RESUMO
OBJECTIVE: The aim of this study was to analyze the frequencies of the CCR5 delta 32 deletion and HLA class II alleles in Mexican Amerindian populations and its relevance in the development and severity of RA. METHODS: We studied 212 Mexican Mestizo subjects (40 patients with refractory RA, 102 patients with non-refractory RA and 70 healthy individuals). At the same time, to evaluate the ethnicity of the CCR5 delta 32 deletion we also studied 192 individuals from three Mexican Amerindian populations (70 Mayo (Capomo) individuals, 61 Teenek individuals, and 61 Mazatecan Indians). The delta 32 deletion in the CCR5 structural gene and HLA-DRB1 were determined by a PCR-SSP and a PCR-SSO procedure, respectively. RESULTS: In the non-refractory RA group the CCR5 delta 32 gene frequency was 0.019 and the following genotype frequencies were observed: CCR5/CCR5 = 98.0%, CCR5/CCR5 delta 32 = 1.9% and CCR5 delta 32/CCR5 delta = 1.0%. In the refractory RA group the CCR5 delta 32 gene frequency was 0.025 and the genotype distribution was similar to that in the non-refractory RA group. The deletion was not detected in the Mexican Mestizo healthy group, or among the Teenek and Mayo Amerindians, all being individuals homozygous for the wild type allele. In the Mazatecan group the deletion frequency was 1.6% (g.f. = 0.016). We observed a significant increase in the frequency of the DRB1*07 allele in severe RA patients in relation to the non-severe RA group (p = 0.02, OR = 5.65, 95% CI = 0.95-43.05). CONCLUSION: Our results suggest that the CCR5 delta 32 deletion is not common in Mexican Amerindian populations and this study does not support an important role of CCR5 delta 32 in the pathogenesis of RA or a severe form of the disease in Mexicans.
Assuntos
Artrite Reumatoide/genética , Predisposição Genética para Doença , Hispânico ou Latino/genética , Polimorfismo Genético , Receptores CCR5/genética , Adulto , Idoso , Artrite Reumatoide/fisiopatologia , Sequência de Bases , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Frequência do Gene , Genótipo , Antígenos HLA-DR/análise , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Razão de Chances , Reação em Cadeia da Polimerase , Probabilidade , Valores de Referência , Estudos de Amostragem , Índice de Gravidade de DoençaRESUMO
The development of thermoregulation in newborns is delayed by prenatal alcohol exposure in an animal model of moderate maternal drinking. Newborn mammals generate heat primarily via nonshivering thermogenesis in brown adipose tissue (BAT), which is activated by the sympathetic nervous system. In this study, the effects of prenatal alcohol exposure on the development of the sympathetic innervation of BAT was investigated by assessing the concentration of norepinephrine (NE) in interscapular BAT. Pregnant dams were given either a liquid diet with 35% of the calories derived from alcohol, a liquid diet without alcohol to control for any effects of the liquid diet administration, or ad libitum food and water. Interscapular brown adipose tissue was excised from 5-, 10-, and 20-day-old male and female offspring. At 5 days of age, alcohol-exposed pups had significantly lower NE concentrations than did pups in either control group. However, 20-day-old alcohol-exposed pups had significantly higher NE concentrations than either control group. These results suggest a delay in the development of the sympathetic activation of BAT thermogenesis, followed by a compensatory overactivation. These findings may have important implications for understanding the mechanisms underlying thermoregulatory deficits seen after prenatal alcohol exposure. In addition, these results suggest that maternal alcohol consumption may increase the risk of sudden infant death syndrome, which has been linked to inappropriate BAT thermogenesis.
