Genetic Polymorphisms of Carnosine Synthase -1(ATPGD1) and Serum Carnosine Levels in Relation to Cardiovascular Diseases in Iraqi Type 2 Diabetics
DOI:
https://doi.org/10.31351/vol33iss2pp179-189Keywords:
Carnosine ,Carnosine synthase -1(ATPGD1),Carnosine synthase -1 gene polymorphism,T2DM.Abstract
Diabetes mellitus (DM) is a metabolic disorder specified by persistent hyperglycemia that occurs when β-cell insulin production became unable to control blood glucose with deterioration of response for insulin. The consequent development of DM complications with increased risk for many diseases caused by damaged variety of biological systems, including blood vessels, eyes, kidneys, heart, and nerves. Carnosine is a natural dipeptide (β-alanyl-L-histidine) expressed in both the central nervous system and periphery, it occurs in several tissues most notably in muscle where they represent an appreciable fraction of the total water-soluble nitrogen-containing compounds. Carnosine is synthesized by a cytosolic amino acid ligase, carnosine synthase-1 (CARNS1; also known as ATP-grasp domain–containing protein 1, ATPGD1; EC 6.3.2.11).Several biological and physiological functions have been attributed to carnosine, such as being an anti-inflammatory and antioxidant agent, antiglycating actions, and as a modulator of mitochondrial metabolism. Carnosine level in human serum is affected by several enzymes like carnosine synthase-1 (responsible of carnosine synthesis),thus any genetic polymorphisms in these enzymes could have an impact on enzymes levels and therefore serum carnosine level with consequent increased risk for many diseases.
This study was aimed to estimate the occurrence of Carnosine synthase -1 SNP (rs 1790733) on chromosom11 (intron –variant) in Iraqi type 2 diabetics with and without cardio vascular diseases and it’s correlation with serum levels of carnosine & carnosine synthase-1 and their association with CVD as T2DM complication.
To achieve this aim Enzyme Linked Immunosorbent Assay (ELISA) specific kits were used to estimate serum levels of carnosine & carnosine synthase-1. High resolution melt technique (HRM) was applied for detecting gene polymorphism of carnosine synthase-1 gene (ATPGD1).
The results showed that gene polymorphism of SNP (rs1790733) increased the chance of CVD in T2DM patients by 84.5% by its effect to decrease the mean of serum levels of carnosine by decreased carnosine synthase-1 level that may correlate to development of CVD in T2DM patients.
Received 22/5/2023
Accepted 26/7/2023
Published 27/6/2024
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Raheem MF, Ali SH, Shareef LG. Impact of serum levels of vitamin D on lipid profiles, glycemic indices, and insulin resistance in obese type 2 diabetes patients: An observational study. F1000Research. 2022 Sep 6;11(1002):1002.
Salih BH, Ali SH, Allehibi KI. Serum Aldosterone Levels in Patients With Diabetic Nephropathy in Relation to Vascular Calcification. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2019 Jun 11;28(1):53-63.
Khamis AS, Ali SH, Al-Lehibi KI. The correlation between serum total adiponectin and hemoglobin in type 2 diabetic patients without microalbuminuria. Age (years). Iraqi Journal of Pharmaceutical Sciences(P-ISSN 1683-3597 E-ISSN 2521-3512).2012;55(2.231):53-23.
Abdulrahman Z, Alatrakji MQ, Al-Maliky AA, Hussein KI, Hussain SA. Influence of Metformin Dose and Treatment Adherence on Glycemic Control, Adiposity, and Cardiovascular Risk Markers in Iraqi Patients with T2DM. Journal of the Faculty of Medicine Baghdad. 2022;64(4):218-26.
Yonus SS, AlKataan MA. Mitochondrial Copies Number and Some Renal Function Biomarkers in Type 2 Diabetes Mellitus on Metformin. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2022 Dec 23;31(2):33-8.
Incalza MA, D'Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascular pharmacology. 2018 Jan 1;100:1-9.
Banerjee, S., Mukherjee, B., Poddar, M. K., & Dunbar, G. L. Carnosine improves aging‐induced cognitive impairment and brain regional neurodegeneration in relation to the neuropathological alterations in the secondary structure of amyloid beta (Aβ). Journal of Neurochemistry.2021; 158(3), 710-723.
Menini S, Iacobini C, Fantauzzi CB, Pugliese G. L-carnosine and its derivatives as new therapeutic agents for the prevention and treatment of vascular complications of diabetes. Current medicinal chemistry. 2020 Apr 1;27(11):1744-63.
Kwiatkowski S, Kiersztan A, Drozak J. Biosynthesis of carnosine and related dipeptides in vertebrates. Current Protein and Peptide Science. 2018 Aug 1;19(8):771-89.
Albrecht T, Schilperoort M, Zhang S, Braun JD, Qiu J, Rodriguez A, Pastene DO, Krämer BK, Köppel H, Baelde H, de Heer E, Anna Altomare A, Regazzoni L, Denisi A, Aldini G, van den Born J, Yard BA, Hauske SJ Carnosine attenuates the development of both type 2 diabetes and diabetic nephropathy in BTBR ob/ob mice. Sci Rep. 2017; 7:44492.
Zhao J, Shi L, Zhang LR. Neuroprotective effect of carnosine against salsolinol induced Parkinson's disease. Experimental and therapeutic medicine. 2017 Jul 1;14(1):664-70.
Diniz FC, Hipkiss AR, Ferreira GC. The Potential Use of Carnosine in Diabetes and Other Afflictions Reported in Long COVID Patients. Front Neurosci. 2022;16:898735. Published 2022 Jun 22.
Huang Y, Wang J, Luo M, Yan D, Zhang C. Carnosine attenuates vascular smooth muscle cells calcification through mTOR signaling pathway. Aging Medicine. 2020 Sep;3(3):153-8.
Baye E, Ukropec J, De Courten MP, Vallova S, Krumpolec P, Kurdiova T, Aldini G, Ukropcova B, De Courten B. Effect of carnosine supplementation on the plasma lipidome in overweight and obese adults: a pilot randomised controlled trial. Scientific Reports. 2017 Dec 12;7(1):1-7.
Khudhur SS, Saleh ES, Alosami MH. The Impact of rs767455 and rs1061622 Polymorphisms on Treatment Outcomes in Iraqi Ankylosing Spondylitis Patients Taking Etanercept. The Egyptian Journal of Hospital Medicine. 2023 Jan 1;90(2):3488-94.
Schmöhl, F., Peters, V., Schmitt, C. P., Poschet, G., Büttner, M., Li, X. & Kroll, J. CNDP1 knockout in zebrafish alters the amino acid metabolism, restrains weight gain, but does not protect from diabetic complications. Cellular and Molecular Life Sciences, 2019:76(22), 4551-4568.
Caruso G, Fresta CG, Grasso M, Santangelo R, Lazzarino G, Lunte SM, Caraci F. Inflammation as the common biological link between depression and cardiovascular diseases: Can carnosine exert a protective role?. Current Medicinal Chemistry. 2020 Apr 1;27(11):1782-800.
Jameel MG, Alhakeem ZM, Al-Osami MH. Prevalence of AGER gene polymorphism in post menopause Iraqi sample with Osteoporosis and osteopenia in type 2DM. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2022 Dec 24;31(2):202-10.
Ali R, Baban R, Ali S. The association between PON1 gene polymorphisms (Q192R and L55M) and nephrotic syndrome in Iraqi children. Baghdad Journal of Biochemistry and Applied Biological Sciences. 2021 Jul 21;2(03):120-32.
Caruso G, Caraci F, Jolivet RB. Pivotal role of carnosine in the modulation of brain cells activity: Multimodal mechanism of action and therapeutic potential in neurodegenerative disorders. Progress in neurobiology. 2019 Apr 1;175:35-53.
Sureshkumar K, Durairaj M, Srinivasan K, Goh KW, Undela K, Mahalingam VT, Ardianto C, Ming LC, Ganesan RM. Effect of L-Carnosine in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis. Frontiers in Bioscience-Landmark. 2023 Jan 18;28(1):18.
Wang C, Yuan Y, Zheng M, Pan AN, Wang M, Zhao M, Li Y, Yao S, Chen S, Wu S, Xue H. Association of age of onset of hypertension with cardiovascular diseases and mortality. Journal of the American College of Cardiology. 2020 Jun 16;75(23):2921-30.
Kohl TO, Ascoli CA. Immunometric double-antibody sandwich enzyme-linked immunosorbent assay. Cold Spring Harb Protoc.2017;1(6):458–62.
Alan H. B. Wu. Immunochemical Techniques. In: Michael L.Bishop, Edward P. Fody LES, editor. Clinical Chemistry Principles, Techniques, and Correlations. 8th ed. Philadelphia:Wolters Kluwer; 2018. p. 437–80.
Technical Manual ReliaPrep™ Blood gDNA Miniprep System Instructions for Use of ProductsA5080, A5081 and A5082.
Wittwer CT, Reed GH, Gundry CN, Vandersteen JG, Pryor RJ. High-resolution genotyping by amplicon melting analysis using LCGreen. Clinical chemistry. 2003 Jun 1;49(6):853-60.
Ameen IA, Saleh E, Mhaibes SH, Taha K, Dawood DA, Kamil HS. Evaluation of some inflammatory cytokines and Glycated hemoglobin in uncontrolled type 2 diabetes mellitus with nephropathy. Indian Journal of Forensic Medicine & Toxicology. 2020 Apr 29;14(2):1628-32.
AL-Qadhi HI, AL-Kinani TA, Obeed AA. Effect of Dapagliflozin on hemoglobin level in heart failure patients with chronic kidney disease and/or diabetes. Journal of the Faculty of Medicine. 2022;4(64), Pages 203-207
Caruso G, Fresta CG, Grasso M, Santangelo R, Lazzarino G, Lunte SM, Caraci F. Inflammation as the common biological link between depression and cardiovascular diseases: Can carnosine exert a protective role?. Current Medicinal Chemistry. 2020 Apr 1;27(11):1782-800.
Huang Y, Wang J, Luo M, Yan D, Zhang C. Carnosine attenuates vascular smooth muscle cells calcification through mTOR signaling pathway. Aging Medicine. 2020 Sep;3(3):153-8.
Hauck AK, Huang Y, Hertzel AV, Bernlohr DA. Adipose oxidative stress and protein carbonylation. Journal of Biological Chemistry. 2019 Jan 25;294(4):1083-8.
Calabrese V, Scuto M, Salinaro AT, Dionisio G, Modafferi S, Ontario ML, Greco V, Sciuto S, Schmitt CP, Calabrese EJ, Peters V. Hydrogen sulfide and carnosine: modulation of oxidative stress and inflammation in kidney and brain axis. Antioxidants. 2020 Dec 18;9(12):1303.
de Courten B, Kurdiova T, de Courten MP, Belan V, Everaert I, Vician M, Teede H, Gasperikova D, Aldini G, Derave W, Ukropec J. Muscle carnosine is associated with cardiometabolic risk factors in humans. PloS one. 2015 Oct 6;10(10):e0138707.
Matthews JJ, Dolan E, Swinton PA, Santos L, Artioli GG, Turner MD, Elliott-Sale KJ, Sale C. Effect of carnosine or β-alanine supplementation on markers of glycemic control and insulin resistance in humans and animals: a systematic review and meta-analysis. Advances in nutrition. 2021 Nov;12(6):2216-31.
Zhao J, Conklin DJ, Guo Y, Zhang X, Obal D, Guo L, Jagatheesan G, Katragadda K, He L, Yin X, Prodhan MA. Cardiospecific overexpression of ATPGD1 (carnosine synthase) increases histidine dipeptide levels and prevents myocardial ischemia reperfusion injury. Journal of the American Heart Association. 2020 Jun 16;9(12):e015222.
Zhang S, Xu J, Cui D, Jiang S, Xu X, Zhang Y, Zhu D, Xia L, Yard B, Wu Y, Zhang Q. Genotype distribution of CNDP1 polymorphisms in the healthy Chinese Han population: association with HbA1c and fasting blood glucose. Journal of Diabetes Research. 2020 Jul 18;2020.
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