Obesity and variants of the GHRL (ghrelin) and BCHE (butyrylcholinesterase) genes

Ghrelin coded by the GHRL gene is related to weight-gain, its deactivation possibly depending on its hydrolyzation by butyrylcholinesterase (BChE) encoded by the BCHE gene, an enzyme already associated with the body mass index (BMI). The aim was to search for relationships between SNPs of the GHRL and BCHE genes with BChE activity, BMI and obesity in 144 obese and 153 nonobese Euro-Brazilian male blood donors. In the obese individuals, a significant association with higher BChE activity, in the 72LM+72MM; –116GG genotype class (GHRL and BCHE genes, respectively) was noted. No significant differences were found otherwise, through comparisons between obese and control individuals, of genotype and allele frequencies in SNPs of the GHRL gene (Arg51Gln and Leu72Met), or mean BMI between 72LL and 72LM+72MM genotypes. Although there appears to be no direct relationship between the examined GHRL SNPs and BMI, the association of the 72M SNP with higher BChE activity in obese subjects probably points to a regulatory mechanism, thereby implying the influence of the GHRL gene on BChE expression, and a consequential metabolic role in the complex process of fat utilization

Molecular forms of butyrylcholinesterase and obesity

This study compared obese (N = 134) and unobese (N = 92) male blood donors, regarding the relative intensity (RI) and activity of different molecular forms (G1, G2, G4 and G1-ALB) of butyrylcholinesterase (BChE, EC 3.1.1.8) found in plasma, thereby searching for an association between these variables with obesity and SNPs of exons 1 and 4 of the BCHE gene. It was shown that obese and unobese individuals do not differ in the RI of each BChE band, even when classifying the sample into three genotypes of exons 1 and 4 of the BCHE gene (-116GG/539AA, -116GG/539AT, -116GA/539AT). Although the mean BChE activity of each band was significantly higher in obese than in unobese blood donors, the proportions of BChE bands were maintained, even under the metabolic stress associated to obesity, thereby leading to infer that this proportion is somehow regulated, and may therefore be important for BChE functions

Investigation of Association between Susceptibility to Leprosy and SNPs inside and near the BCHE Gene of Butyrylcholinesterase

Leprosy is a chronic disease caused by Mycobacterium leprae and affects the skin and the peripheral nervous system. Butyrylcholinesterase is coded by the BCHE gene, and the atypical allele (70G; rs1799807) has been investigated as a leprosy risk factor, with conflicting results. The present study estimated the frequencies of variants of rs1799807 and of five additional SNPs at the BCHE gene or near it: rs1126680, rs1803274, rs2863381, rs4440084, and rs4387996. A total of 167 patients and 150 healthy controls were genotyped by TaqMan PCR. Significantly higher allelic (70G) and genotypic (70DG) frequencies in rs1799807 were found in the patient group, with odds ratio (OR) of 6.33 (1.40 to 28.53) for the heterozygote. This finding was replicated in a comparison of the cases against a control group of 361 blood donors. The present data suggest that the atypical BChE variant may predispose to leprosy per se

The Variable Expression of the C4/5 Complex of Human Butyrylcholinesterase and Body Mass Index

The activity of a supposedly heteromeric complex (C4/5) of butyrylcholinesterase (BChE; EC 3.1.1.8) was analyzed in relation to body mass index (BMI). The activities of the C4/5 and COF (other molecular forms) bands in CHE2 C5– (n = 447) and CHE2 C5+ (n = 88) individuals were quantified by densitometry. Since the absolute activity of C4/5 (AC4/5) showed the highest correlation coefficient with weight in the CHE2 C5– phenotype when compared to the other BChE activity variables (total, relative C4/5, and absolute COF), this variable was used for the classification of 51 CHE2 C5– individuals into three groups (low, average, and high), paired by sex, age, and ethnic origin. The low AC4/5 group was found to present a significantly (p \u3c 0.0001) lower mean BMI (22.9) than the other groups (average = 25.2, and high = 26.3). In the CHE2 C5+ individuals no statistically significant standardized regression coefficient was verified between BMI (dependent variable) and the C4/5 band activities. These data show that the behavior of the C4/5 band in relation to BMI differs between the CHE2 C5– and CHE2 C5+ phenotypes. While the C5 band of the CHE2 C5+ individuals is negatively associated with fat storage in the adipose cells, the present data show that the C4/5 band is positively associated with this storage in the CHE2 C5– phenotype

Association of the CHE2 Locus with Body Mass Index and Butyrylcholinesterase Activity

The butyrylcholinesterase (BChE; EC 3.1.1.8) activities of two electrophoretic bands of the CHE2 C5+ phenotype—C5 and COF (other forms)—were quantified by densitometry in 100 individuals. The activity data suggested that, in addition to determining C5, the CHE2*C5+ allele also increases the level of other BChE forms. Since the relative activity of C5 showed the highest correlation coefficient with weight when compared with the other BChE activity variables (total, absolute C5, and absolute COF), its median activity level was used for the classification of CHE2 C5+ phenotypes (faint and intense). Mean body mass index (BMI) was compared among the CHE2 locus phenotypes—controlled by sex, age, and ethnic group. It was shown that the intense CHE2 C5+ phenotype presents a significantly lower ( p \u3c 0.001) mean BMI (23.2) than the other phenotypes (faint CHE2 C5+ = 25.2; CHE2 C5– = 25.4). It seems that the relative COF activity is positively associated with fat storage, since CHE2 C5– and faint CHE2 C5+ phenotypes showed higher mean BMI than the intense CHE2 C5+ phenotype. Our hypothesis is that the presence of C5 in a relatively high proportion leads to less fat storage

Butyrylcholinesterase genetic variability in Guarani Amerindians from the Brazilian state of Mato Grosso do Sul

Human butyrylcholinesterase (BChE; EC 3.1.1.8) is a polymorphic enzyme coded by the BCHE gene (3q26.1-q26.2) while the CHE2 gene (2q33-q35) determines a still not characterized substance that forms a complex with BChE (C5), being the CHE2 C5+ and CHE2 C5- phenotypes detected in electrophoresis. The present study investigated BCHE and CHE2 variability and the BChE activity of Brazilian Guarani Amerindians from the Kaiowá and Ñandeva sub-groups living in several indigenous territories in the Brazilian state of Mato Grosso do Sul. The frequency of the BCHE exon 2 D70G (A) allele was 0.60% ± 0.35% while that of the BCHE exon 2 G390V (F-2) allele, never before screened in Amerindians, was 8.82% ± 1.35%. This is the first time that the BCHE gene exon 4 A539T (K) allele has been surveyed in Brazilian Amerindians where it was found at a frequency of 3.69% ± 0.85%, similar to that found in Chilean Mapuche Amerindians. The BCHE gene variability seen in this survey differs from that of non-isolated populations in respect to both A539T and G390V allele frequency. The CHE2 C5+ phenotype frequency was 14.40% ± 2.22% and falls within the range of that found for other Brazilian Amerindian samples

Absence of the -116A variant of the butyrylcholinesterase BCHE gene in Guarani Amerindians from Mato Grosso do Sul

Butyrylcholinesterase (BChE; EC 3.1.1.8; Online Mendelian Inheritance in Man (OMIM) number 177400) is an enzyme found in many human tissues and encoded by the BCHE gene, of which 65 variants have been identified. In a recent study we found that the -116A variant of exon 1 of the BCHE gene was associated with lower mean BChE activity. The present study analyzed the -116 single nucleotide polymorphism (SNP) in 253 Guarani Amerindian Brazilians from the state of Mato Grosso do Sul (148 Guarani-Kaiowá, 83 Guarani-Ñandeva and 22 Kaiowá-Ñandeva descendants) and verified that they were all homozygotic for the -116G variant. A comparative analysis of the -116 site in nine vertebrate species indicated the -116A variant as the ancestral type. This is the first study of the -116 SNP in Amerindians and it is therefore difficult to infer whether or not the -116A variant was always absent from southern paleo-Amerindians or was present and then subsequently lost due to evolutionary factors