Butyrylcholinesterase and lipid metabolism: Possible dual role in metabolic disorders.

Butyrylcholinesterase (BChE), an enzyme primarily found in the liver, plasma, and brain, has been recognized for its role in the hydrolysis of choline esters. Recent studies have shed light on its involvement in lipid metabolism, revealing its potential as a crucial player in maintaining lipid homeostasis. However, the interactions between external factors and BChE activity in lipid metabolic pathways remain a complex subject of study. This review summarizes the current knowledge regarding BChE activity and lipid metabolism and seeks to clarify the nature of this relationship as causal or consequential. Evidence supports the role of BChE in energy homeostasis disruption, such as obesity and related metabolic disorders, where it exhibits lipolytic activity and mediates fatty acid use and storage. The unexpected functions of BChE in lipoprotein synthesis and the impact of polymorphic variants of the BCHE gene suggest a central role in lipid metabolism; however, further investigation is needed to confirm and describe these functions, especially considering the metabolic context. Furthermore, exploring therapeutic interventions in lipid metabolism disorders contributes to elucidating their implications on BChE activity, but attention to the metabolic status and genotypes as possible factors in this interaction is needed. In summary, further research in this field holds promise for improving our understanding of the complex interplay between BChE and lipid metabolism, and its potential clinical applications. However, the available data corroborate the dual role of BChE activity, both as a critical responsive element to metabolic challenges and as a predisposition factor to metabolic diseases.

Olive oil increases the LIPC expression when associated with an Eastern pattern diet: An experimental study with Wistar rats.

Some nutrigenomic effects of extra virgin olive oil (EVOO) are described in the literature; however, it is unknown whether its interaction with lipid-related genes is independent of the combined diet. In this sense, our objective was to investigate whether EVOO consumption associated with Western or Eastern human-based chow modulates the expression of APOE, APOB, and LIPC genes in rats. In view of this, the hypothesis is that the consumption of olive oil may not have the same nutrigenomic effects, depending on the diet consumed. For this study, 56 female rats were randomly divided into four groups: Western diet with EVOO (WS), Western-diet control (WC), Eastern-diet with EVOO (ES), and Eastern-diet control (EC). After 15 weeks, the animals were anesthetized with an intraperitoneal injection of chloral hydrate 15% (1.5 mL/kg) and euthanized by guillotining, and adipose tissue, liver, and blood were extracted. Triglycerides, cholesterol, and glucose levels were obtained following standard protocols, and relative gene expressions were calculated using the ΔΔCt method after quantitative PCR. The EVOO consumption was associated with LIPC gene expression increase in the liver only in animals fed the Eastern diet, compared to EC and WS animals. The EVOO consumption, combined with the Eastern diet, was associated with decreased triglyceride levels compared to WC. Although final weight and weight gain were similar between groups, WS animals had lower daily energy consumption. Conclusion: Given these results, the authors suggested that the EVOO nutrigenomic effects were restricted to an Eastern human-based diet.

Animal model of Alzheimer's disease induced by streptozotocin: New insights about cholinergic pathway.

Alzheimer's disease (AD) is of multifactorial origin, and still presents several gaps regarding its development and progression. Disorders of the cholinergic system are well known to be involved in the pathogenesis of AD, characterized by increased acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and decreased acetyltransferase (ChAT) enzymatic activities. Late onset AD (LOAD) animal model induced by intracerebroventricular injection of streptozotocin (icv-STZ) showed promising results in this context, due to the similarity with the pathophysiology of human LOAD. Thus, this study aimed to assess the long-term effects of icv-STZ on the cholinergic system, through the measuring of AChE and BChE enzymatic activities in hippocampus, prefrontal cortex and liver of animals euthanized 30 and 120-days after the icv-STZ. Regarding the cholinergic response to icv-STZ, the 30-days and 120-days STZ-induced rats exhibit decreased AChE and BChE activities only in the hippocampus. The cognitive deficit was more consistent in the 30-days post icv-STZ animals, as was the weight loss. This is the first study to investigate the long-term effects (more than 60 days) of the icv-STZ on AChE and BChE activities, and our results, as well as those of a recent study, suggest that the cholinergic system may not be compromised by icv-STZ, at least in the long term, which means that this model may not be the best model for studying the cholinergic system in AD or that it is informative only for a short period.

BChE inhibitors from marine organisms - A review.

Acetylcholine is a key neurotransmitter for brain and muscle function, that has its levels decreased in the brain of people with Alzheimer's Disease (AD). Cholinesterase inhibitors are medicines that decrease the breakdown of acetylcholine, through the inhibition of acetyl- and butyrylcholinesterase enzymes. Despite the fact that butyrylcholinesterase activity rises with the disease, while acetylcholinesterase activity declines, the cholinesterase inhibitors that are currently commercialized inhibit either acetylcholinesterase or both enzymes. The development of selective butyrylcholinesterase inhibitors is a promising strategy in the search for new drugs acting against AD. The marine environment is a rich source of molecules with therapeutic potential, which can provide compounds more easily than traditional methods, with reduced toxicity risks compared to synthetic molecules. This review comprises articles from 2003 to 2020, that assessed the butyrylcholinesterase inhibitory activities from marine organisms, considering their crude extracts and isolated compounds. Part of the articles reported a multi-target activity, inhibiting also other AD-related enzymes. Some of the marine compounds reported here have shown an excellent potential for butyrylcholinesterase inhibition compared to standard inhibitors. Further studies of some compounds reported here may lead to the development of a new treatment for AD.

ADRB2 gene influences responsiveness to physical exercise programs: A longitudinal study applied to overweight or obese Brazilian children and adolescents.

We aimed to investigate whether the expression levels and polymorphisms in the ADRB2 gene have influenced the anthropometric and cardiometabolic outcomes changes in obese/overweight children submitted to physical exercise programs. This longitudinal study included 197 overweight or obese children aged 10-16 years, submitted to physical exercise programs - three sessions per week for 12 weeks. Anthropometric and cardiometabolic profile was collected before and after interventions. The ADRB2 gene expression levels were also measured in these two moments in a small intervention group (n = 17) and a control group (n = 18). Arg16Gly and Gln27Glu polymorphisms were genotyped. A positive correlation between ADRB2 expression and loss of body fat (%) (p = 0.038) was observed, which remained after sex and BMI change corrections. Carriers of the Glu27Glu genotype presented a better response to physical exercise programs regarding their triglycerides levels and triglyceride-glucose index (p = 0.001 for both). The participants' responsiveness to physical exercise programs showed variation due to the ADRB2 gene expression and the Gln27Glu polymorphism. A more significant loss of body fat was associated with higher levels of ADRB2 expression, and the Glu27Glu genotype was associated with a better cardiometabolic response. The Arg16Gly polymorphism did not show interaction with the responsiveness to physical exercise.

Influence of a genetic variant of CHAT gene over the profile of plasma soluble ChAT in Alzheimer disease.

The choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) are fundamental to neurophysiological functions of the central cholinergic system. We confirmed and quantified the presence of extracellular ChAT protein in human plasma and also characterized ChAT and VAChT polymorphisms, protein and activity levels in plasma of Alzheimer's disease patients (AD; N = 112) and in cognitively healthy controls (EC; N = 118). We found no significant differences in plasma levels of ChAT activity and protein between AD and EC groups. Although no differences were observed in plasma ChAT activity and protein concentration among ChEI-treated and untreated AD patients, ChAT activity and protein levels variance in plasma were higher among the rivastigmine-treated group (ChAT protein: p = 0.005; ChAT activity: p = 0.0002). Moreover, AD patients homozygous for SNP rs1880676 A allele exhibited higher levels of ChAT activity. Considering this is the first study to report the influence of genetic variability of CHAT locus over ChAT activity in AD patients plasma, it opens a new set of important questions on peripheral cholinergic signaling in AD.

Is it possible ABC transporters genetic variants influence the outcomes of a weight-loss diet in obese women?

ATP-Binding Cassette (ABC) transporters are involved in cholesterol metabolism and their dysfunctions could lead to obesity-associated complications. It was investigated whether SNPs in the ABCA1 (rs1800977 and rs2230806), ABCA7 (rs2279796) and ABCG1 (rs692383 and rs3827225) genes can modulate the responsiveness of 137 obese women to a weight-loss dietary intervention. Thus, anthropometric and lipid profiles were collected at baseline and after nine weeks of a calorie-restricted diet of 600kcal per day and participants were genotyped for the ABC genes SNPs. Regarding the transversal analysis, the ABCA7 rs2279796 GG genotype was associated with higher levels of total cholesterol and LDL-c at baseline (p = 0.044 for both). Association between ABCG1 rs692383 AA genotype and lower BMI were found in the post-diet moment, however, statistical significance was lost after multi-test correction. Regarding the longitudinal analysis, after multi-test correction, the association remained between ABCG1 rs692383 G allele and HDL-c levels: G allele carriers had a lower HDL-c reduction (p = 0.043). Results suggest the standard weight-loss diet applied in this study could attenuate the ABCA7 rs2279796 GG genotype effects found at baseline and non-dyslipidemic obese women with ABCG1 rs692383 G allele are benefitting from the diet with a lower reduction in HDL-c levels.

IL18 Gene Polymorphism Influences Age of Onset of DM1 in African Ancestry Brazilians.

The aim of this study was to investigate the relationship of two single nucleotide polymorphisms (SNPs) in the interleukin-18 ( IL18 ) gene (rs187238, g.-137G > C; rs1946518, g.-607C > A) and one SNP of the IL12B gene (rs3212227 g.*159A > C, 3'UTR) with the age of onset for type 1 diabetes mellitus (DM1). A total of 1,101 patients with DM1 enrolled in 13 centers from different regions of Brazil were genotyped with TaqMan assay and classified according to the ancestry. Our results show that an SNP in IL18 gene could be associated with DM1 age onset, taking into account that this studied variation affects gene expression.

Association between Toll-like receptors (TLR) and NOD-like receptor (NLR) polymorphisms and lipid and glucose metabolism.

Recent evidences had shown activation of TLR (toll-like receptors) and NLR (nod-like receptors) in response to imbalance in nutrients intake, such as lipid and glucose. The main aim of this study was to investigate possible associations between 11 SNPs in TLR2, TLR4, NLRC4, CARD8 and NEK7 genes and lipid and glucose metabolism. Sample was composed by healthy children and adolescents (n = 158) and adults (n = 115). DNA extraction was obtained by salting-out and sample genotyping by matrix-assisted laser desorption ionization time-of-flight mass spectrometry based system. LDL-cholesterol, HDL-cholesterol, triglycerides, total cholesterol, glucose and insulin were measured by standard automated methods. Means were compared by t-test or Mann-Whitney test. Univariate and multivariate logistic regression were used to verify association between polymorphisms and lipid and glucose markers. Seven polymorphisms in 5 genes were associated with lipid and glucose parameters. For lipid parameters, the following associations were found: higher LDL-C levels and C allele of rs1554973 (TLR4) and G allele of rs6671879 (NEK7); higher HDL-cholesterol levels and A allele of rs13105517 (TLR2); higher total cholesterol and TT genotype of rs3804099 (TLR2) and G allele of rs6671879 (NEK7); higher triglycerides levels and G allele of rs455060 (NLRC4). For glucose parameters associations were found between C allele of rs7258674 (CARD8) and higher glucose levels, and between C allele of rs212704 (NLRC4) and G allele of rs455060 (NLRC4) and insulin levels. These findings indicate a relationship between polymorphisms of TLRs and NLRs genes and markers of lipid and glucose metabolism.

FTO rs9939609 A allele influences anthropometric outcome in response to dietary intervention, but not in response to physical exercise program.

PURPOSE: The fat mass and obesity-associated (FTO) gene is involved in energy homeostasis. The A allele of the rs9939609 (SNP; T>A) is associated with obesity and higher food intake, while its effect in energy expenditure remains unclear. The aim of this study is to examine whether FTO rs9939609 is associated with the anthropometric outcomes of a physical exercise program and a dietary intervention. METHODS: We studied two independent samples. The first was composed by children and adolescents in which overweight and obese individuals were submitted to a physical exercise program (n = 136) and normal weight participants served as a control group (n = 172). The second sample was composed by obese women submitted to a hypocaloric dietary intervention (n = 126). RESULTS: Physical exercise and dietary intervention were effective, independently of genotype. We found no association of FTO rs9939609 with obesity in children and adolescents (p = 0.67). The rs9939609 affected the response to dietary intervention in obese women: A allele carriers reduced 2.7 cm less of abdominal circumference (AC) than homozygous TT (p = 0.04), while no effect was observed in response to physical exercise in overweight and obese children and adolescents. CONCLUSIONS: The A allele is associated with a worse outcome in response to the hypocaloric dietary intervention regarding abdominal circumference reduction; the same allele did not show interaction with any anthropometric outcomes in response to the exercise program applied.

Effects of polymorphisms in APOB, APOE, HSD11ß1, PLIN4, and ADIPOQ genes on lipid profile and anthropometric variables related to obesity in children and adolescents.

Genes can influence lipid profile and anthropometric variables related to obesity. The present study aimed to verify if variants of the APOE, APOB, ADIPOQ, HSD11ß1, and PLIN4 genes are associated with lipid levels or anthropometric variables in a sample comprised of 393 Euro-Brazilian children and adolescents. DNA was genotyped by TaqMan allelic discrimination assay. The ε4 and ε2 alleles of the APOE gene were associated respectively with lower high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels (p=0.015 and p=0.012, respectively), while the ε3 allele was associated with higher abdominal circumference (p=0.0416) and excess weight (p=0.0001). The G allele (rs846910) of the HSD11ß1 gene was also associated with excess weight (p=0.039). No other association was found. Our results indicate that the ε4 and ε2 alleles could contribute to lower HDL-C and LDL-C levels, respectively, furthermore, the ε3 allele and the G allele (rs846910) of HSD11ß1 gene may be risk factors for excess of weight.These findings are very important because we observed that some genetic variants influence the lipid profile and anthropometric variables early in life.

FTO rs9939609 Does Not Interact with Physical Exercise but Influences Basal Insulin Metabolism in Brazilian Overweight and Obese Adolescents.

Purpose: The rs9939609 SNP (T > A) in FTO gene is associated with obesity and type 2 diabetes. The present study aimed at verifying whether this SNP influenced biochemical outcomes of children and adolescents who are overweight/obese submitted to a program of physical exercise and also if there was influence on basal levels of these biochemical variables. Methods: The sample was composed by 432 children and adolescents grouped in three ways (obese, overweight, and normal weight); of these, 135 children and adoloescents who are obese and overweight were submitted to a physical exercise program for 12 weeks. All were genotyped by TaqMan SNP genotyping assay. Results: The children and adolescents who are overweight/obese and carriers of AA genotype had higher levels of insulin (p=0.03) and HOMA (p=0.007) and lower levels of glucose (p=0.003), but the SNP did not modulate the response to physical exercise. Conclusions: In our study, the rs9939609 AA genotype was associated with parameters related to insulin metabolism but did not interact with physical exercise.

12-Week aerobic exercise and nutritional program minimized the presence of the 64Arg allele on insulin resistance.

BACKGROUND: The objective of the study was to investigate the response of 64Arg allele carriers of the ADRB3 gene (Trp64Arg polymorphism) in the anthropometric, cardiorespiratory and metabolic variables in overweight adolescents after a 12-week aerobic exercise and nutritional program. METHODS: A total of 92 overweight adolescents, 10-16 years old and of both genders, participated. Body composition, waist circumference (WC), pubertal stage status, blood pressure, glucose, insulin and lipid profile and direct maximal oxygen uptake were assessed at baseline and after 12 weeks of a training program. The homeostasis metabolic assessments [homeostasis model assessment of insulin resistance (HOMA-IR)] and quantitative insulin sensitivity check index (QUICKI) were determined and the Trp64Arg polymorphism of the ADRB3 gene was investigated by Taqman single nucleotide polymorphism (SNP) genotyping assays. Exercise sessions consisted of 100-min aerobic exercise and 20-min stretching, 3 times a week, totalizing 36 sessions. Multivariate analysis of variance (MANOVA), analysis of covariance (ANCOVA) and effect size were used for variables, with p<0.05 considered significant. RESULTS: In baseline, HOMA-IR was higher in carriers of the 64Arg allele and decreased more after 12 weeks than in non-carriers (p=0.01). The anthropometric, physical fitness and metabolic profiles had similar responses after training in carriers and non-carriers. CONCLUSIONS: Overweight adolescents present changes in body composition and physical fitness, independent of Trp64Arg genotypes. However, a 12-week aerobic exercise and nutritional program promoted greater reductions in insulin resistance in carriers of the 64Arg allele.

Effects of energetic restriction diet on butyrylcholinesterase in obese women from southern Brazil - A longitudinal study

Objective Butyrylcholinesterase (BChE) activity has been associated with obesity, lipid concentrations, and CHE2 locus phenotypes. This, the aim of this study was to evaluate the effects of an energetic restriction diet intervention on anthropometrical and biochemical variables and on absolute and relative BChE activity in CHE2 C5+ and CHE2 C5- individuals. Subjects and methods One hundred eleven premenopausal obese women from Southern Brazil participated in an energetic restriction diet intervention (deficit of 2500 kJ/day) for 8 weeks. Their anthropometric and biochemical parameters were evaluated before and after the intervention. Plasma BChE activity was measured, and BChE bands in plasma and CHE2 locus phenotypes were detected by electrophoresis. Results The dietetic intervention decreased anthropometric and biochemical parameters as well as absolute BChE activity and relative activity of the G4 band. The CHE2 C5+ phenotype presented a different effect when compared with the CHE2 C5- phenotype. The CHE2 C5+ phenotype showed an effect in absolute BChE activity and in the relative activity of the G4 form, maintaining higher BChE activity regardless of the metabolic changes. Conclusion In our study, 8 weeks was not sufficient time to lower the body mass index to normal, but it was enough to significantly reduce the absolute BChE activity, which became similar to the levels in nonobese individuals. CHE2 C5+ individuals were resistant to the decrease in BChE activity compared to CHE2 C5- individuals. This shows that the diet did not affect the CHE2 and G4 fraction complex and that the products of the CHE2 locus in association with BChE have a role in energy metabolism, maintaining high levels of enzymatic activity even after dietary intervention.

Effects of energetic restriction diet on butyrylcholinesterase in obese women from southern Brazil - A longitudinal study.

OBJECTIVE: Butyrylcholinesterase (BChE) activity has been associated with obesity, lipid concentrations, and CHE2 locus phenotypes. This, the aim of this study was to evaluate the effects of an energetic restriction diet intervention on anthropometrical and biochemical variables and on absolute and relative BChE activity in CHE2 C5+ and CHE2 C5- individuals. SUBJECTS AND METHODS: One hundred eleven premenopausal obese women from Southern Brazil participated in an energetic restriction diet intervention (deficit of 2500 kJ/day) for 8 weeks. Their anthropometric and biochemical parameters were evaluated before and after the intervention. Plasma BChE activity was measured, and BChE bands in plasma and CHE2 locus phenotypes were detected by electrophoresis. RESULTS: The dietetic intervention decreased anthropometric and biochemical parameters as well as absolute BChE activity and relative activity of the G4 band. The CHE2 C5+ phenotype presented a different effect when compared with the CHE2 C5- phenotype. The CHE2 C5+ phenotype showed an effect in absolute BChE activity and in the relative activity of the G4 form, maintaining higher BChE activity regardless of the metabolic changes. CONCLUSION: In our study, 8 weeks was not sufficient time to lower the body mass index to normal, but it was enough to significantly reduce the absolute BChE activity, which became similar to the levels in nonobese individuals. CHE2 C5+ individuals were resistant to the decrease in BChE activity compared to CHE2 C5- individuals. This shows that the diet did not affect the CHE2 and G4 fraction complex and that the products of the CHE2 locus in association with BChE have a role in energy metabolism, maintaining high levels of enzymatic activity even after dietary intervention.

Effect of BCHE single nucleotide polymorphisms on lipid metabolism markers in women

Abstract Butyrylcholinesterase (BChE) activity and polymorphisms in its encoding gene had previously been associated with metabolic traits of obesity. This study investigated the association of three single nucleotide polymorphisms (SNPs) in the BCHE gene: -116G > A (rs1126680), 1615GA (rs1803274), 1914A < G (rs3495), with obesity and lipid metabolism markers, body mass index (BMI), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG) levels, and BChE enzymatic activity in obese (BMI≥30/n = 226) and non-obese women (BMI < 25/n = 81). BCHE SNPs genotyping was obtained by TaqMan allelic discrimination assay and by RFLP-PCR. Plasmatic BChE activity was measured using propionylthiocholine as substrate. Similar allele frequencies were found in obese and non-obese women for the three studied SNPs (p > 0.05). The dominant and recessive models were tested, and different effects were found. The -116A allele showed a dominant effect in BChE activity reduction in both non-obese and obese women (p = 0.045 and p < 0.001, respectively). The 1914A > G and 1615GA SNPs influenced the TG levels only in obese women. The 1914G and the 1615A alleles were associated with decreased plasma levels of TG. Thus, our results suggest that the obesity condition, characterized by loss of energy homeostasis, is modulated by BCHE polymorphisms.

Effect of BCHE single nucleotide polymorphisms on lipid metabolism markers in women.

Butyrylcholinesterase (BChE) activity and polymorphisms in its encoding gene had previously been associated with metabolic traits of obesity. This study investigated the association of three single nucleotide polymorphisms (SNPs) in the BCHE gene: -116G > A (rs1126680), 1615GA (rs1803274), 1914A < G (rs3495), with obesity and lipid metabolism markers, body mass index (BMI), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG) levels, and BChE enzymatic activity in obese (BMI≥30/n = 226) and non-obese women (BMI < 25/n = 81). BCHE SNPs genotyping was obtained by TaqMan allelic discrimination assay and by RFLP-PCR. Plasmatic BChE activity was measured using propionylthiocholine as substrate. Similar allele frequencies were found in obese and non-obese women for the three studied SNPs (p > 0.05). The dominant and recessive models were tested, and different effects were found. The -116A allele showed a dominant effect in BChE activity reduction in both non-obese and obese women (p = 0.045 and p < 0.001, respectively). The 1914A > G and 1615GA SNPs influenced the TG levels only in obese women. The 1914G and the 1615A alleles were associated with decreased plasma levels of TG. Thus, our results suggest that the obesity condition, characterized by loss of energy homeostasis, is modulated by BCHE polymorphisms.

ADRB2 Gln27Glu polymorphism influenced changes in leptin but not body composition or metabolic and other inflammatory parameters after twelve weeks of combined training in overweight adolescents

ABSTRACT Aim To compare the anthropometric, metabolic, and inflammatory parameters of overweight adolescents after 12-weeks of resistance and aerobic training (CT), taking into account the Gln27Glu polymorphism of the β2 adrenergic receptor (ADRB2) gene. Methods Forty-seven adolescents (15.05±1.07y) were assigned to one of four groups, according to the presence or absence of the Glu27 allele: CT (CarrierT n=11; NoncarrierT n=11) or control (CarrierC n=13; NoncarrierC n=12). Body composition, abdominal fat, maturation, fitness, metabolic and lipid profile, inflammatory markers were assessed. The CT consisted of six resistance exercises, followed by 30 min of walking/running at 50-80% VO2max, totaling 60 min/session, three times a week. A mixed-model factorial ANOVA was used to compare variables at baseline and after 12-weeks. Results TC was effective in reducing total fat mass (NoncarrierT ES=.45, CarrierT ES=.27) and subcutaneous abdominal fat (NoncarrierT ES=.48, CarrierT ES=.46) and increasing lean mass (NoncarrierT ES=.58, CarrierT ES=.60) and fitness. CarrierT group showed a reduction in leptin (ES=.49). Conclusion The responses of body composition and physical fitness to TC were not influenced by the presence of the Gln27Glu polymorphism. However, only the Glu27 allele carriers showed reductions in leptin after 12-weeks. Besides, a lack of intervention caused obesogenic effects, especially in Glu27carriers.

Association between RAPH1 Gene Haplotypes and CHE2 Locus Phenotypes.

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.

Influence of polymorphisms of the beta-2 adrenergic receptor on the presence of exercise-induced bronchospasm in adolescents / Influência dos polimorfismos no receptor beta 2 adrenérgico na presença de broncoespasmo induzido pelo exercício em adolescentes

To determine the influence of polymorphisms of the beta-2 adrenergic receptor (ADRB2) in triggering exercise-induced bronchospasm (EIB) in adolescents. Methods: The subjects were divided into two groups: present EIB (EIB+) (n=45) and absent EIB (EIB−) (n=115). The bronchial provocation test with exercise was performed with a protocol that consisted of walking/running for at least eight minutes at high intensity, i.e., >85% of maximum heart rate, considering EIB+ as a 10% decrease in forced expiratory volume in one second (FEV1). The genotyping of the ADRB2 gene was performed by the Taqman method, using the Step One Plus system. Independent t-test, Mann–Whitney and Chi-square tests, as well as Spearman's correlation coefficient were used for the statistical analysis. Results: Age, body weight, height, FEV1, FVC and FEV1/FVC ratio were lower in the EIB+ group when compared to EIB− (p<0.05). There were no significant differences in the proportion of the allele at position 27 and Arg16Gly and Gln27Glu genotypes between the EIB+ and EIB− groups (p=0.26; p=0.97 and p=0.43, respectively). However, there was a trend toward statistical significance regarding the greater proportion of the Gly16 allele for the EIB+ when compared to the EIB− group (p=0.08). Conclusions: The presence of polymorphisms associated with the Glu27 allele and Arg16Gly and Gln27Glu genotypes had no influence on EIB. However, the statistical trend toward greater frequency of the Gly16 allele in individuals with EIB+ can be considered evidence of the influence of polymorphisms of the ADBR2 gene on EIB in adolescents.

Determinar a influência dos polimorfismos dos receptores adrenérgicos beta 2 (ADRB2) no desencadeamento de broncoespasmo induzido pelo exercício (BIE) em adolescentes. Métodos: Os sujeitos foram divididos em dois grupos: BIE presente (BIE+) (n=45) e BIE ausente (BIE−) (n=115). O teste de broncoprovocação com exercício foi feito com protocolo que consistiu em caminhar/correr durante no mínimo oito minutos em intensidade superior a 85% da frequência cardíaca máxima, considerando como BIE presente uma queda de 10% do volume expiratório forçado no primeiro segundo (VEF1). A genotipagem do gene ADRB2 foi feita pelo método Taqman por meio do aparelho Step One Plus. Para análise estatística usaram-se os testes t independente, U de Mann-Whitney, qui-quadrado e coeficiente de correlação de Spearman. Resultados: Idade, massa corporal, estatura, VEF1, CVF e relação VEF1/CVF foram menores no grupo BIE+ em comparação com o BIE− (p<0,05). Não houve diferenças significativas na proporção do alelo na posição 27 e dos genótipos Arg16Gly e Gln27Glu entre os grupos BIE+ e BIE− (p=0,26; p=0,97 e p=0,43, respectivamente). Entretanto, verificou-se uma tendência à significância estatística na maior proporção do alelo Gly16 para o grupo BIE+ comparado com o BIE− (p=0,08). Conclusões: A presença de polimorfismos associados ao alelo Glu27 e os genótipos Arg16Gly e Gln27Glu não influenciam no BIE. Porém, a tendência estatística observada para uma maior frequência do alelo Gly16 nos indivíduos com a presença de BIE pode ser considerado indício da influência de polimorfismos no gene ADBR2 no BIE em adolescentes.