Rat Receptor-associated Protein [Myc]

BACKGROUND: Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimer's disease (AD). OBJECTIVES: We attempted to assess the relationship between early-life lead exposure and potential biomarkers for AD among young men and women. We also attempted to assess whether early-life lead exposure was associated with changes in expression of AD-related genes. METHODS: We used sandwich enzyme-linked immunosorbent assays (ELISA) to measure plasma concentrations of amyloid beta proteins A beta(40) and A beta(42) among 55 adults who had participated as newborns and young children in a prospective cohort study of the effects of lead exposure on development. We used RNA microarray techniques to analyze gene expression. RESULTS: Mean plasma A beta(42) concentrations were lower among 13 participants with high umbilical cord blood lead concentrations (>= 10 mu g/dL) than in 42 participants with lower cord blood lead concentrations (p = 0.08). Among 10 participants with high prenatal lead exposure, we found evidence of an inverse relationship between umbilical cord lead concentration and expression of ADAM metallo peptidase domain 9 (ADAM9), reticulon 4 (RTN4), and low-density lipoprotein receptor-related protein associated protein 1 (LRPAP1) genes, whose products are believed to affect A beta production and deposition. Gene network analysis suggested enrichment in gene sets involved in nerve growth and general cell development. CONCLUSIONS: Data from our exploratory study suggest that prenatal lead exposure may influence A beta-related biological pathways that have been implicated in AD onset. Gene network analysis identified further candidates to study the mechanisms of developmental lead neurotoxicity.

Introduction: To identify high risk alleles for gallstone disease, we analyzed association of LDLR AvaII, LRPAP1 insertion/deletion, CETP TaqI B, and LPL HindIII polymorphisms with gallstone disease. Methods: In DNA samples of 214 gallstone patients and 322 age and sex matched controls, specific region containing polymorphisms was PCR amplified and digested with restriction enzymes except for LRPAP1 insertion/deletion polymorphism. Results: LRPAP1 gene insertion/deletion polymorphism was found to be significantly associated with gallstone disease. Genotype 11 was conferring significant risk for gallstone disease in females only (P = 0.019; OR 2.577, 95% CI 1.144-5.806). LDLR AvaII, CETP TaqI B, and LPL HindIII polymorphisms were not found to be associated with gallstone disease either at genotype or allele level. Conclusions: LRPAP1, II genotype carrier females may have increased risk for gallstone disease. On the other hand, LDLR AvaII, CETP TaqI B, and LPL HindIII polymorphisms may not be associated with gallstone disease. (c) 2006 Elsevier Ireland Ltd. All rights reserved.