Apolipoprotein E genotype and cognitive dysfunction after noncardiac surgery

BACKGROUND: Apolipoprotein E is important in recovery after neuronal damage. The epsilon4 allele of the apolipoprotein E gene has been shown as a risk factor for Alzheimer disease, poor outcome after cerebral injury, and accelerated cognitive decline with normal aging. The authors hypothesized that patients with the epsilon4 allele would have an increased risk of postoperative cognitive dysfunction (POCD) after noncardiac surgery. METHODS: In a multicenter study, a total of 976 patients aged 40 yr and older undergoing noncardiac surgery were tested preoperatively and 1 week and 3 months after surgery with a neuropsychological test battery comprising seven subtests. POCD was defined as a decline in test performance of more than 2 SD from the expected. Apolipoprotein E genotypes were determined by blood sample analysis at a central laboratory. Multivariate logistic regression analysis with POCD as the dependent variable assessed presence of the epsilon4 allele (yes/no) and other possible risk factors. RESULTS: The epsilon4 allele was found in 272 patients. One week after surgery, the incidence of POCD was 11.7% in patients with the epsilon4 allele and 9.9% in patients without the epsilon4 allele (P = 0.41). Three months later, POCD was found in 10.3% of patients with the epsilon4 allele and in 8.4% of patients without the epsilon4 allele (P = 0.40). Multivariate logistic regression analysis did not identify the epsilon4 allele as a risk factor at 1 week (P = 0.33) or 3 months (P = 0.57). CONCLUSIONS: The authors were unable to show a significant association between apolipoprotein E genotype and POCD, but statistical power was limited because of a lower incidence of POCD than expected.     

Apolipoprotein E Genotype and Cognitive Dysfunction after Noncardiac Surgery

Background: Apolipoprotein E is important in recovery after neuronal damage. The [epsilon]4 allele of the apolipoprotein E gene has been shown as a risk factor for Alzheimer disease, poor outcome after cerebral injury, and accelerated cognitive decline with normal aging. The authors hypothesized that patients with the [epsilon]4 allele would have an increased risk of postoperative cognitive dysfunction (POCD) after noncardiac surgery.

Methods: In a multicenter study, a total of 976 patients aged 40 yr and older undergoing noncardiac surgery were tested preoperatively and 1 week and 3 months after surgery with a neuropsychological test battery comprising seven subtests. POCD was defined as a decline in test performance of more than 2 SD from the expected. Apolipoprotein E genotypes were determined by blood sample analysis at a central laboratory. Multivariate logistic regression analysis with POCD as the dependent variable assessed presence of the [epsilon]4 allele (yes/no) and other possible risk factors.

Results: The [epsilon]4 allele was found in 272 patients. One week after surgery, the incidence of POCD was 11.7% in patients with the [epsilon]4 allele and 9.9% in patients without the [epsilon]4 allele (P = 0.41). Three months later, POCD was found in 10.3% of patients with the [epsilon]4 allele and in 8.4% of patients without the [epsilon]4 allele (P = 0.40). Multivariate logistic regression analysis did not identify the [epsilon]4 allele as a risk factor at 1 week (P = 0.33) or 3 months (P = 0.57).     

Apolipoprotein E epsilon4 allele and neurobehavioral status after on-pump coronary artery bypass grafting

Abstract Background and Aim: The presence of apolipoprotein E epsilon4 allele is being considered as a risk factor for cognitive decline after cardiac surgery. We sought the effect of apolipoprotein E epsilon4 allele on neurobehavioral status after on-pump coronary artery bypass grafting. Methods: Prior to the operation, neurologic examination and neurobehavioral cognitive status test (COGNISTAT) were performed. Both procedures were repeated on the day of discharge and 3 months after surgery. Apolipoprotein E epsilon4 allele positive and apolipoprotein E epsilon4 allele negative patients' performance on COGNISTAT were compared. Results: There was no statistically significant demographic and operative data difference between two groups. No neurological impairment was observed on examinations. There was no statistically significant neurocognitive decline difference between two groups' postoperative performances. Conclusions: It seems that apolipoprotein E epsilon4 allele may not affect neurobehavioral status in the intermediate period after on-pump coronary artery bypass grafting.     

Increased prevalence of apolipoprotein E3/E4 genotype among Swedish renal transplant recipients.

There is increasing evidence that lipoproteins are involved in the progression of kidney diseases and in the deterioration of kidney transplant function, although the exact mechanism is still not known. Common polymorphisms of apolipoprotein E genotype associate with the variability of lipoprotein levels and composition. We have, therefore, determined the apolipoprotein E genotype in a group of 112 renal transplant patients, of whom 27 had had an episode of acute vascular rejection, while 85 had not. We found no difference in apolipoprotein E genotype distribution or in relative allele frequency in the vascular rejection group as compared with the group without vascular rejection. The apolipoprotein E genotype distribution in the transplant group was also compared with that in a group of 407 healthy Swedish individuals. The E3/E4 genotype occurred with a significantly increased frequency in the transplant group: 38.3 versus 16% in the control group (p < 0.001). The prevalence of individuals carrying the epsilon4 allele among the transplant group was also significantly higher (44%) as compared with the control group (30%; p < 0.01). This increase was entirely due to the predominant increase of E3/E4, as the E4/E4 genotype was less frequent in transplant recipients than in normal controls (3.5 vs. 10.6%; p < 0.05). The relative frequencies of epsilon2 (0.044), epsilon3 (0.716), and epsilon4 (0.238) alleles in the renal transplant group were not different from those of normal controls (0. 078, 0.718, and 0.202, respectively). With regard to the prevalence of E4/E4 in the two groups, the lack of difference in the relative frequency of the epsilon4 allele must be interpreted with caution. The results thus suggest that the E3/E4 genotype may be associated with the progression of kidney disease leading to renal insufficiency. However, the apolipoprotein E genotype does not seem to influence the risk of vascular rejection among transplant recipients.     

Increased frequency of apolipoprotein epsilon 4 allele in type II diabetes with hypercholesterolemia

The apolipoprotein E (apoE) phenotype and allele frequencies were examined in type II (non-insulin-dependent) diabetic patients with normolipidemia (n = 134) and hypercholesterolemia (type IIa hyperlipoproteinemia, n = 35; type IIb hyperlipoproteinemia, n = 42). The frequencies of apoE4-present phenotypes (apoE4/3, apoE4/4, and apoE4/2) were highest in the type IIa group (51.4%), followed by the type IIb group (38.1%) and the normolipidemic group (16.4%), respectively, whereas the frequency of the most common phenotype, apoE3/3, was lowest in the type IIa group (48.6%), followed by the type IIb group (61.9%) and the normolipidemic group (79.9%), respectively. There were significant differences in the apoE phenotype frequencies between the normolipidemic group and the type IIa and IIb groups. The frequency of the epsilon 4 allele was significantly higher in the type IIa (28.6%) and IIb (20.2%) groups than in the normolipidemic group (8.9%), whereas the frequency of the epsilon 3 allele was significantly lower in the type IIa (71.4%) and IIb (78.6%) groups than in the normolipidemic group (89.2%). The frequency of the epsilon 2 allele tended to be lower in diabetic patients with hypercholesterolemia. In addition, these frequencies were also examined in nondiabetic subjects (n = 59). The frequency of the epsilon 4 allele tended to be higher in hypercholesterolemic diabetic subjects (24.1%) than in hypercholesterolemic nondiabetic subjects (15.3%). These data suggest that diabetic patients with the epsilon 4 allele may be more susceptible to hypercholesterolemia than diabetic patients without the epsilon 4 allele and possibly nondiabetic subjects with the epsilon 4 allele, although the underlying mechanism is unknown.     

APOE polymorphisms and the development of diabetic nephropathy in type 1 diabetes: results of case-control and family-based studies

The goal of this study was to examine the association between known polymorphisms in the apolipoprotein E gene (APOE) and diabetic nephropathy (DN) in type 1 diabetes. We used both a case-control comparison and a family-based study design known as the transmission/disequilibrium test (TDT). For the case-control comparison, we collected DNA from 223 subjects with clinically diagnosed DN and 196 control subjects with normoalbuminuria and long-duration type 1 diabetes (> or = 15 years). For the family-based study, we obtained DNA from both parents of 154 DN subjects and 81 control subjects. The frequency of the epsilon2 allele of exon 4 of APOE was significantly higher in DN subjects than in control subjects. The risk of DN was 3.1 times higher (95% CI 1.6-5.9) in carriers of this allele than in noncarriers. In the family study, heterozygous parents for the E2 allele preferentially transmitted epsilon2 to DN offspring (64 vs. 36%, P < 0.03). Four additional polymorphisms (i.e., -491 A/T, -219 G/T, IE1 G/C, and APOCI insertion/deletion [I/D]) that flank the APOE locus were not associated with DN in either the case-control comparison or in the family-based study. In conclusion, the results of the case-control as well as the family-based study provide evidence that the epsilon2 allele of APOE increases the risk of DN in type 1 diabetes. The molecular mechanisms underlying this risk are unclear at present.     

Preliminary report on the association of apolipoprotein E polymorphisms, with postoperative peak serum creatinine concentrations in cardiac surgical patients

BACKGROUND: Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated with major increases in morbidity, mortality, and cost. Genetic polymorphisms have been implicated as a factor in the progression of chronic renal disease, but a genetic basis for the development of acute renal impairment has not been investigated. The authors therefore tested the hypothesis that apolipoprotein E alleles are associated with different postoperative changes in serum creatinine after cardiac surgery. METHODS: The authors performed a prospective observational study with use of data from 564 coronary bypass surgical patients who were enrolled in an ongoing investigation of apolipoprotein E genotypes and organ dysfunction at a university hospital between 1989-1999. Renal function was assessed among apolipoprotein E genotype groups by comparisons of preoperative (CrPre), peak in-hospital postoperative (CrMax) and perioperative change (DCr) in serum creatinine values. RESULTS: The epsilon4 allele grouping (E2 = 2/2,2/3,2/4; E3 = 3/3; E4 = 3/4,4/4) was associated with a smaller increase in postoperative serum creatinine (perioperative change: E4, +0.17; E3, +0.26; E4, +0.27 mg/dl) and a lower peak postoperative creatinine than the epsilon2 and epsilon3 in univariate and multivariate analysis (peak in-hospital postoperative serum creatinine multivariate P = 0.015 vs. epsilon3, P = 0.038 vs. epsilon2). There was no difference in baseline creatinine among allele groups. CONCLUSIONS: Inheritance of the apolipoprotein epsilon4 allele is associated with reduced postoperative increase in serum creatinine after cardiac surgery, compared with the epsilon3 or epsilon2 allele. This is the first report of a possible genetic basis for acute renal impairment. These data may contribute to renal risk stratification for cardiac surgery and raise questions regarding apolipoprotein E and the pathophysiology of acute renal injury.     

Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery

BACKGROUND: There has been increasing recognition of adverse neurodevelopmental sequelae in some children after repair of congenital heart defects. Even among children with the same cardiac defect, significant interindividual variation exists in developmental outcome. Polymorphisms of apolipoprotein E have been identified as a risk factor for worse neurologic recovery after central nervous system injury. METHODS: A single-institution prospective study of patients 相似文献   

Apolipoprotein E polymorphism in 385 patients on renal replacement therapy in Sweden

OBJECTIVE: To examine apolipoprotein (apo) E polymorphism and its possible link to kidney disease in all patients receiving renal replacement therapy in our region. MATERIAL AND METHODS: The apo E genotype, plasma (P) lipids, blood pressure and albumin excretion rate were determined retrospectively in 385 patients. RESULTS: No differences in apo E genotype or the allelic frequencies of epsilon2, epsilon3 or epsilon4 were found between the patient group and a control group of 343 healthy individuals. The apo E3/E4 genotype, however, was found in only 1/24 patients with non-insulin-dependent diabetes mellitus (NIDDM), a significantly lower frequency than that seen in the rest of the patient group (p = 0.041). Similarly, the apo E4/E4 genotype was absent in patients with glomerulonephritis (GN) (p = 0.027). The relative frequency of the epsilon4 allele in patients with GN (0.116) was significantly lower than that in the rest of the patients (0.193; p < 0.05) and that in the control group (0.186; p = 0.027). Furthermore, 19/47 patients (40.4%) with autosomal dominant polycystic kidney disease (ADPKD) had the E3/E4 genotype, as compared to 77/338 (22.8%) in the rest of the patient group (p = 0.035; odds ratio 2.07; CI 1.09-3.92). An increase in the relative frequency of the epsilon4 allele was seen in the same diagnostic group: 0.29 vs 0.16 in the rest of the patient group (p = 0.0023). The mean P-cholesterol level in patients with the epsilon4 allele was 5.9 +/- 1.0 mmol/l, compared to 5.0 +/- 1.1 mmol/l in patients without the epsilon4 allele (p = 0.026). CONCLUSIONS: In this study, variations in the frequencies of the apo epsilon4 allele and the apo E3/E4 and E4/E4 genotypes were found in patients with NIDDM, GN and ADPKD. This result may be a consequence of the effects of the apo epsilon4 and epsilon2 alleles on P-cholesterol and remnant lipoprotein levels. The decreased frequency of apo E3/E4 found in patients with NIDDM may be explained by the fact that the epsilon4 allele gives renoprotection against diabetic nephropathy by lowering plasma remnant lipoprotein levels. Conversely, there may be an association between the apo E3/E4 genotype and the epsilon4 allele in patients with ADPKD, due to the effect of the epsilon4 allele in elevating P-cholesterol levels. The most plausible explanation for the absence of the apo E4/E4 genotype and the lower prevalence of the epsilon4 allele in patients with GN, which is known to result in a higher P-cholesterol compared to the epsilon2 and epsilon3 alleles, ought to be an increase in cardiovascular morbidity, which is known to be associated with a higher P-cholesterol level.     

Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study

Type 2 diabetes may be a risk factor for dementia, but the associated pathological mechanisms remains unclear. We evaluated the association of diabetes alone or combined with the apolipoprotein E (APOE) gene with incident dementia and neuropathological outcomes in a population-based cohort of 2,574 Japanese-American men enrolled in the Honolulu-Asia Aging Study, including 216 subjects who underwent autopsy. Type 2 diabetes was ascertained by interview and direct glucose testing. Dementia was assessed in 1991 and 1994 by clinical examination and magnetic resonance imaging and was diagnosed according to international guidelines. Logistic regression was used to assess the RR of developing dementia, and log-linear regression was used to estimate the incident rate ratio (IRR) of neuropathological outcomes. Diabetes was associated with total dementia (RR 1.5 [95% CI 1.01-2.2]), Alzheimer's disease (AD; 1.8 [1.1-2.9]), and vascular dementia (VsD; 2.3 [1.1-5.0]). Individuals with both type 2 diabetes and the APOE epsilon4 allele had an RR of 5.5 (CI 2.2-13.7) for AD compared with those with neither risk factor. Participants with type 2 diabetes and the epsilon4 allele had a higher number of hippocampal neuritic plaques (IRR 3.0 [CI 1.2-7.3]) and neurofibrillary tangles in the cortex (IRR 3.5 [1.6-7.5]) and hippocampus (IRR 2.5 [1.5-3.7]), and they had a higher risk of cerebral amyloid angiopathy (RR 6.6, 1.5-29.6). Type 2 diabetes is a risk factor for AD and VsD. The association between diabetes and AD is particularly strong among carriers of the APOE epsilon4 allele. The neuropathological data are consistent with the clinical results.     

Better memory and neural efficiency in young apolipoprotein E epsilon4 carriers

The apolipoprotein E (APOE) epsilon4 allele is the major genetic risk factor for Alzheimer's disease, but an APOE effect on memory performance and memory-related neurophysiology in young, healthy subjects is unknown. We found an association of APOE epsilon4 with better episodic memory compared with APOE epsilon2 and epsilon3 in 340 young, healthy persons. Neuroimaging was performed in a subset of 34 memory-matched individuals to study genetic effects on memory-related brain activity independently of differential performance. E4 carriers decreased brain activity over 3 learning runs, whereas epsilon2 and epsilon3 carriers increased activity. This smaller neural investment of epsilon4 carriers into learning reappeared during retrieval: epsilon4 carriers exhibited reduced retrieval-related activity with equal retrieval performance. APOE isoforms had no differential effects on cognitive measures other than memory, brain volumes, and brain activity related to working memory. We suggest that APOE epsilon4 is associated with good episodic memory and an economic use of memory-related neural resources in young, healthy humans.     

Apolipoprotein E4 reduces risk of diabetic nephropathy in patients with NIDDM

Hypercholesterolemia is a major determinant of the decline of renal function in patients with diabetes. Apolipoprotein E polymorphism may influence the metabolism of lipoprotein in diabetic patients. The purpose of this study was to investigate the association between genetic polymorphisms in apolipoprotein E and the progression of diabetic nephropathy in patients with non-insulin-dependent diabetes mellitus over a 10-year period (13 to 37 years; median, 20 years). Subjects with a stable renal function without overt proteinuria had a higher cholesterol level, lower incidences of hypertension and proliferative diabetic retinopathy, and a higher frequency of the E4 allele than subjects with a decline in renal function (end-stage renal failure requiring dialysis treatment). In the diabetic patients, the apolipoprotein E4 carriers had a higher cholesterol level than did the noncarriers. The survival rate from renal disease in the apolipoprotein E4 carriers was higher than in the noncarriers among the diabetic patients. Apolipoprotein E polymorphism and hypertension were identified as independent risk factors for the progression to renal failure. Results indicate that apolipoprotein E polymorphism is associated with the progression of diabetic nephropathy. Presence of the apolipoprotein E4 allele is a protective factor, and other alleles are risk factors.     

Lack of association between the apolipoprotein E gene and aneurysmal subarachnoid hemorrhage in an Italian population

OBJECT: The results of genome-wide scan studies have suggested the presence of a genetic risk factor for aneurysmal subarachnoid hemorrhage (SAH) on chromosome 19 (at 19p13). The apolipoprotein E (APOE) gene is located in this chromosomal region and encodes a protein that exerts several neuroprotective and neurotrophic functions in the brain. The purpose of this study was to evaluate whether a particular allele or genotype of the APOE gene would modify the occurrence or the clinical features of SAH. METHODS: Genomic DNA was extracted from 146 patients with aneurysmal SAH and 222 age- and sex-matched healthy controls and genotyped for the triallelic polymorphism of the APOE gene (epsilon2, epsilon3, and epsilon4). Allele and genotype frequencies were compared between patients and controls. The clinical characteristics of the disease were compared according to the different APOE genotypes. Allele and genotype frequencies of the APOE gene polymorphism were nearly identical in cases and controls. Patients carrying the APOE epsilon4 allele had a significantly higher Hunt and Hess grade on admission (p = 0.0014). There was no significant relationship between any of the other clinical characteristics and the APOE genotype. CONCLUSIONS: The authors' data do not support the hypothesis that genetic variations within the APOE gene are associated with aneurysmal SAH. However, the APOE gene influences the disease phenotype and may be regarded as a disease modifier gene.     

Preliminary Report on the Association of Apolipoprotein E Polymorphisms, with Postoperative Peak Serum Creatinine Concentrations in Cardiac Surgical Patients

Background: Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated with major increases in morbidity, mortality, and cost. Genetic polymorphisms have been implicated as a factor in the progression of chronic renal disease, but a genetic basis for the development of acute renal impairment has not been investigated. The authors therefore tested the hypothesis that apolipoprotein E alleles are associated with different postoperative changes in serum creatinine after cardiac surgery.

Methods: The authors performed a prospective observational study with use of data from 564 coronary bypass surgical patients who were enrolled in an ongoing investigation of apolipoprotein E genotypes and organ dysfunction at a university hospital between 1989-1999. Renal function was assessed among apolipoprotein E genotype groups by comparisons of preoperative (CrPre), peak in-hospital postoperative (CrMax) and perioperative change (DCr) in serum creatinine values.

Results: The [epsilon]4 allele grouping (E2 = 2/2,2/3,2/4; E3 = 3/3; E4 = 3/4,4/4) was associated with a smaller increase in postoperative serum creatinine (perioperative change: E4, +0.17; E3, +0.26; E4, +0.27 mg/dl) and a lower peak postoperative creatinine than the [epsilon]2 and [epsilon]3 in univariate and multivariate analysis (peak in-hospital postoperative serum creatinine multivariate P = 0.015 vs. [epsilon]3, P = 0.038 vs. [epsilon]2). There was no difference in baseline creatinine among allele groups.     

The role of apolipoprotein E in cognitive decline after cardiac operation

BACKGROUND: Recently, Tardiff and colleagues have suggested that the presence of the apolipoprotein E, epsilon4 allele was associated with increased likelihood of cognitive decline after coronary artery bypass grafting. The objective of the current study was to replicate this earlier work using an increased sample size. The increased sample also enabled an analysis by individual genotype in cognitive decline after coronary artery bypass grafting. METHODS: Apolipoprotein E genotyping was performed on 111 individuals undergoing coronary artery bypass grafting. Each participant underwent a battery of nine neuropsychological tests before operation and 4 to 7 weeks after operation. RESULTS: Cognitive decline, assessed by both continuous Z change scores and two categoric measures of cognitive deficit, was not significantly associated with either individual apolipoprotein E genotypes or categorization by the presence or absence of the epsilon4 allele. The examination of potential moderating factors did not alter this finding. CONCLUSIONS: This study suggests that the epsilon4 allele is not associated with cognitive decline in the weeks after coronary artery bypass grafting.     

Prevalence of apolipoprotein E genotypes in ischaemic cerebrovascular disease in end-stage renal disease patients

Background. Several studies have demonstrated that atherosclerotic complications are the major cause of morbidity and mortality in end-stage renal disease (ESRD) patients on dialysis. The allele &egr;4 of apolipoprotein E (ApoE) gene has been associated with an increased risk for ischaemic cerebrovascular disease (ICVD) in general populations in recent preliminary cross-sectional studies. Methods. The aim of our study was to prospectively investigate the risk of ischaemic cerebrovascular disease wit respect to the presence of Apo &egr;4 allele in 157 Chinese uraemic patients. Results. During the 2 year follow-up, the incidence of stroke was 6.4% and the cumulative occurrence of ischaemic cerebrovascular disease was 9.6%. Further analysis showed that the cumulative occurrence of ischaemic cerebrovascular disease was 5.6% in subjects with no ApoE &egr;4 allele and 36.8% in those with one or two ApoE &agr;4 alleles. Univariate analysis showed that the prevalence of ischaemic cerebrovascular disease was significantly higher in the subjects with ApoE &egr;4 allele. The mean ApoA1 plasma concentrations was significantly lower in those with ApoE &egr;4 allele. A stepwise regression analysis showed that the presence of stroke was significantly related to the ApoE &egr;4 genotype (P<0.001). Conclusions. The ApoE &egr;4 allele can be regarded as an important risk factor for ischaemic cerebrovascular disease in uraemic patients.      

The influence of apolipoprotein E genotype on outcome after spontaneous subarachnoid hemorrhage: a preliminary study

OBJECTIVE: Possession of an apolipoprotein E (APOE)epsilon4 allele has been shown to be associated with a poor outcome after closed head injury and spontaneous intracerebral hemorrhage but not after ischemic stroke. This study assessed the influence of the APOE genotype on outcome in patients admitted to a neurosurgical unit with spontaneous subarachnoid hemorrhage. METHODS: A total of 100 patients with spontaneous subarachnoid hemorrhage were studied. Four patients were excluded because the diagnosis of subarachnoid hemorrhage was not confirmed. The incidence of rehemorrhage and delayed ischemia and the outcome at 6 months were determined using the Glasgow Outcome Scale. APOE genotypes were determined by polymerase chain reaction and restriction enzyme digestion. RESULTS: Allele frequencies in this patient group were 0.04 for epsilon2, 0.86 for epsilon3, and 0.1 for epsilon4. Of 96 patients, 72 had an aneurysmal hemorrhage and 1 had a hemorrhage from an arteriovenous malformation. In 14 patients, the results of angiography were negative, and in 9, no angiogram was performed. Of the 96 patients, 20 had one or more epsilon4 allele. Outcome at 6 months was no worse in patients with one or more epsilon4 allele than in those with no epsilon4 allele (odds ratio, 0.98; 95% confidence interval, 0.35-2.74). None of the 12 patients who experienced delayed ischemic deterioration had an epsilon4 allele. Of the 20 patients with an epsilon4 allele, 3 had a rehemorrhage, as compared with 6 of 76 patients without an epsilon4 allele. CONCLUSION: There was underrepresentation of the epsilon4 allele in this group when compared with previously studied cases of subarachnoid hemorrhage with a fatal outcome and with the general population. This suggests that patients with the epsilon4 allele who have a subarachnoid hemorrhage are less likely to be admitted to a neurosurgical unit. This study does not support an association between possession of an epsilon4 allele and poor outcome in patients admitted to a neurosurgical unit with spontaneous subarachnoid hemorrhage, although the wide confidence interval does not preclude a clinically relevant association between APOE genotype and outcome. The findings indicate that an association between genotype and the development of delayed ischemic complications after subarachnoid hemorrhage may be possible.     

Association between apolipoprotein E polymorphism and macroalbuminuria in patients with non-insulin dependent diabetes mellitus.

OBJECTIVES: Apolipoprotein E (apo E) is known to play an important role in lipoprotein metabolism through its ability to bind to the receptors as a ligand. Three different apo E alleles (epsilon2, epsilon3 and epsilon4) produce six apo E genotypes (epsilon2/2, epsilon2/3, epsilon2/4, epsilon3/3, epsilon3/4 and epsilon4/4). The objective of this study was to investigate an association between apo E gene polymorphism and macroalbuminuria in 167 Korean patients with non-insulin dependent diabetes mellitus (NIDDM). METHODS: The patients in the macroalbuminuria group (n = 74) represent those in whom 24 h urinary albumin excretion was above 300 mg. The patients in the normoalbuminuria group (n = 93) represent those in whom 24 h urinary albumin excretion was below 30 mg and serum creatinine levels were less than 1.2 mg/dl. The duration of diabetes in all patients was at least 8 years. RESULTS: There were no significant differences in terms of age, sex, body mass index, HbA1c, total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol between the two groups. In the macroalbuminuria group, the distribution of apo E genotypes revealed epsilon2/2 2 (2.7%), epsilon2/3 14 (18.9%), epsilon2/4 0 (0%), epsilon3/3 47 (63.5%), epsilon3/4 11 (14.9%) and epsilon4/4 0 (0%). In the normoalbuminuria group, the distribution of apo E genotypes revealed epsilon2/2 0 (0%), epsilon2/3 7 (7.5%), epsilon2/4 1 (1.1%), epsilon3/3 72 (77.4%), epsilon3/4 12 (12.9%) and epsilon4/4 1 (1.1%). There was no significant difference in the distribution of apo E genotypes between the two groups. However, there was a significant difference in the allele frequencies, epsilon2 frequency was significantly higher in macroalbuminuria group compared to normoalbuminuria group (12.2% vs 4.3%, P<0.05). Also, we compared apo E carrier frequencies between the two groups. Epsilon2 carrier frequency was significantly higher in macroalbuminuria group compared to normoalbuminuria group (21.6% vs 7.6%, P<0.05). In each group, there was no significant difference in the degree of lipid abnormalities between apo epsilon2 carrier (epsilon2/2, epsilon2/3 genotypes), epsilon3 carrier (epsilon3/3 genotype) and epsilon4 carrier (epsilon3/4, epsilon4/4 genotype). CONCLUSION: Apo epsilon2 allele and epsilon2 carrier frequencies were significantly higher in macroalbuminuria group. These results suggest that epsilon2 allele may be associated with the development of clinical albuminuria in Korean patients with NIDDM.     

Apolipoprotein E polymorphism and clinical course in childhood nephrotic syndrome

Numerous studies have reported on the role of apolipoprotein E (apoE) polymorphism in the progression of diseases associated with lipid abnormalities. However, few studies have been performed to date on the relationship between apoE polymorphism and childhood nephrotic syndrome (NS). In the present study, we evaluated the allelic and genotypic frequencies of the apoE gene and the possible association between the polymorphic forms of the apoE gene on the clinical course in 190 patients with childhood NS, who were further classified into frequent relapsers (FR, 92) and nonrelapsers or infrequent relapsers (IR, 98). Controls included 132 healthy Koreans. Allele-specific primers were used to detect polymorphism of the apoE gene. The allelic frequencies at the apoE locus were 5.9%, 82.6%, and 11.8% for alleles epsilon2, epsilon3, and epsilon4, respectively in the childhood NS group, while those in the control group were 6.8% for epsilon2, 88.3% for epsilon3, and 4.9% for epsilon4. The allelic frequency for epsilon4 in childhood NS was twice that of controls. Moreover, the allelic frequency of the epsilon4 allele in the FR group was 3.4 times that of the control group and 2.5 times that of the IR group. The high frequency of epsilon4 in patients with childhood NS suggests that epsilon4 may serve as a genetic marker for predisposition to childhood NS. We believe that the apoE allele type is of considerable significance in predicting the course of the disease.     

Frequency and effects of apolipoprotein E polymorphism in Mexican-American NIDDM subjects

We typed 254 non-insulin-dependent diabetic (NIDDM) Mexican Americans living in Starr County, Texas, for the three common apolipoprotein E (apoE) alleles. Typing was performed via DNA amplification and Hha I restriction. The allele frequencies (epsilon 2 = 0.041, epsilon 3 = 0.860, epsilon 4 = 0.099) were in Hardy-Weinberg equilibrium (chi 2 = 0.60, df = 3) and did not differ from a random sample from the same population (chi 2 = 0.16, df = 2). Analysis of variance was used to test for mean differences in lipid, lipoprotein, and glucose levels among apoE types. Significant differences among types were detected for low-density lipoprotein cholesterol (LDL-chol; P = 0.042, R2 = 2.6) and beta-lipoprotein cholesterol (P = 0.019, R2 = 3.3) levels. Mean LDL-chol in E2/3 individuals was 2.69 mM, E3/3 was 3.26 mM, and E4/3 was 3.36 mM. Mean beta-lipoprotein cholesterol in E2/3 individuals was 3.05 mM, E3/3 was 3.64 mM, and E4/3 was 3.67 mM. Based on these results, we conclude that the effects of the apoE polymorphism on lipid profiles and glucose levels are the same in NIDDM subjects as in nondiabetic Mexican Americans and other populations. Other studies investigating the role of apoE polymorphism in diabetic subjects have found increased triglyceride levels in individuals possessing an epsilon 2-allele and an increased frequency of the epsilon 2-allele in hyperlipidemic diabetic subjects. We found no significant difference in mean triglyceride levels among genotypes. Possible reasons for this discrepancy are discussed, including DNA- versus protein-typing methods.