Background and purpose: Low levels of insulin-like growth factor I (IGF- I) predispose to atherosclerosis and may therefore increase the risk of stroke. Low levels have also been found to influence the outcome of card...Background and purpose: Low levels of insulin-like growth factor I (IGF- I) predispose to atherosclerosis and may therefore increase the risk of stroke. Low levels have also been found to influence the outcome of cardiovascular and cerebrovascular disease. A polymorphism in the promoter region of the IGF-I gene influences IGF-I levels. Non-carriers of the 192 bp allele have lower levels of IGF-I compared with 192 bp allele carriers. We studied the IGF-I polymorphism in relation to the risk of stroke and survival after stroke. Methods: We studied 6808 subjects of the Rotterdam Study, who were followed for the occurrence of stroke and death after stroke. Subjects were grouped according to the 192 bp allele of IGF-I into non-carriers, heterozygotes, and homozygotes. The risk of stroke and survival after stroke was studied using Cox regression analysis, adjusting for age and sex, with homozygotes for the wildtype allele as the reference. Results: Non-carriers had a relative risk of 0.8 (95% Cl: 0.6 to 1.0) for the occurrence of any stroke and 0.7 (95% Cl: 0.5 to 1.0) for ischaemic stroke. For non-carriers, the relative risk of death after any stroke was 1.5 (95% Cl: 1.0 to 2.2). After an ischaemic stroke, this relative risk was 1.5 (95% Cl: 0.9 to 2.6) and after a haemorrhagic stroke 5.2 (95% Cl: 1.3 to 21.5). Conclusions: Our study suggests that IGF-I is a significant determinant of survival after stroke.展开更多
Background and Purpose -Using 930 individuals connected in a single pedigree from an isolated population, participants of the Erasmus Rucphen Family (ERF) study, we investigated the heritability of carotid-femoral pul...Background and Purpose -Using 930 individuals connected in a single pedigree from an isolated population, participants of the Erasmus Rucphen Family (ERF) study, we investigated the heritability of carotid-femoral pulse wave velocity (PWV), carotid intima media thickness (IMT), and carotid plaque score. Methods -PWV was measured between the carotid and femoral arteries as an indicator of aortic stiffness. Common carotid IMT and plaque score, quantifying alterations in arterial wall structure, were measured by ultrasonography. Results -All 3 traits were significantly associated with classic cardiovascular risk factors. Age-and gender-adjusted heritability estimates were 0.36 for PWV, 0.41 for carotid IMT, and 0.28 for plaque score. After adjustment for appropriate risk factors, the heritabilities were 0.26, 0.35, and 0.21 for PWV, IMT, and plaque score, respectively. All heritability estimates were statistically significant (P < 0.001). Taking into account different proportions of variance associated with covariates for each trait, genetic factors explained ≈12%of the total variability for each of the pheno types. Conclusions -To our knowledge, this is the first report on the heritabi lity of PWV. The heritability estimates of IMT and plaque score were similar to those in previous reports. We conclude that genetic factors significantly contri bute to arterial structure and function in this isolated population, presenting the opportunity to locate susceptibility genes related to cardiovascular disorde rs.展开更多
Objectives: The most common familial early onset dementia mutations are found in the genes involved in Alzheimer’ s disease; the amyloid precursor protein (APP) and the presenilin 1 and 2 (PSEN1 and 2) genes; the pri...Objectives: The most common familial early onset dementia mutations are found in the genes involved in Alzheimer’ s disease; the amyloid precursor protein (APP) and the presenilin 1 and 2 (PSEN1 and 2) genes; the prion protein gene (PRNP) may be involved. Methods: Following identification of a two octapeptide repeat insertion in PRNP, we conducted a meta analysis to investigate the relation of number of PRNP octapeptide repeats with age at disease onset and duration of illness; identifying 55 patients with PRNP octapeptide repeat insertions. We used a linear mixed effects model to assess the relation of number of repeats with age at disease onset, and studied the effect of the number of inserted octapeptide repeats on disease duration with a Cox proportional hazards regression analysis. Results: We found an increasing number of repeats associated with younger age at onset (p < 0.001). Duration of the disease decreased significantly with the length of the octapeptide repeat (p < 0,001) when adjusting for age at onset. Conclusions: Our findings showsignificant inverse associations of the length of the PRNP octapeptide repeat with age at disease onset and disease duration in the spongiform encephalopathies.展开更多
文摘Background and purpose: Low levels of insulin-like growth factor I (IGF- I) predispose to atherosclerosis and may therefore increase the risk of stroke. Low levels have also been found to influence the outcome of cardiovascular and cerebrovascular disease. A polymorphism in the promoter region of the IGF-I gene influences IGF-I levels. Non-carriers of the 192 bp allele have lower levels of IGF-I compared with 192 bp allele carriers. We studied the IGF-I polymorphism in relation to the risk of stroke and survival after stroke. Methods: We studied 6808 subjects of the Rotterdam Study, who were followed for the occurrence of stroke and death after stroke. Subjects were grouped according to the 192 bp allele of IGF-I into non-carriers, heterozygotes, and homozygotes. The risk of stroke and survival after stroke was studied using Cox regression analysis, adjusting for age and sex, with homozygotes for the wildtype allele as the reference. Results: Non-carriers had a relative risk of 0.8 (95% Cl: 0.6 to 1.0) for the occurrence of any stroke and 0.7 (95% Cl: 0.5 to 1.0) for ischaemic stroke. For non-carriers, the relative risk of death after any stroke was 1.5 (95% Cl: 1.0 to 2.2). After an ischaemic stroke, this relative risk was 1.5 (95% Cl: 0.9 to 2.6) and after a haemorrhagic stroke 5.2 (95% Cl: 1.3 to 21.5). Conclusions: Our study suggests that IGF-I is a significant determinant of survival after stroke.
文摘Background and Purpose -Using 930 individuals connected in a single pedigree from an isolated population, participants of the Erasmus Rucphen Family (ERF) study, we investigated the heritability of carotid-femoral pulse wave velocity (PWV), carotid intima media thickness (IMT), and carotid plaque score. Methods -PWV was measured between the carotid and femoral arteries as an indicator of aortic stiffness. Common carotid IMT and plaque score, quantifying alterations in arterial wall structure, were measured by ultrasonography. Results -All 3 traits were significantly associated with classic cardiovascular risk factors. Age-and gender-adjusted heritability estimates were 0.36 for PWV, 0.41 for carotid IMT, and 0.28 for plaque score. After adjustment for appropriate risk factors, the heritabilities were 0.26, 0.35, and 0.21 for PWV, IMT, and plaque score, respectively. All heritability estimates were statistically significant (P < 0.001). Taking into account different proportions of variance associated with covariates for each trait, genetic factors explained ≈12%of the total variability for each of the pheno types. Conclusions -To our knowledge, this is the first report on the heritabi lity of PWV. The heritability estimates of IMT and plaque score were similar to those in previous reports. We conclude that genetic factors significantly contri bute to arterial structure and function in this isolated population, presenting the opportunity to locate susceptibility genes related to cardiovascular disorde rs.
文摘Objectives: The most common familial early onset dementia mutations are found in the genes involved in Alzheimer’ s disease; the amyloid precursor protein (APP) and the presenilin 1 and 2 (PSEN1 and 2) genes; the prion protein gene (PRNP) may be involved. Methods: Following identification of a two octapeptide repeat insertion in PRNP, we conducted a meta analysis to investigate the relation of number of PRNP octapeptide repeats with age at disease onset and duration of illness; identifying 55 patients with PRNP octapeptide repeat insertions. We used a linear mixed effects model to assess the relation of number of repeats with age at disease onset, and studied the effect of the number of inserted octapeptide repeats on disease duration with a Cox proportional hazards regression analysis. Results: We found an increasing number of repeats associated with younger age at onset (p < 0.001). Duration of the disease decreased significantly with the length of the octapeptide repeat (p < 0,001) when adjusting for age at onset. Conclusions: Our findings showsignificant inverse associations of the length of the PRNP octapeptide repeat with age at disease onset and disease duration in the spongiform encephalopathies.
