Search tips
Search criteria

Results 1-6 (6)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer’s disease 
Acetylcholinesterase inhibitors (AChEIs) may reduce the oxidative stress in brain of Alzheimer’s disease (AD) patients. Forkhead box O1 (FOXO1) protein has been reported as the link between oxidative stress and AD. We evaluated a potential association between FOXO1 gene locus and the response to AChEI treatment in patients with sporadic AD.
In this prospective study, 109 Caucasian AD patients were treated with standard doses of donepezil, galantamine, or rivastigmine for 6 months. Functional and cognitive status were evaluated at baseline and after treatment. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Genotype analyses, including the APOE polymorphism, were made in blinded fashion.
A significantly higher frequency of FOXO1 rs7981045 G/G genotype was observed in nonresponders compared with responders (17.14% versus 2.70%, P=0.010). Age, sex, and APOE-adjusted logistic regression analysis confirmed that patients with the G/G genotype had a significantly higher risk of poor response to AChEI treatment (odds ratio =10.310; 95% confidence interval, 1.510–70.362). Haplotype analysis revealed significant differences in haplotype frequency distribution between these groups.
FOXO1 may influence the clinical response to AChEIs in AD patients.
PMCID: PMC4211854  PMID: 25364236
forkhead box O1; acetylcholinesterase inhibitors; response to treatment
2.  Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease 
Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO) concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD), a common medical condition in the elderly. Flow-mediated dilation (FMD), a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1) and after (phase 2) standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001), pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001), pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001), FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001) and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001). FMD values were positively correlated with pCO2 values (r=0.294, P=0.004) at baseline. A significant correlation was also found between relative changes in FMD and pCO2 levels, passing from phase 1 to phase 2 (r=0.23, P=0.023). Patients with higher baseline endothelium-dependent vasodilation as evaluated by FMD showed greater modification with regard to pCO2 changes (2.6±1.39 versus 1.59±1.4, P=0.012). In conclusion, endothelium-dependent vasodilation as evaluated by FMD was elevated during hypercapnia, and varied significantly according to pCO2 changes in patients with higher baseline levels, suggesting that vascular reactivity in acute COPD exacerbations in the elderly depends on integrity of the vascular endothelium.
PMCID: PMC4043425  PMID: 24904207
hypercapnia; elderly; chronic obstructive pulmonary disease; vascular reactivity; flow-mediated dilation
3.  Klotho locus, metabolic traits, and serum hemoglobin in hospitalized older patients: a genetic association analysis 
Age  2011;34(4):949-968.
Klotho (KL) gene has been involved in severe alterations of physiological biochemical parameters leading to premature aging-like phenotypes and strikingly shortening lifespan. KL participates to the regulation of a number of intracellular biochemical pathways, including lipid profile and glucose metabolism. Aim of this study was to investigate the possible association between KL locus and biological parameters commonly accepted as indicators of the clinical status in hospitalized older patients. We genotyped the single-nucleotide polymorphisms (SNPs) rs9536314, rs1207568, and rs564481 at the KL locus in 594 hospitalized older patients (65–99 years), consecutively attending a geriatric ward, and tested the association of these KL variants with biological quantitative traits using analyses of covariance and genetic risk score models. Significant associations of rs9536314 with serum levels of hemoglobin, albumin, and high-density lipoprotein cholesterol (HDL-C) as well as significant associations of rs564481 with serum levels of hemoglobin, fasting insulin, and fasting glucose were observed. Gender-segregated analyses confirmed these associations, and suggested that the associations of KL genotypes with HDL-C, fasting glucose and fasting insulin levels may be driven by the female gender, while the association with serum levels of hemoglobin may be driven by the male gender. The association of KL genotypes with creatinine levels was found only in females, while the association with insulin-like growth factor-1 (IGF-1) and lymphocytes count (LC) was found only in males. The genetic risk score (GRS) models further confirmed significant associations among KL SNPs and hemoglobin, total cholesterol, and HDL-C. Gender-segregated analyses with the GRS-tagged approach confirmed the associations with HDL-C, fasting glucose, and fasting insulin levels in females, and with hemoglobin and LC in males. Our findings suggested that KL locus may influence quantitative traits such as serum levels of lipid, fasting glucose, albumin and hemoglobin in hospitalized older patients, with some gender differences suggested for creatinine, IGF-1 levels, and LC, thus being one of the genetic factors possibly contributing to age-related diseases and longevity.
PMCID: PMC3682056  PMID: 21695423
Klotho; Chromosome 13; High-density lipoprotein cholesterol; Total cholesterol; Fasting glucose; Fasting insulin; Insulin-like growth factor-1; Hemoglobin; Creatinine; Albumin; Lymphocytes
4.  Angiotensin-converting enzyme (ACE) genotypes and disability in hospitalized older patients 
Age  2010;33(3):409-419.
The association between angiotensin-converting enzyme (ACE) genotypes and functional decline in older adults remains controversial. To assess if ACE gene variations influences functional abilities at older age, the present study explored the association between the common ACE insertion/deletion (I/D) polymorphism and disability measured with activities of daily living (ADL) in hospitalized older patients. We analyzed the frequency of the ACE genotypes (I/I, I/D, and D/D) in a population of 2,128 hospitalized older patients divided according to presence or absence of ADL disability. Logistic regression analysis adjusted for possible confounding factors, identified an association between the I/I genotype with ADL disability (OR = 1.54, 95% CI 1.04–2.29). This association was significant in men (OR = 2.01, 95% CI 1.07–3.78), but not in women (OR = 1.36, 95% CI 0.82–2.25). These results suggested a possible role of the ACE polymorphism as a genetic marker for ADL disability in hospitalized older patients.
PMCID: PMC3168594  PMID: 21076879
Angiotensin-converting enzyme; Disability; Aging; Hospitalized patients
5.  Effect of Obesity, Serum Lipoproteins, and Apolipoprotein E Genotypes on Mortality in Hospitalized Elderly Patients 
Rejuvenation Research  2011;14(2):111-118.
The aim of this study was to investigate the relationship among apolipoprotein E (APOE) polymorphism, body mass index (BMI), and dyslipidemia and how these factors modify overall mortality in a cohort of hospitalized elderly patients.
Plasma concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), BMI, and APOE genotype were evaluated in 1,012 hospitalized elderly patients, who were stratified into three groups according to their baseline BMI and APOE allele status. Multivariate logistic regression analysis was used to assess whether APOE genotype, BMI, and dyslipidemia are associated with mortality, adjusting for potential confounders. Interaction analysis was also performed.
Obese patients have significantly higher levels of TC and LDL-C compared to normal-weight and overweight subjects, for both sexes. APOE ε4 carriers have significantly higher levels of TC and LDL-C compared with ε2 and ε3 carrier both in males and females. Interaction analysis showed that women with TC < 180 mg/dL, LDL-C < 100 mg/dL, normal weight, and ε3 carrier (odds ratio [OR] = 3.42, 95% confidence interval [CI] 1.36–8.60) and men with LDL-C < 100 mg/dL, HDL-C < 40 mg/dL, and ε3 carrier (OR = 1.97, 95% CI 1.04–3.74) were at highest risk of mortality.
In elderly hospitalized patients, obesity and APOE genotype influence the lipid profile and mortality risk. A significant interaction among BMI, dyslipidemia, and APOE genotype was observed that could identify elderly patients with different risks of mortality.
PMCID: PMC3092981  PMID: 21595502
6.  Circulating HMW adiponectin isoform is heritable and shares a common genetic background with insulin resistance in non diabetic White Caucasians from Italy: evidence from a family-based study 
Journal of internal medicine  2009;267(3):287-294.
Reduced circulating adiponectin levels contribute to the etiology of insulin-resistance. Adiponectin circulates in three different isoforms: high (HMW), medium (MMW), and low (LMW) molecular weight. The genetics of adiponectin isoforms is mostly unknown. Our aim was to investigate whether and to which extent circulating adiponectin isoforms are heritable and whether they share common genetic backgrounds with insulin resistance-related traits.
In a family based sample of 640 non diabetic White Caucasians from Italy, serum adiponectin isoforms concentrations were measured by ELISA. Three SNPs in the ADIPOQ gene previously reported to affect total adiponectin levels (rs17300539, rs1501299 and rs677395) were genotyped. The heritability of adiponectin isoform levels was assessed by variance component analysis. A linear mixed effects model was used to test association between SNPs and adiponectin isoforms. Bivariate analyses were conducted to study genetic correlations between adiponectin isoforms levels and other insulin resistance-related traits.
All isoforms were highly heritable (h2=0.60−0.80, p=1×10−13–1×10−23). SNPs rs17300539, rs1501299 and rs6773957 explained a significant proportion of HMW variance (2–9%, p=1×10−3–1×10−5). In a multiple-SNP model, only rs17300539 and rs1501299 remained associated with HMW adiponectin (p=3×10−4 and 2.0×10−2). Significant genetic correlations (p=1×10−2–1×10−5) were observed between HMW adiponectin and fasting insulin, HOMAIR, HDL-cholesterol and the metabolic syndrome score. Only rs1501299 partly accounted for these genetic correlations.
Circulating levels of adiponectin isoforms are highly heritable. The genetic control of HMW adiponectin is shared in part with insulin resistance-related traits and involves, but is not limited to the ADIPOQ locus.
PMCID: PMC2833228  PMID: 19761474
ADIPOQ gene; Adiponectin isoforms; insulin resistance

Results 1-6 (6)