the largest series of patients with FTD and controls analysed so far (94 unrelated patients and 392 age and sex-matched controls), and a meta-analysis. Homozygosity for the E2E2 genotype was significantly associated with FTD (odds ratio (OR)=11.3; P=0.033, exact test). After stratification on familial history (FH) for FTD, the OR for E2E2 was still found significant when analysing only patients with a positive FH (OR=23.8; P=0.019). The meta-analysis, using 10 case-control studies with available genotype or allele information, comprising a total of 364 FTD patients and 2671 controls, including the patients of the present study, did not reach statistical significance even if the E2E2 genotype was more frequent in patients than in controls (0.018 vs 0.006, respectively). Because of studies heterogeneity (Mantel-Haenszel statistics: P=0.004), we analysed on one hand the neuropathologically-confirmed studies, and on the other hand the clinical-based studies. In the neuropathologically-confirmed studies (Mantel-Haenszel statistics: P=ns), we found a significant increase of the E2 allele frequency in FTD patients (OR[E2 vs E3]=2.01; 95% CI=1.02-3.98; P=0.04). The same result was found in the clinical-based studies, but studies heterogeneity remained. No result was significant with the E4 allele. The E2 allele seems so to be a risk factor of FTD whereas this allele is associated with the lowest risk in Alzheimer's disease. If this finding was confirmed, it could provide new insights into the mechanisms of differential risk related to APOE in neurodegenerative diseases.     

Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults

The apolipoprotein E genotype (APOE) is an established risk factor for Alzheimer disease, with the age-at-onset occurring earlier in individuals having at least one APOE epsilon 4 allele, relative to the APOE epsilon 3 or APOE epsilon 2 isoforms. Moreover, nondemented older adults with the APOE epsilon 4 allele also show diminished cognitive performance, particularly on tests of learning and memory, and an accelerated decline in memory performance with increasing age. The current investigation extends the study of the APOE epsilon 4 allele and cognitive performance to healthy, middle-aged adults. A community sample of 220 non-Hispanic Caucasian men and women, aged 24-60 (average age = 46), were genotyped for the APOE polymorphism and completed a battery of neuropsychological tests. Multivariate analyses were conducted on measures of verbal learning and memory (e. g., learning a list of words and recalling them 30 min later), visual memory (e.g., reproducing a previously copied figure from memory), and attention span (e.g., repeating long lists of digits), after adjustments for age, and estimated IQ. Results indicated that performance on learning and memory tasks was significantly poorer in adults having any APOE epsilon 4 allele, relative to adults with APOE epsilon 2 and epsilon 3 genotypes (P <.01). Attention span did not differ by genotype. These findings, the first in a sample of middle-aged adults, suggest that the APOE polymorphism is a marker for age-related decline in memory (detectable prior to overt, clinical manifestations of memory loss), and/or a marker for individual differences in memory ability across the life span. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:707-711, 2000.     

Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease

Objectives

Investigate apolipoprotein E ε4 (APOE4) gene and aging effects on florbetapir F18 positron emission tomography (PET) in normal aging and Alzheimer's disease (AD). Methods: Florbetapir F18 PET images were analyzed from 245 participants, 18–92 years of age, from Avid Radiopharmaceutical's multicenter registered trials, including 86 younger healthy control volunteers (yHC), 61 older healthy control volunteers (oHC), 53 mild cognitive impairment (MCI) patients, and 45 AD dementia patients (DAT). Mean florbetapir standard uptake value ratios (SUVRs) were used to evaluate the effects of APOE4 carrier status, older age, and their interaction in each of these groups. Results: In comparison with non-carriers, the APOE4 carriers in each of the oHC, MCI, and DAT groups had higher mean cortical-to-cerebellar florbetapir SUVRs, patterns of florbetapir PET elevations characteristic of DAT, and a higher proportion meeting florbetapir PET positivity criteria. Only the oHC group had a significant association between mean cortical florbetapir SUVRs and age. In cognitively normal adults, without regards to APOE4 genotype, amyloid began to increase at age 58 (95% confidence interval [CI]: 52.3–63.7), with a predicted typical age of florbetapir positivity occurring around age 71 years. Presence of the APOE4 gene reduced the age of predicted florbetapir positivity in normal aging to around age 56 years, approximately 20 years younger than non-carriers. Interpretation: Cerebral amyloid deposition is associated with APOE4 carrier status in older healthy control subjects and symptomatic AD patients, and increases with age in older cognitively normal individuals. Amyloid imaging positivity appears to begin near age 56 years in cognitively intact APOE4 carriers and age 76 years in APOE4 non-carriers.     

Lipid metabolism parameters in patients with Alzheimer's disease and their first degree relatives

Recently, it was suggested that the presence of total cholesterol (TC), age and sex interaction in Alzheimer's type dementia (AD) is linked with the apolipoprotein E (APOE) genotype. Our objective was to determine whether the serum lipid profile in AD patients and their first degree non-demented relatives of a certain age (NDR) was dependent on APOE genotype. We included 28 mild to moderate AD and 30 NDR according to DSM-III-R and NINCDS-ADRDA criteria. NDR individuals were investigated in an age group similar to the AD group (brother-sister relationship) and in a group including younger individuals (AD patients-children relationship). Our data indicate significant differences between decreased total cholesterol and low density lipoprotein cholesterol ratio in the group of AD patients versus NDR individuals of similar age, independent of APOE genotype, and an increased total cholesterol and low density lipoprotein cholesterol ratio in a group of AD patients versus their children of the same genotype. There was no significant correlation between triglycerides and high density lipoprotein levels with APOE genotype in any of the tested groups. In conclusion, there was a decreased selected lipid serum profile parameters in AD compared to age matched non demented first degree relatives.     

Apolipoprotein E polymorphism and its relation to plasma lipids in coronary heart disease

Background : The present investigation is aimed at examining the Apolipoprotein E (APOE) genotypic influence on coronary heart disease (CHD) risk in northwest India (Punjab), where this disease is emerging as a major threat to public-health care system. Materials and Methods: The present study comprised of angiographically diagnosed coronary heart disease patients (n = 193) and controls (n = 150) of Punjab. Genetic polymorphism of APOE gene was investigated by polymerase chain reaction (PCR), and its association with lipid levels was evaluated. Results : The allele frequencies of epsilon2, epsilon3, and epsilon4 were 0.054, 0.795, 0.151; and 0.077, 0.856, 0.067 in patients and controls respectively. The bearers of E3/E4 genotype had threefold higher propensity of developing CHD in this population (OR, 3.04; CI, 1.55-6.25; P P P Conclusions : A significant association (P = 0.016) of epsilon4 allele, especially E3/E4 genotype, with CHD was observed, along with HDL-C and LDL-C concentrations, in the population of northwest India.     

Hispanic-white MMPI comparisons: Does psychiatric diagnosis make a difference?

Recent research on Blacks or African-Americans in psychiatric settings suggests that Black-White MMPI differences are minimized or eliminated when researchers match or control for key moderator variables, including psychiatric diagnosis. This study attempted to determine whether Hispanic- White MMPI differences are either minimized or eliminated when Hispanics and Whites are matched on three key moderator variables —age, education, and psychiatric diagnosis. Results suggest that even after controlling for these variables, MMPI differences between Hispanics and Whites are evident. Recommendations for culturally sensitive Hispanic MMPI research are presented.     

Specifying race-ethnic differences in risk for psychiatric disorder in a USA national sample

BACKGROUND: Epidemiological studies have found lower than expected prevalence of psychiatric disorders among disadvantaged race-ethnic minority groups in the USA. Recent research shows that this is due entirely to reduced lifetime risk of disorders, as opposed to persistence. Specification of race-ethnic differences with respect to clinical and social characteristics can help identify the protective factors that lead to lower lifetime risk among disadvantaged minority groups. METHOD: Data on 5424 Hispanics, non-Hispanic Blacks, and non-Hispanic Whites came from the National Comorbidity Survey Replication, a nationally representative survey conducted with the World Mental Health version of the Composite International Diagnostic Interview. Race-ethnic differences in risk of disorders were compared across specific diagnoses, ages of onset, cohorts and levels of education. RESULTS: Both minority groups had lower risk for common internalizing disorders: depression, generalized anxiety disorder, and social phobia. In addition, Hispanics had lower risk for dysthymia, oppositional-defiant disorder and attention deficit hyperactivity disorder; non-Hispanic Blacks had lower risk for panic disorder, substance use disorders and early-onset impulse control disorders. Lower risk among Hispanics, relative to non-Hispanic Whites, was found only among the younger cohort (age相似文献   

Butyrylcholinesterase K variant is genetically associated with late onset Alzheimer's disease in Northern Ireland

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has been associated, sometimes controversially, with polymorphisms in a number of genes. Recently the butyrylcholinesterase K variant (BCHE K) allele has been shown to act in synergy with the apolipoprotein E epsilon4 (APOE epsilon4) allele to promote risk for AD. Most subsequent replicative studies have been unable to confirm these findings. We have conducted a case-control association study using a clinically well defined group of late onset AD patients (n=175) and age and sex matched control subjects (n=187) from the relatively genetically homogeneous Northern Ireland population to test this association. The BCHE genotypes of patients were found to be significantly different from controls (chi(2)=23.68, df=2, p<0.001). The frequency of the K variant allele was also found to differ significantly in cases compared to controls (chi(2)=16.39, df=1, p<0.001) leading to an increased risk of AD in subjects with this allele (OR=3.50, 95% CI 2. 20-6.07). This risk increased in subjects 75 years and older (OR=5. 50, 95% CI 2.56-11.87). At the same time the APOE epsilon4 associated risk was found to decrease from 6.70 (95% CI 2.40-19.04) in 65-74 year olds to 3.05 (95% CI 1.34-6.95) in those subjects 75 years and older. However, we detected no evidence of synergy between BCHE K and APOE epsilon4. The results from this study suggest that possession of the BCHE K allele constitutes a significant risk for AD in the Northern Ireland population and, furthermore, this risk increases with increasing age.     

Association of APOE epsilon2/epsilon3/epsilon4 and promoter gene variants with dementia but not cardiovascular mortality in old age.

The common apolipoprotein E (APOE) alleles epsilon2, epsilon3, and epsilon4 are associated with the risk of dementia and cardiovascular disease. Recently, two functional variants (- 219G/T and -491A/T) were identified in the promoter of the APOE gene that enable a further characterization of the role of the APOE locus in disease. We investigated the contribution of these APOE gene variants to dementia and cardiovascular mortality in old age using a population-based cohort of 648 subjects aged 85 years and over (Leiden 85-Plus Study). Genotypes containing an APOE epsilon4 allele were associated with a 4.1-fold (95% CI, 2.2-7.7) increased risk of dementia as compared to the epsilon3/epsilon3 genotype in old subjects. Moreover, homozygosity for the -219T allele was found to be associated with a 2.4-fold (95% CI, 1.0-5.8) increased risk independently of epsilon2 and epsilon4; the -491A/T variant was not associated with dementia. Over a 10-year follow-up period, the risk of cardiovascular mortality was not increased among epsilon4 carriers (RR, 0.6; 95% CI, 0.4-1.0) or -219T homozygous subjects (RR, 1.1; 95% CI, 0.7-1.7), nor did it decrease among -491T homozygous subjects (RR, 1.4; 95% CI, 0.6-3.1). In conclusion, both the APOE epsilon2/epsilon3/epsilon4 and the -219G/T variant were identified as risk factors for dementia but not cardiovascular mortality in old age. Our results support the hypothesis that both the isoform and the amount of APOE may influence the risk of dementia. Furthermore, they emphasize that variation at the APOE locus has a higher impact on the risk of dementia than on the risk of cardiovascular disease in old age.     

Gene dose of apolipoprotein E and age-related hearing loss

Next to outer hair cell dysfunction, age-related hearing loss may be explained by apolipoprotein E (APOE) genotype. In the Leiden 85-plus Study, a population-based study, the participants were 85 years old. We measured hearing loss by pure-tone audiometry in 435 participants in relation to APOE. Results demonstrated that those with the APOE-ε4/ε4 genotype had the highest levels of hearing loss (n = 6; 56.1 dB), those with the APOE-ε3/ε4 or ε2/ε4 genotype (n = 89) had intermediate levels of hearing loss (51.0 dB), and those without the APOE-ε4 allele (n = 340) had the lowest levels of hearing loss (48.9 dB), p for trend = 0.02. Eighty percent of participants had hearing loss of 35 dB and more, that is, hearing impairment. The APOE-ε4 allele was associated with a 2.0-fold increased risk of hearing impairment (confidence interval [CI 95%], 1.0-4.0), compared with those without the APOE-ε4 allele. The risk for hearing impairment in subjects with the APOE-ε4 allele remained similar after adjustment for cardiovascular disease, stroke, and cognitive impairment. Our results suggest that the APOE-ε4 allele contributes to age-related hearing loss.     

Ethnic variation in AMD-associated complement factor H polymorphism p.Tyr402His

Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in the developed world. Previous studies have demonstrated that the c.1204T>C, p.Tyr402His allelic variant in the complement factor H (CFH) gene is associated with an approximately three-fold increased risk for AMD in Caucasians of predominantly European descent. Both the prevalence as well as the phenotypic spectrum of AMD varies widely among persons of different ethnicities. We hypothesized that populations with a lower prevalence of AMD might also have a lower prevalence of the CFH risk allele. In this study we sought to determine the frequency of this sequence variant in control populations of Caucasians, African Americans, Hispanics, Somalis, and Japanese. Normal control populations were assembled for each ethnic group: Caucasian (n=148), Somali (n=128), African American (n=75), Hispanic (n=81), and Japanese (n=82). Individuals were genotyped using a restriction digest assay and the frequency of the C allele at nucleotide position 1204 of the CFH gene was determined. A bioinformatic approach was used to identify SNPs in linkage disequilibrium with rs1061170 (c.1204T>C, p.Tyr402His) from the human haplotype map project database (HapMap) in order to validate the findings. We found widely discordant frequencies of the risk allele between some of the different ethnic groups: Japanese 0.07+/-0.02, Hispanics 0.17+/-0.03, African-Americans 0.35+/-0.04, Caucasians 0.34+/-0.03, and Somalis 0.34+/-0.03. Allele frequencies generated by analysis of the HapMap database were consistent with these findings. This study suggests that there are other yet unidentified genetic factors important in the pathogenesis of AMD that may mitigate the effects of c.1204T>C, p.Tyr402His variant.     

Apolipoprotein E and α-1-antichymotrypsin allele polymorphism in sporadic and familial Alzheimer's disease

Alzheimer disease (AD) patients with both sporadic and familial forms of AD and non-demented controls were genotyped for common polymorphisms in the signal peptide for α-1-antichymotrypsin (ACT) gene and in two different regions of apolipoprotein E (APOE) gene. The ACT TT genotype was over-represented (P=0.025) in patients with early onset of sporadic AD. In this patient's group ACT TT genotype conferred a significant crude odds ratio for the disease (OR=2.09; 95% CI=1.09–4.00, P=0.025). After adjustment for the APOE ε4 and APOE −491 genotypes, logistic regression analysis confirmed that the ACT TT genotype resulted independently associated with early onset AD (adjusted OR=2.56; 85% C.I.=1.3–5.2, P=0.009). The frequency of APOE ε4 allele was increased in AD, as expected (OR=5.92, 95% CI=3.60–9.70, P=0.0001). On the contrary, the APOE −491 A/T genotypes were not associated with AD. No preferential association of the APOE ε4 allele or APOE −491 A/T genotypes with ACT A/T alleles was observed in AD. Present findings indicated that subjects with ACT TT genotype had an increased risk of developing AD and suggested that this genotype influenced the risk of an early onset of the disease by affecting the production of ACT molecules.     

Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age-matched controls

Alzheimer disease (AD) is an emotionally devastating and exceptionally costly disease. Apolipoprotein E (APOE) is a major risk factor gene for AD regardless of age of onset or family history. However, this association may not be as strong or consistent in ethnic groups such as African Americans, raising the possibility of other modifier gene(s). In a group of African American AD patients, a significantly increased risk of AD was associated with two E4 alleles (OR = 5.6; 95% CI = 1.5-21.0) or one E4 allele (OR = 2.5; 95% CI = 1.3-5.0) when compared to E3/E3 genotype, and there was a significant lowering of age of onset for affecteds with E4/E4 genotype as compared to one E2 allele (P = 0.02) or all others (P = 0.03). We also found a significant increase in age of onset with the -308 #2 (A) allele of TNF when compared to AD cases with no #2 allele. A significant increase in age was also demonstrated with the #2 allele (99 base pairs) of the microsatellite TNFa, located approximately 10.5 kb upstream of TNF. When these two alleles were combined with the TNF -238G (#1) allele to give a haplotype, the significant increase in age was still demonstrated. Polymorphisms in the APOE promoter and six other candidate genes did not appear to demonstrate any significant association with our African American AD patients. Our results confirm the established association of APOE4 to AD observed in several ethnic groups, including African Americans. In addition, TNF appears to have some modifying effect in AD, primarily on age of onset, or it could be in linkage disequilibrium with a modifier locus nearby.     

Effect of the APOE‐491A/T promoter polymorphism on apolipoprotein E levels and risk of Alzheimer disease: The Rotterdam Study

The apolipoprotein E (APOE) gene is involved in lipid transport. A common polymorphism in this gene with the APOE*2, APOE*3, and APOE*4 alleles influences plasma levels of apolipoprotein E and cholesterol. Besides its role in lipid transport, the APOE*4 allele is a genetic risk factor for Alzheimer disease (AD). Recently, a polymorphism in the APOE promoter region was found to be involved in plasma apolipoprotein E levels and was found associated with AD. We studied the effect of this ?491A/T promoter polymorphism on plasma apolipoprotein E levels and risk for AD in a population‐based case‐control study. We found that there was a modest but statistically significant effect of the ?491A/T polymorphism on plasma apolipoprotein E levels independent of the APOE genotype. The lowest plasma levels were measured for the AA genotype, highest levels for the TT genotype, and intermediate levels for the heterozygotes. There was a small effect of the ?491 AA genotype on AD risk that disappeared after adjusting for APOE genotypes. Our data suggest that the ?491A/T polymorphism has an APOE genotype‐independent effect on plasma apolipoprotein E levels but no APOE‐independent effect on AD risk. © 2002 Wiley‐Liss, Inc.     

Effect of the APOE-491A/T promoter polymorphism on apolipoprotein E levels and risk of Alzheimer disease: The Rotterdam Study

The apolipoprotein E (APOE) gene is involved in lipid transport. A common polymorphism in this gene with the APOE*2, APOE*3, and APOE*4 alleles influences plasma levels of apolipoprotein E and cholesterol. Besides its role in lipid transport, the APOE*4 allele is a genetic risk factor for Alzheimer disease (AD). Recently, a polymorphism in the APOE promoter region was found to be involved in plasma apolipoprotein E levels and was found associated with AD. We studied the effect of this -491A/T promoter polymorphism on plasma apolipoprotein E levels and risk for AD in a population-based case-control study. We found that there was a modest but statistically significant effect of the -491A/T polymorphism on plasma apolipoprotein E levels independent of the APOE genotype. The lowest plasma levels were measured for the AA genotype, highest levels for the TT genotype, and intermediate levels for the heterozygotes. There was a small effect of the -491 AA genotype on AD risk that disappeared after adjusting for APOE genotypes. Our data suggest that the -491A/T polymorphism has an APOE genotype-independent effect on plasma apolipoprotein E levels but no APOE-independent effect on AD risk.