title: Association between RAPH1 Gene Haplotypes and CHE2 Locus Phenotypes.
abstract: The human butyrylcholinesterase (BChE) is a serum esterase that has been associated with body mass index (BMI) and obesity. Its activity is conditioned by alleles of BCHE gene and the CHE2 locus that codifies an unknown BChE-binding protein (C5 complex). The hypothesis that the CHE2 locus is the RAPH1 gene, which encodes lamellipodin (Lpd), was raised in a study that observed Lpd peptides released from denatured BChE tetramers. The aim of this study was to test this hypothesis by evaluating SNPs of RAPH1 gene (rs2246118:C > T, rs3814365:A > G and rs2465520:C > T) in 34 CHE2 C5+ and 92 CHE2 C5- individuals, corresponding to the presence and absence of C5 complex. The results showed association of two haplotypes (CAC and TGC) with CHE2 C5+ phenotype. RAPH1 haplotypes was also associated with intense (TGC) and faint (CAC) CHE2 C5+ phenotypes. BChE activity was higher in intense CHE2 C5+ than faint CHE2 C5+ phenotype. Our results corroborate the hypothesis that the RAPH1 gene is the CHE2 locus and suggest that the variable expressivity of the CHE2 C5+ phenotypes is, at least in part, due to its genetic heterogeneity, which is leading to increased BChE activity only in individuals with intense CHE2 C5+ phenotype.
authors.affiliation: Polymorphism and Linkage Laboratory, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil.
authors.forename: Fabiana
authors.initials: F
authors.lastname: A De Andrade
authors.affiliation: Polymorphism and Linkage Laboratory, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil.
authors.forename: Meire S
authors.initials: MS
authors.lastname: Batistela
authors.affiliation: Polymorphism and Linkage Laboratory, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil.
authors.forename: Sarah Da C
authors.initials: Sda C
authors.lastname: Amaral
authors.affiliation: Polymorphism and Linkage Laboratory, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil.
authors.forename: Willian
authors.initials: W
authors.lastname: Dos Santos
authors.affiliation: Faculdades Integradas do Brasil, Curitiba, Paraná, Brazil.
authors.forename: Liya R
authors.initials: LR
authors.lastname: Mikami
authors.affiliation: Polymorphism and Linkage Laboratory, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil.
authors.forename: Eleidi A
authors.initials: EA
authors.lastname: Chautard-Freire-Maia
authors.affiliation: Polymorphism and Linkage Laboratory, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil.
authors.forename: Lupe
authors.initials: L
authors.lastname: Furtado-Alle
authors.affiliation: Polymorphism and Linkage Laboratory, Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil.
authors.forename: Ricardo L R
authors.initials: RL
authors.lastname: Souza
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002802:Cholinesterases / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C493339:RAPH1 protein, human; C116697:cholinesterase 2; D002802:Cholinesterases
keywords: BCHE gene; CHE2 locus; RAPH1 gene; butyrylcholinesterase; lamellipodin