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- W150498003 abstract "Natriuretic peptides (NP) undergo enzymatic hydrolysis catalyzed by membrane metallo-endopeptidase (MME). Genetic variation in MME has not been addressed by resequencing the gene in different ethnic populations. DNA samples from 96 Caucasian American, 96 African American, and 96 Han Chinese American subjects, part of the “Human Variation Panel” were obtained from the Coriell Cell Repository and were resequenced. Ninety polymorphisms were identified in the 3 ethnic groups, including 8 nonsynonymous single nucleotide polymorphisms (SNP) that resulted in the following changes in encoded amino acids: Met(8)Val, Arg(23)Pro, Met(73)Val, Gly(225)Ala, Asn(285)Ser, Val(345)Ile, Met(419)Leu, and Asn(593)Ser. Among the 90 polymorphisms observed, 65 were novel and 7 of the 8 nonsynonymous SNPs had not been previously described. COS-1 cells were transfected with variant MME expression constructs and MME activity was measured by a one-step fluorometric assay using N-dansyl-Ala-Gly-D-nitro-Phe-Gly as a substrate. The same recombinant enzymes were analyzed by quantitative Western blot analysis. There were significant differences for two variant allozymes (Val73 and Ser285) in levels of enzyme activity and immunoreactive protein as compared to (wild type) WT, as shown in Figure. These studies have identified 2 SNPs that alter the expression and activity of MME. These variant SNPs could have a significant effect on the metabolism of NP." @default.
- W150498003 created "2016-06-24" @default.
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- W150498003 date "2010-04-01" @default.
- W150498003 modified "2023-09-23" @default.
- W150498003 title "Natriuretic Peptide Pharmacogenomics: Common Gene Sequence Variation and Functional Characterization of Membrane Metallo‐Endopeptidase (MME)" @default.
- W150498003 doi "https://doi.org/10.1096/fasebj.24.1_supplement.756.1" @default.
- W150498003 hasPublicationYear "2010" @default.
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