Association of BCHE gene SNP rs1803274 (K-variant) and rs3495 with obesity in Pakistani population group
Status Publisher Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
39875593
DOI
10.1038/s41366-025-01715-7
PII: 10.1038/s41366-025-01715-7
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Obesity plays a crucial role in the development of metabolic disorders including diabetes, coronary and renal diseases. There are several factors involved in the pathology of obesity, including chronic inflammation and exposure to environmental contaminants. Recently, the cholinergic co-hydrolyzing enzyme BChE has been associated with clinical conditions such as diabetes and obesity. This study aims to investigate the levels of BChE and inflammatory markers in the serum, as well as the association between two specific BCHE gene variants (rs1803274 and rs3495) and the risk of obesity in the Pakistani population. METHODS: The study recruited 350 people with obesity and 200 volunteers with no obesity. Proinflammatory cytokines (TNF-α, IL-6, and IL-1β) levels were quantified using ELISA kits, while the analysis of BCHE gene SNPs rs1803274 (K-variant) and rs3495 was conducted using the tetra-primer amplification refractory mutation-PCR (tetra-ARM-PCR) and PCR-restriction fragment length polymorphism (RFLP) methods, respectively. Additionally, clinico-pathological parameters HDL, LDL, BMI, Homa-IR, insulin, glucose, blood pressure was also assessed in subjects of current study. RESULTS: Results showed significantly higher levels of BChE, TNF-α, IL-1β, and IL-6 in the obesity group compared to the group without obesity. Furthermore, the obesity group exhibited higher blood pressure and LDL levels, as well as lower HDL levels when compared to group without obesity. Logistic regression analysis revealed a relationship between obesity and higher BChE activity, blood pressure, LDL, and lower HDL levels. The study also found a statistically significant association between the BCHE gene SNPs rs1803274 (K-variant) and rs3495 and the risk of obesity (OR = 2.01; CI = 1.21-3.33; p = 0.0063; OR = 1.80; CI = 1.09-2.96, respectively). CONCLUSIONS: In conclusion, the study suggests that BChE and inflammatory cytokines play a significant role in the development and pathogenesis of obesity and can also act as good diagnostic biomarkers for obesity and its related metabolic disorders.
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Phelps NH, Singleton RK, Zhou B, Heap RA, Mishra A, Bennett JE, et al. Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. The Lancet. 2024;403:1027–50.
Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6–10. PubMed DOI
Bray GA. Pathophysiology of obesity. American J Clin Nutr. 1992;55:488S–94S. DOI
Han Y, Ma Y, Liu Y, Zhao Z, Zhen S, Yang X, et al. Plasma cholinesterase is associated with Chinese adolescent overweight or obesity and metabolic syndrome prediction. Diabetes Metab Syndr Obes. 2019;14:685–702. DOI
Nicolaidis S. Environment and obesity. Metabolism. 2019;100:153942. DOI
Chen YC, Chen PC, Hsieh WS, Portnov BA, Chen YA. Yungling LL. Environmental factors associated with overweight and obesity in taiwanese children. Paediatr Perinat Epidemiol. 2012;26:561–71. PubMed DOI
Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet. 1997;27:325–51. PubMed DOI
Zaitlen N, Kraft P, Patterson N, Pasaniuc B, Bhatia G, Pollack S, et al. Using extended genealogy to estimate components of heritability for 23 quantitative and dichotomous traits. PLoS Genet. 2013;9:e1003520. PubMed DOI PMC
Goodarzi MO. Genetics of obesity: what genetic association studies have taught us about the biology of obesity and its complications. Lancet Diabetes Endocrinol. 2018;6:223–36. PubMed DOI
Nettore IC, Franchini F, Palatucci G, Macchia PE, Ungaro P. Epigenetic mechanisms of endocrine-disrupting chemicals in obesity. Biomedicines. 2021;9:1716. PubMed DOI PMC
Pezzementi L, Nachon F, Chatonnet A. Evolution of acetylcholinesterase and butyrylcholinesterase in the vertebrates: an atypical butyrylcholinesterase from the Medaka Oryzias latipes. PLoS One. 2011;6:e17396. PubMed DOI PMC
Darvesh S, Hopkins DA, Geula C. Neurobiology of butyrylcholinesterase. Nat Rev Neurosci. 2003;4:131–8. PubMed DOI
Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ. The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med. 2003;9:125–34. PubMed DOI PMC
Tracey KJ. Physiology and immunology of the cholinergic anti-inflammatory pathway. J Clin Invest. 2007;117:289–96. PubMed DOI PMC
Frouni I, Kwan C, Belliveau S, Huot P. Cognition, and serotonin in Parkinson’s disease. Prog Brain Res. 2022;269:373–403. PubMed DOI
Reale M, Costantini E. Cholinergic modulation of the immune system in neuroinflammatory diseases. Diseases. 2021;9:29. PubMed DOI PMC
Bono GF, Simão-Silva DP, Batistela MS, Josviak ND, Dias PF, Nascimento GA, et al. Butyrylcholinesterase: K variant, plasma activity, molecular forms and rivastigmine treatment in Alzheimer’s disease in a Southern Brazilian population. Neurochem Int. 2015;81:57–62. PubMed DOI
Babaoglu MO, Ocal T, Bayar B, Kayaalp SO, Bozkurt A. Frequency and enzyme activity of the butyrylcholinesterase K-variant in a Turkish population. Eur J Clin Pharmacol. 2004;59:875–7. PubMed DOI
Mbah Ntepe LJ, Habib R, Judith Laure N, Raza S, Nepovimova E. Kamil K, et. al. Oxidative Stress and Analysis of Selected SNPs of ACHE (rs 2571598), BCHE (rs 3495), CAT (rs 7943316), SIRT1 (rs 10823108), GSTP1 (rs 1695), and Gene GSTM1, GSTT1 in Chronic Organophosphates Exposed Groups from Cameroon and Pakistan. Int J Mol Sci. 2020;21:6432. PubMed DOI PMC
Bartels CF, Van der Spek AF, La Du BN. Two polymorphisms in the non-coding regions of the BCHE gene. Nucleic Acids Res. 1990;18:6171. PubMed DOI PMC
Furtado-Alle L, Tureck LV, de Oliveira CS, Hortega JV, Souza RL. Butyrylcholinesterase and lipid metabolism: Possible dual role in metabolic disorders. Chem Biol Interact. 2023;383:110680. PubMed DOI
Chaves TJ, Leite N, Milano GE, Milano GE, Souza RL, Chautard-Freire-Maia EA, et al. 116A and K BCHE gene variants associated with obesity and hypertriglyceridemia in adolescents from Southern Brazil. Chem Biol Interact. 2013;203:341–3. PubMed DOI
Ellman GL, Courtney KD, Andres JrV, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88–95. PubMed DOI
Worek F, Mast U, Kiderlen D, Diepold C, Eyer P. Improved determination of acetylcholinesterase activity in human whole blood. Clin Chim Acta. 1999;288:73–90. PubMed DOI
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9. PubMed DOI
Lahiri DK, Nurnberger JrJI. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 1991;19:5444. PubMed DOI PMC
Patočka J, Kuča K, Jun D. Acetylcholinesterase and butyrylcholinesterase–important enzymes of human body. Acta Medica. 2004;47:215–28. PubMed
Pohanka M. Butyrylcholinesterase as a biochemical marker. Bratisl Lek Listy. 2013;114:726–34. PubMed
Gazzi EN, Sorodoc V, Jaba IM, Lionte C, Bologa C, Lupusoru CE, et al. Profile of adult acute cholinesterase inhibitors substances poisoning–a 30-year analysis. Open Medicine. 2015;10:278–84.
Ogunkeye OO, Roluga AI. Serum cholinesterase activity helps to distinguish between liver disease and non-liver disease aberration in liver function tests. Pathophysiology. 2006;13:91–3. PubMed DOI
Hamouda AF, Khardali IA, Attafi IM, Oraiby ME, Attafi MA, Muyidi AM, et al. Study the Relation Between Acetylcholinesterase and Obesity in University Students. Int J of Nutr Food Sci. 2019;8:46–51. DOI
Rao AA, Reddy CS, Sridhar GR, Annapurna A, Hanuman T, Prameela M, et al. Enhanced butyrylcholinesterase activity may be the common link in triggering low-grade systemic inflammation and decrease in cognitive function in diabetes mellitus and Alzheimer’s disease. Curr Nutr Food Sci. 2008;4:213–6. DOI
Tangvarasittichai S, Pongthaisong S, Meemark S, Tangvarasittichai O. Abdominal obesity associated with elevated serum butyrylcholinesterase activity, insulin resistance and reduced high density lipoprotein-cholesterol levels. Indian J Clin Biochem. 2015;30:275–80. PubMed DOI
Boberg DR, Furtado-Alle L, Souza RL, Chautard-Freire-Maia EA. Molecular forms of butyrylcholinesterase and obesity. Genet Mol Biol. 2010;33:452–4. PubMed DOI PMC
De Vriese C, Gregoire F, Lema-Kisoka R, Waelbroeck M, Robberecht P, Delporte C. Ghrelin degradation by serum and tissue homogenates: identification of the cleavage sites. Endocrinology. 2004;145:4997–5005. PubMed DOI
Valle AM, Radić Z, Rana BK, Whitfield JB, O’Connor DT, Martin NG, et al. The cholinesterases: analysis by pharmacogenomics in man. Chem Biol Interact. 2008;175:343–5. PubMed DOI PMC
Ha ZY, Mathew S, Yeong KY. Butyrylcholinesterase: a multifaceted pharmacological target and tool. Curr Protein Pept Sci. 2020;21:99–109. PubMed DOI
Czura CJ, Friedman SG, Tracey KJ. Neural inhibition of inflammation: the cholinergic anti-inflammatory pathway. J Endotoxin Res. 2003;9:409–13. PubMed DOI
Frühbeck G. The adipose tissue as a source of vasoactive factors. Curr Med Chem Cardiovasc Hematol Agents. 2004;2:197–208. PubMed DOI
Caër C, Rouault C, Le Roy T, Poitou C, Aron-Wisnewsky J, Torcivia A, et al. Immune cell-derived cytokines contribute to obesity-related inflammation, fibrogenesis and metabolic deregulation in human adipose tissue. Sci Rep. 2017;7:3000. PubMed DOI PMC
Munir S, Habib R, Awan S, Bibi N, Tanveer A, Batool S, et al. Biochemical Analysis and Association of Butyrylcholinesterase SNPs rs3495 and rs1803274 with Substance Abuse Disorder. J Mol Neurosci. 2019;67:445–55. PubMed DOI
Lockridge O. Review of human butyrylcholinesterase structure, function, genetic variants, history of use in the clinic, and potential therapeutic uses. Pharmacol Ther. 2015;148:34–46. PubMed DOI
Shields KA, Lewis J. The Identification of Butyrylcholinesterase (BCHE) Polymorphisms in a Small Australian Defence Force Cohort. Human Protection and Performance Division, Defence Science and Technology Organisation; 2011.
Aeinehband S, Lindblom RP, Al Nimer F, Vijayaraghavan S, Sandholm K, Khademi M, et al. Complement component C3 and butyrylcholinesterase activity are associated with neurodegeneration and clinical disability in multiple sclerosis. PLoS One. 2015;10:e0122048. PubMed DOI PMC
Pleva L, Kovarova P, Faldynova L, Plevova P, Hilscherova S, Zapletalova J, et al. The rs1803274 polymorphism of the BCHE gene is associated with an increased risk of coronary in-stent restenosis. BMC Cardiovasc Disord. 2015;15:1–9. DOI
Habieb MS, Elhelbawy NG, Alhanafy AM, Elhelbawy MG, Alkelany AS, Wahb AM. Study of the potential association of the BCHE rs1803274 genetic polymorphism and serum level of its protein with breast cancer. Meta Gene. 2021;29:100913. DOI
Negrão AB, Pereira AC, Guindalini C, Santos HC, Messas GP, Laranjeira R, et al. Butyrylcholinesterase genetic variants: association with cocaine dependence and related phenotypes. PLoS One. 2013;8:e80505. PubMed DOI PMC
Oliveira JD, Tureck LV, Santos WD, Saliba LF, Schenknecht CS, Scaraboto D, et al. Effect of BCHE single nucleotide polymorphisms on lipid metabolism markers in women. Genet Mol Biol. 2017;40:408–14. PubMed DOI PMC
Lima JK, Leite N, Turek LV, Souza RL, da Silva Timossi L, Osiecki AC, et al. 1914G variant of BCHE gene associated with enzyme activity, obesity and triglyceride levels. Gene. 2013;532:24–6. PubMed DOI
Kálmán J, Juhász A, Rakonczay Z, Ábrahám G, Zana M, Boda K, et al. Increased serum butyrylcholinesterase activity in type IIb hyperlipidaemic patients. Life Sci. 2004;75:1195–204. PubMed DOI
Benyamin B, Middelberg RP, Lind PA, Valle AM, Gordon S, Nyholt DR, et al. GWAS of butyrylcholinesterase activity identifies four novel loci, independent effects within BCHE and secondary associations with metabolic risk factors. Hum Mol Genet. 2011;20:4504–14. PubMed DOI PMC
Askalsky P, Kalapatapu RK, Foltin RW, Comer SD. Butyrylcholinesterase levels and subjective effects of smoked cocaine in healthy cocaine users. Am J Drug Alcohol Abuse. 2015;41:161–5. PubMed DOI