ABSTRACT
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.
Subject(s)
Apolipoprotein A-I/genetics , Apolipoproteins A/genetics , Cardiovascular Diseases/genetics , Cholesterol, LDL/genetics , Cholesterol/genetics , Aged , Aged, 80 and over , Apolipoprotein A-V , Brazil , Cholesterol/blood , Cholesterol, LDL/blood , Female , Gene Frequency , Genetic Association Studies , Haplotypes , Humans , Linkage Disequilibrium , Male , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic function as well as impaired immune response. Using high-resolution microarrays we evaluated the gene expression profiles of healthy male volunteers who underwent 60 h of prolonged wakefulness (PW) followed by 12 h of sleep recovery (SR). Peripheral whole blood was collected at 8 am in the morning before the initiation of PW (Baseline), after the second night of PW, and one night after SR. We identified over 500 genes that were differentially expressed. Notably, these genes were related to DNA damage and repair and stress response, as well as diverse immune system responses, such as natural killer pathways including killer cell lectin-like receptors family, as well as granzymes and T-cell receptors, which play important roles in host defense. These results support the idea that sleep loss can lead to alterations in molecular processes that result in perturbation of cellular immunity, induction of inflammatory responses, and homeostatic imbalance. Moreover, expression of multiple genes was downregulated following PW and upregulated after SR compared with PW, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC, and CEACAM genes confirmed previous findings related to the molecular effects of sleep deprivation. Thus, the present findings confirm that the effects of sleep loss are not restricted to the brain and can occur intensely in peripheral tissues.
Subject(s)
Genome, Human , Sleep/genetics , Transcriptome , Wakefulness/genetics , Adult , Calcium-Binding Proteins/blood , Calcium-Binding Proteins/genetics , Cell Adhesion Molecules/blood , Cell Adhesion Molecules/genetics , Circadian Rhythm , Gene Expression Profiling , Globins/metabolism , Humans , Male , Sleep/physiology , Sleep Deprivation/genetics , Wakefulness/physiologyABSTRACT
BACKGROUND: The purpose of this study was to evaluate the influence of polymorphism on sleep parameters of Obstructive Sleep Apnea Syndrome (OSAS) patients. METHODS: Patients were genotyped after a full-night polysomnography using the large Epidemiologic Sleep Study of São Paulo population-based sample. RESULTS: Individuals who carry the APOE ε2 allele showed longer sleep latency, lower sleep efficiency and higher numbers of arousals/hour, when compared to ε3 allele homozygous and carriers of ε4 allele (p<0.05). These findings remained significant even after correction for potential confounders, such as sex, age and African genetic ancestry. CONCLUSION: The APOE polymorphisms may modulate the effects of intermittent hypoxia and sleep fragmentation in the sleep architecture of OSAS patients, and that the presence of the ε2 allele may serve as a biological marker for the identification of a subgroup of patients who are more likely to suffer with OSAS detrimental effects on sleep, impacting not only the daily functioning, but also their quality of life.