RESUMO
OBJECTIVES: We hypothesized that common variation in the angiotensinogen (AGT), beta-3-adrenergic receptor. intestinal fatty acid-binding protein, serum paraoxonase, paraoxonase-2, hepatic lipase, apolipoprotein E (APOE), and Werner helicase (WRN) genes would be associated with variation in biochemical phenotypes in a previously unstudied neonatal sample. DESIGN AND METHODS: We examined associations of both nongenetic and genetic variables with plasma lipoprotein traits in neonates from Trinidad. RESULTS: Among nongenetic variables, we found significant associations between plasma concentrations of 1.) lipoprotein (a) [Lp(a)] and both ethnicity (p=0.037) and birth weight (p=0.001); 2)total cholesterol and gender (p=0.010); 3)triglyceride and birth weight (p=0.035); and 4)apolipoprotein A1 and gender (p=0.016). Among genetic variables, we found that: 1)common variation on chromosome 1q in AGT codon 235 was significantly associated with variation in plasma apolipoproteins Al (p<0.0001); and 3)common variation in APOE at codons 112 and 158 was significantly associated with variation in plasma triglycerides (p=0.013). CONCLUSIONS: The associations with AGT and WRN are novel and may have resulted either from direct influence of the genetic variants or through linkage disequilibrium with other functional loci, such as the familial combined hyperlipidemia locus on chromosome 1q in the case of AGT. Despite the fact that there are some limitations in making determinations from cord blood, the results suggest that there may be genetic determinants of plasma lipoproteins in neonates. (AU)
Assuntos
Lactente , Feminino , Humanos , Masculino , Lipoproteínas/sangue , Lipoproteínas/genética , África , Alelos , Angiotensinogênio/genética , Apolipoproteínas E/genética , Ásia , Proteínas de Transporte/genética , DNA Helicases/genética , Esterases/sangue , Esterases/genética , Frequência do Gene , Genética Populacional , Lipase/genética , Proteína P2 de Mielina/genética , Fenótipo , Receptores Adrenérgicos beta/genética , Trinidad e Tobago/etnologia , Variação GenéticaRESUMO
Variation in the PON1 and PON2 genes has been shown to be associated with coronary heart disease risk in adults of South Asian origin. In this group, low birth weight is also associated with coronary heart disease risk. We therefore hypothesized that variation in PON1 and PON2 genes may be associated with variation in birth weight. This relationship was examined in 90 consecutive Trinidadian neonates of different ethnic origins. We found that variation in PON2 was significantly associated with variation in birth weight in Trinidadian neonates of south Asian origin. Among the neonates of South Asian origin, those who were homozygous for PON A148/A148 had significantly lower birth weight, by approximately 00 g, compared with those with the other two genotypes (P < 0.05). For neonates of south Asian origin, PON2 A148/A148 homozygotes were significantly more prevalent in those comprising the lowest tertile for birth weight than those comprising the highest tertile (0.41 versus 0.24, P < 0.05). There were no significant associations of PON variation with any phenotype in other ethnic groups. We conclude that among neonates of South Asian origin, homozygosity for PON2 A148/A148, is associated with significantly lower birth weight. This suggests that genetic factors in the fetus may be important determinants of neonatal birth weight and possibly of more distal adult phenotypes, such as coronary heart disease.(AU)
Assuntos
Adulto , Humanos , Recém-Nascido , Peso ao Nascer/genética , Esterases/genética , Alelos , Ásia/etnologia , Doença das Coronárias/genética , Frequência do Gene , Genótipo , Desequilíbrio de Ligação , Fenótipo , Trinidad e TobagoRESUMO
Histochemical changes in the liver of rats, treated with the pyrrolizidine alkaloidal constituent of Crotalaria fulva, indicated primarily damage of the hepatic parenchymal cells. The observed differences in activity of enzymes suggested functional inpairment of the cell membrane, mitochondria, endoplasmatic reticulum, and lysosomes in the liver cells. In large doses, fulvine produced a hyaline droplet degeneration in the epithelium of the proximal convoluted tubules of the kidney. Stability of the mitochondrial and changes in activity of the lysosomal enzymes would imply a functional adaptation, rather than primary damage of the epithelium.(AU)
