RESUMEN
Cholinergic neurons have been implicated in depression and in the disorders of REM sleep in depression. We examined a common A-> T 1890 polymorphism in the 3' UTR of the cholinergic muscarinic receptor 2 (CHRM2) gene. There was a significant increase in the frequency of 11 homozygotes in 126 women with major depression (43.7%) compared to 304 women without major depression (25.7%), P =.001. There was no increase in the frequency of 11 homozygotes in 52 men with depression (26.9%) compared to 278 men without depression (27.7%). Regression analysis, scoring subjects with the 11 genotype as 1, and those with other genotypes as 0, showed that in women r(2) =.030, F = 13.37, P =.0003. By contrast, in men r(2) =.00001, F = 0.002, P =.96. These results are consistent with a gender-specific role of the CHRM2 gene in depression in women.
Asunto(s)
Trastorno Depresivo Mayor/genética , Receptores Muscarínicos/genética , Adulto , Alelos , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Receptor Muscarínico M2 , Factores SexualesRESUMEN
The activity of human phenylethanolamine N-methyltransferase (PNMT) is reduced in the neurons of those cells in many subcortical areas of the brain that are known to undergo neurodegeneration in Alzheimer disease (AD). Others have reported that PNMT is decreased in brains of persons with AD and that the decrease in enzymatic activity is due to a reduced amount of the enzyme protein. We have previously described two polymorphisms, G-353A and G-148A, in the promoter region of the gene coding for PNMT. These markers were tested for their association with the occurrence of sporadic AD. Genotyping of 131 necropsy confirmed AD cases, and 947 adult nondemented controls were completed. We observed a significant association between both of the PNMT gene polymorphisms and early-onset AD (EOAD) (P < or = 0.007), but not in late-onset AD (LOAD). These data suggest that genetic variation in the promoter of the PNMT gene is associated with increased susceptibility to the sporadic form of EOAD.
Asunto(s)
Enfermedad de Alzheimer/genética , Feniletanolamina N-Metiltransferasa/genética , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Alelos , Enfermedad de Alzheimer/patología , ADN/genética , Frecuencia de los Genes , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo Genético , Regiones Promotoras Genéticas/genéticaRESUMEN
Functional studies assessed the cytolytic activity of the amino terminal peptide (FP-I; 23 residues 519-541) of the glycoprotein 41,000 (gp41) of the Human Immunodeficiency Virus Type-1 (HIV-1). Synthetically prepared FP-I efficiently hemolyzed human red blood cells at 37 degrees C, with 40% lysis at 32 microM. Kinetic studies indicated that FP-I induced maximal hemolysis in 30 min, probably through tight binding of the peptide with the red cell membrane. The Phe-Leu-Gly-Phe-Leu-Gly (residues 526-531) motif in FP-I apparently plays a critical role in lysis of red cells, since no hemolytic activity was observed for an amino-acid-substituted FP-I in which the unique Phe-Leu-Gly-Phe-Leu-Gly was converted to Ala-Leu-Gly-Ala-Leu-Gly. As neither smaller constituent peptides (e.g., residues 519-524 and residues 526-536) nor a N-terminal flanking peptide (e.g., residues 512-523) induced red cell hemolysis, the entire 23-residue (519-541) sequence of FP-I may be required for hemolytic activity. FP-I was also cytolytic with CD4(+)-bearing Hut-78 cells, with 40% lysis at approx. 150 microM. These results are consistent with an earlier hypothesis that the N-terminal peptide of gp41 may partially contribute to the in vivo cytopathic actions of HIV-1 infection (Gallaher, W.R. (1987) Cell 50, 327-328).