ABSTRACT
OBJECTIVE: Serotonin (5-HT) is a pleiotropic molecule that exerts several functions on brain and peripheral tissues via different receptors. The gene for the 5-HT2A receptor shows some variations, including a T102C polymorphism, that have been associated with increased risk of neuropsychiatric and vascular disorders. However, the potential impact of 5-HT2A imbalance caused by genetic variations on the human lifespan has not yet been established. METHODS: We performed a prospective study involving an Amazon riparian elderly free-living population in Maués City, Brazil, with a 5-year follow-up. Out of a cohort of 637 subjects selected in July, 2009, we genotyped 471 individuals, including 209 males (44.4%) and 262 females (55.6%), all averaging 72.3 ± 7.8 years of age (ranging from 60 to 100 years). RESULTS: The T102C-SNP genotypic frequencies were 14.0% TT, 28.0% CC, and 58.0% CT. From 80 elderly individuals who died during the period investigated, we observed significantly (P = .005) higher numbers of TT carriers (27.3%) and CC carriers (21.2%), compared to heterozygous CT carriers (12.5%). Cox-regression analysis showed that association between the T102C-SNP and elderly survival was independent of age, sex, and other health variables. CONCLUSIONS: Our findings strongly suggest that imbalance in 5-HT2A may cause significant disturbances that lead to an increased susceptibility to death for individuals who are over 60 years of age.
Subject(s)
Mortality , Polymorphism, Genetic , Receptor, Serotonin, 5-HT2A/genetics , Aged , Aged, 80 and over , Brazil , Cities , Female , Humans , Male , Middle Aged , Prospective Studies , Receptor, Serotonin, 5-HT2A/metabolism , RiskABSTRACT
ABSTRACT INTRODUCTION: Obesity is related to the possibility of a number of metabolic damage associated with oxidative stress. The enzymes of the glutathione S-transferase (GST) family have the function of promoting detoxification; however, polymorphisms in the glutathione S-transferase P1 (GSTP1) gene generate less efficient alleles as well as a decrease in their amount and activity. OBJECTIVE: This study aimed to analyze the frequency of the alleles (A and G) and the genotypes of the GSTP1 Ile105Val gene polymorphism, and its association with obesity in the elderly. MATERIALS AND METHODS: This was a cross-sectional study involving 232 subjects aged between 60-98 years, of both sexes, originating from southern Brazil. The volunteers were categorized according to the body mass index (BMI) in three groups: normal weight (n = 52), overweight (n = 133), and obese (n = 47). Anthropometry was evaluated and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genetic analysis, from peripheral blood samples. RESULTS: The allelic frequency in the elderly obese group was 37.2% for A and 62.8% for G allele, and the genotypic frequency observed was AA 8.5%, AG 57.4% and GG 34.1%. Both the G allele as the GG and AG genotypes were significantly higher in the obese group compared to the other groups (p < 0.001). CONCLUSION: A higher prevalence of the G allele was observed in elderly obese group, responsible for encoding an abnormal enzyme and consequent reduction of antioxidant defenses, which contribute to inflammation process and obesity in the elderly.
RESUMO INTRODUÇÃO: A obesidade está relacionada com a possibilidade de numerosos danos metabólicos associados ao estresse oxidativo. As enzimas da família glutationa S-transferase (GST) têm como função promover a detoxificação, entretanto, polimorfismos no gene da glutationa S-transferase P1 (GSTP1) geram alelos menos eficientes, bem como diminuição da sua quantidade e atividade. OBJETIVO: Este estudo teve como objetivo analisar a frequência dos alelos (A e G) e dos genótipos do polimorfismo Ile105Val do gene GSTP1, além de sua associação à obesidade em idosos. MATERIAIS E MÉTODOS: Tratou-se de um estudo transversal, o qual envolveu 232 indivíduos com idades entre 60 e 98 anos, de ambos os sexos, oriundos da região Sul do Brasil. Os voluntários foram caracterizados de acordo com o índice de massa corporal (IMC) em três grupos: peso normal (n = 52), sobrepreso (n = 133) e obesos (n = 47). A antropometria foi avaliada, e a técnica de reação em cadeia da polimerase-polimorfismo no comprimento de fragmentos de restrição (PCR-RFLP) foi usada para análise genética a partir de amostras de sangue periférico. RESULTADOS: A frequência alélica no grupo de idosos obesos foi de 37,2% para o alelo A e 62,8% para o G, e a frequência genotípica observada, de AA 8,5%, AG 57,4% e GG 34,1%. Tanto o alelo G quanto os genótipos GG e AG foram significativamente maiores no grupo obeso quando comparados com os dos demais grupos (p < 0,001). CONCLUSÃO: Observou-se maior prevalência do alelo G no grupo de idosos obesos, responsável pela codificação de uma enzima anormal e consequente diminuição das defesas antioxidantes, que contribuem para o processo inflamatório e a obesidade em idosos.
