Lara Miguel Quirino Araújo

Association of PPARα gene polymorphisms and lipid serum levels in a Brazilian elderly population

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear transcription factor strictly involved in lipid and lipoprotein metabolisms. Thus, PPARalpha gene polymorphisms have been investigated as cardiovascular risk factors. We aimed to investigate associations of L162V and intron 7G>C polymorphisms with common morbidities affecting a Brazilian elderly cohort as well as with lipid and protein serum levels. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP), and allele frequencies were determined. In addition, we performed the linkage disequilibrium analysis. Descriptive statistics, logistic regression analysis, and Students t-test were used. Rare alleles for L162V and intron 7 G>C polymorphisms showed frequencies of 0.047 and 0.199, respectively. Our data showed that these polymorphisms were in linkage disequilibrium (p=0.0002). Intron 7 G>C polymorphism presented a tendency of association with neoplasia (p=0.053), and C allele was associated with higher HDL (p=0.010), lower triglycerides (p=0.001), and VLDL levels (p=0.003) compared to G allele. These data might suggest a protective role of intron 7 G>C polymorphism in the development of cardiovascular diseases and will help to clarify the importance of PPARalpha polymorphisms as key modulators of lipid metabolism in Brazilian population.

Frequency of Werner helicase 1367 polymorphism and age-related morbidity in an elderly Brazilian population

Werner syndrome (WS) is a premature aging disease caused by a mutation in the WRN gene. The gene was identified in 1996 and its product acts as a DNA helicase and exonuclease. Some specific WRN polymorphic variants were associated with increased risk for cardiovascular diseases. The identification of genetic polymorphisms as risk factors for complex diseases affecting older people can improve their prevention, diagnosis and prognosis. We investigated WRN codon 1367 polymorphism in 383 residents in a district of the city of São Paulo, who were enrolled in an Elderly Brazilian Longitudinal Study. Their mean age was 79.70 +/- 5.32 years, ranging from 67 to 97. This population was composed of 262 females (68.4%) and 121 males (31.6%) of European (89.2%), Japanese (3.3%), Middle Eastern (1.81%), and mixed and/or other origins (5.7%). There are no studies concerning this polymorphism in Brazilian population. These subjects were evaluated clinically every two years. The major health problems and morbidities affecting this cohort were cardiovascular diseases (21.7%), hypertension (83.7%), diabetes (63.3%), obesity (41.23%), dementia (8.0%), depression (20.0%), and neoplasia (10.8%). Their prevalence is similar to some urban elderly Brazilian samples. DNA was isolated from blood cells, amplified by PCR and digested with PmaCI. Allele frequencies were 0.788 for the cysteine and 0.211 for the arginine. Genotype distributions were within that expected for the Hardy-Weinberg equilibrium. Female gender was associated with hypertension and obesity. Logistic regression analysis did not detect significant association between the polymorphism and morbidity. These findings confirm those from Europeans and differ from Japanese population.

Association of lipase lipoprotein polymorphisms with myocardial infarction and lipid levels

Abstract Background: Lipoprotein lipase has an important role in lipid metabolism. Elevated levels of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) are associated with increased risk of coronary artery disease and low levels of high-density lipoprotein (HDL) are potentially atherogenic. The HindIII and S447X polymorphisms of the lipoprotein lipase (LPL) gene are associated with cardiovascular disease in some populations. Methods: LPL HindIII and S447X polymorphisms were analyzed in 343 individuals of 66–97 years of age from a cohort of a Brazilian elderly longitudinal study. Allele frequencies, genotype distribution and allele association with major morbidities and with serum lipid, urea, creatinine and albumin levels were also investigated. The whole sample was genotyped by PCR-restriction fragment length polymorphism (RFLP). Descriptive statistics, logistic regression analysis and t-test were used. Results: Allele frequencies were H+=0.652 and H–=0.348 for LPL HindIII and S=0.824 and X=0.176 for LPL S447X polymorphism. Both polymorphisms have frequencies similar to those in some European populations. LPL HindIII polymorphism showed significant association of the H+ allele with myocardial infarction. The H– allele showed a tendency to associate with higher HDL levels. The LPL S447X S allele was associated with higher triglyceride levels. Conclusions: These findings may help to identify risk factors for subjects and families and clarify the physiopathological role of these polymorphisms in age-related diseases. Clin Chem Lab Med 2007;45:599–604.

Association of the apolipoprotein A-IV: 360 Gln/His polymorphism with cerebrovascular disease, obesity, and depression in a Brazilian elderly population.

The identification of genetic polymorphisms as risk factors for complex diseases can be relevant for their prevention, diagnosis, and prognosis. The apolipoprotein A‐IV: 360 Gln/His polymorphism was investigated in 383 elderly individuals, who were participants of a longitudinal study commenced in 1991. The major morbidities that affect elderly people, such as cardiovascular diseases, diabetes, low cognitive function, depression, and obesity, were extensively investigated. DNA was isolated from blood cells, amplified by PCR, and digested with Fnu4HI. In this population the frequency of the His allele was 0.056 and the genotypes were distributed according to Hardy–Weinberg equilibrium. Logistic regression analysis showed a significant association between the presence of His allele and cerebrovascular disease and/or transitory ischemic attack (odds ratio) (OR = 3.070, P = 0.027), obesity (OR = 2.241, P = 0.047), and depression (OR = 2.879, P = 0.005). This study indicates that the presence of the rare allele in elderly people can play a significant role in the occurrence of multifactorial diseases. This is the first study analyzing this polymorphism in elderly people in Brazil. More studies should be encouraged to elucidate the mechanisms involved in these diseases.

Association of APOA1 and APOA5 polymorphisms and haplotypes with lipid parameters in a Brazilian elderly cohort.

Apolipoproteins have an important role in lipid metabolism and transport. Polymorphisms in the APOA1/C3/A4/A5 gene cluster have been associated with lipid alterations and cardiovascular diseases. We investigated APOA1 XmnI, APOA5 S19W, and APOA5 -1131T>C polymorphisms in 377 individuals from a cohort of a longitudinal Brazilian elderly study. Allele frequencies, genotype distribution, and association with major morbidities as well as with lipids, creatinine, albumin, urea, glycated hemoglobin, and fasting glucose serum levels were investigated. Linkage disequilibrium and haplotype associations were also analyzed. This is the first time that haplotypes involving these polymorphisms were evaluated. Genotyping was performed by PCR-RFLP. Minor allele frequencies were 0.119, 0.071, and 0.158 for XmnI, S19W, and -1131T>C polymorphisms, respectively. We found a significant association of the -1131C allele with low LDL-C levels. We also observed that XmnI and S19W polymorphisms were in linkage disequilibrium. The C/G haplotype, which is composed of the wild-type allele of XmnI and the minor allele of S19W, was associated with high total cholesterol serum levels in this elderly population. We conclude that the -1131T>C polymorphism and the C/G haplotype, including XmnI and S19W polymorphisms, are associated with alterations in lipid levels and may be risk factors for cardiovascular disease in the Brazilian elderly.

APOA4 polymorphism as a risk factor for unfavorable lipid serum profile and depression: a cross-sectional study.

Introduction APOA1/C3/A4/A5 gene cluster is closely involved in lipid metabolism, and its polymorphisms have been associated with coronary heart disease and lipid plasma levels. Here, we aimed to investigate associations of APOC3 (3238C>G, −482C>T, 1100C>T) and APOA4 (Gln360His, Thr347Ser) polymorphisms in 382 individuals from a cohort of a Longitudinal Brazilian Elderly Study with major age-related morbidities and with lipid and protein serum levels. Materials and Methods The whole sample was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Descriptive statistics, logistic regression analysis, Student t test, deviation from Hardy-Weinberg, Bonferroni correction for multiple testing, and haplotype analyses were performed. Results Although APOC3 1100T allele carriers presented lower triglyceride and very low density lipoprotein levels than non-T carriers, these associations disappeared after Bonferroni correction (P > 0.05). Moreover, APOA4 360His allele was associated with depression (P = 0.03), increased triglyceride (P = 0.035) and very low density lipoprotein (P = 0.035) levels, and reduced HDL levels (P = 0.0005). Haplotype analyses found an association between His/C/C haplotype (Gln360His/−482C>T/1100C>T) with depression, but this result was due to Gln360His polymorphism. Conclusions Our data suggest that 360His allele might be a risk factor for depression and unfavorable lipid profile and depression for elderly people in the Brazilian population.

APO A-V-1131T-->C polymorphism frequency and its association with morbidity in a Brazilian elderly population.

Abstract Identification of genetic polymorphisms as risk factors for complex diseases affecting older people can be relevant for their prevention, diagnosis and management. The –1131T→C polymorphism of the apolipoprotein A-V gene (APO A-V) is tightly linked to lipid metabolism and has been associated with increased triglyceride levels and familial dyslipidemia. The aims of this study were to analyze the allele and genotype frequencies of this polymorphism in a Brazilian elderly population and to investigate any association between the polymorphism and major morbidities affecting elderly people. This polymorphism was investigated in 371 individuals, aged 66–97years, in a Brazilian Elderly Longitudinal Population Study. Major morbidities investigated were: cerebrovascular diseases (CVD); myocardial infarction (MI); type 2 diabetes; hypertension; obesity; dementia; depression; and neoplasia. DNA was isolated and amplified by PCR and its products were digested with restriction enzyme Tru1I. T and C allele frequencies were 0.842 and 0.158, respectively. Our population showed allele frequencies that were similar to European and Afro-American and different from Asiatic populations. Genotype distributions were not within Hardy-Weinberg equilibrium only for the obesity subject sample. On the other hand, a significant association between the C allele and obesity in the presence of CVD×depression interaction was observed. Logistic analysis showed no association of the polymorphism with each morbidity group. Therefore, the C allele in elderly Brazilian subjects may represent a risk factor for these morbidity interactions, which may lead to better comprehension of their pathophysiology.

Approaches that use software to support the prevention of pressure ulcer: A systematic review.

CONTEXT The incidence and costs for pressure ulcer (PU) treatment remain high even though preventive methods are applied. Approaches that use software to support the prevention of PU are presented in the literature to make it more effective. OBJECTIVES Identify the state of art of the approaches that use software to support the prevention of PUs. METHODS A systematic literature review was performed to analyze approaches that use software to support the prevention of PU. ACM, IEEE, PubMed, Scopus, CINAHL and Embase databases have been searched with a predetermined search string to identify primary studies. We selected the ones that met the established inclusion criteria. RESULTS Thirty-six articles met the inclusion criteria. To support prevention, most approaches monitor the patient to provide information about exposure to pressure, temperature level, humidity level and estimated body position in bed providing risk factor intensity charts and intensity maps. The main method to perform patients monitoring is using sensors installed on the mattress, but recently, alternative methods have been proposed such as electronic sensors and tactile sensory coils. Part of the approaches performs automated management of the risk factors using ventilation tubes and mattresses with porous cells to decrease bodys temperature and movable cells to automatically redistribute the pressure over the body. Matters as cost of the approach, patient comfort and hygiene of the monitoring equipment is only briefly discussed in the selected articles. No experiments have been conducted to evidence the approached may reduce PU incidence. DISCUSSION AND CONCLUSION Currently, approaches that use software to support the prevention of PU provide relevant information to health professionals such as risk factor intensity charts and intensity maps. Some of them can even automatically manage risk factors in a limited way. Yet, the approaches are based on risk factor monitoring methods that require patients contact with the monitoring equipment. Therefore, some matters need to be considered such as patients comfort and the hygiene or replacement of the equipment due to the risk of infection. With the emergence of new alternative methods of monitoring, new technologies that do not require contact could be explored by new researches. Randomized Control Trials could also be conducted to verify which approaches are really effective to reduce PU incidence.

A importância do HDL-C e da PCR na avaliação do risco cardiovascular em idosos longevos

The association between total mortality, lipoproteinS, and inflammatory markers, and their implications with aging and longevity are often controversial. Among the most often studied markers are low HDL cholesterol and high C-reactive protein. Particularly in octogenarians, it is expected that the impact of the inclusion of HDL cholesterol and C-reactive protein will improve the stratification of absolute cardiovascular risk. In the present study, we performed a literature review in PubMed about the relation between HDL cholesterol, inflammation and longevity. Applying the inclusion and exclusion criteria adopted, we selected 30 studies, among which one systematic review on the relation between HDL cholesterol and stroke, one meta-analysis on the relation between total cholesterol and HDL cholesterol with mortality, 22 longitudinal studies, and six cross-sectional studies. The results show an inverse association between HDL cholesterol and total mortality, and between cardiovascular mortality and C-reactive protein, as well as a positive association between C-reactive protein and mortality in longevous individuals. C-reactive protein and HDL cholesterol displayed promising characteristics as predictors of cardiovascular mortality in longevous elderly persons.

Association between increased serum thyrotropin concentration and the oldest old: what do we know?

To assess studies that evaluate the relation between serum thyrotropin concentration, very old subjects, and their events. We searched the PubMed, SciELO, and LILACS databases for articles published between 2004 and 2012. Our search was restricted to studies involving humans aged 65 years or older, and written in English, Spanish, or Portuguese. Studies that evaluated the association between elevated serum thyrotropin concentration among elderly subjects with subclinical hypothyroidism were chosen since at least in part they included a subpopulation of individuals aged 80 years and above. Thirteen studies were selected. No significant increase in risk of cardiovascular events, coronary heart disease, or total mortality was observed. Elevated thyrotropin concentration was associated with longevity. More randomized controlled trials are required to better define the potential benefits of elevated thyrotropin concentration in this oldest old population, hormone replacement, and longevity.