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.