Association of variants of the -116 site of the butyrylcholinesterase BCHE gene to enzyme activity and body mass index.
Butyrylcholinesterase (BChE) is coded by the BCHE gene that presents four exons. The non-codifying exon 1 presents two variants -116G and -116A, being -116A preferentially in cis conformation with the 539T variant (K) of exon 4 which was associated with lower BChE activity and lower body mass index (BMI) variance. This study analyzed the frequency of -116 variants and the relation of genotypes -116GG;539AA, -116GG;539AT and -116GA;539AT with BChE activity and with BMI in Euro-Brazilian blood donors. The frequency of -116A was significantly higher (18.9%) in the low BChE activity group when compared to obese (8.6%) and normal BMI (9.3%) groups. In obese and non-obese groups, the -116GA;539AT genotype showed significantly lower mean BChE activity when compared to the -116GG;539AA genotype and in obese individuals the -116GA;539AT genotype also showed lower BChE activity than the -116GG;539AT genotype. In a sample selected independently of BMI, the -116GA;539AT genotype showed significantly higher BMI variance (21.75) when compared to -116GG;539AA (12.14) and to -116GG;539AT (13.43) genotypes, indicating that the association with higher BMI variance only occurs in the presence of the -116A variant. In the obese sample, the -116GG;539AT genotype presented mean (32.1+/-0.3) and variance (2.3) of BMI significantly lower than those found in the -116GG;539AA (33.0+/-0.3 and 9.9, respectively) and -116GA;539AT (33.7+/-0.7 and 12.2, respectively) genotypes. These data show that: (1) the K (539T) variant alone is not associated with decreased BChE activity, being the 5' UTR -116A variant necessary for this decrease, probably by affecting transcription and/or translation of the BCHE gene; (2) samples with different BMI distributions present different relationships between BCHE genotypes and BMI, reinforcing the hypothesis of a role for the BCHE gene in BMI determination.
Furtado-Alle
Lupe
L
Department of Genetics, Federal University of Paraná, Brazil.
Andrade
Fabiana A
FA
Nunes
Kelly
K
Mikami
Liya R
LR
Souza
Ricardo L R
RL
Chautard-Freire-Maia
Eleidi A
EA
D001483:Base Sequence; D015992:Body Mass Index; D002091:Butyrylcholinesterase / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D017931:DNA Primers; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation; D009765:Obesity / Q000097:blood / Q000201:enzymology
D017931:DNA Primers; D002091:Butyrylcholinesterase