{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:24:15Z","timestamp":1772252655777,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>ANGPTL3 is an important regulator of lipid metabolism. Its inhibition in people with hypercholesteremia reduces plasma lipid levels dramatically. Genome-wide association studies have associated ANGPTL3 variants with lipid traits. Irisin, an exercise-modulated protein, has been associated with lipid metabolism. Intracellular accumulation of lipids impairs insulin action and contributes to metabolic disorders. In this study, we evaluate the impact of ANGPTL3 variants on levels of irisin and markers associated with lipid metabolism and insulin resistance. ANGPTL3 rs1748197 and rs12130333 variants were genotyped in a cohort of 278 Arab individuals from Kuwait. Levels of irisin and other metabolic markers were measured by ELISA. Significance of association signals was assessed using Bonferroni-corrected p-values and empirical p-values. The study variants were significantly associated with low levels of c-peptide and irisin. Levels of c-peptide and irisin were mediated by interaction between carrier genotypes (GA + AA) at rs1748197 and measures of IL13 and TG, respectively. While levels of c-peptide and IL13 were directly correlated in individuals with the reference genotype, they were inversely correlated in individuals with the carrier genotype. Irisin correlated positively with TG and was strong in individuals with carrier genotypes. These observations illustrate ANGPTL3 as a potential link connecting lipid metabolism, insulin resistance and cardioprotection.<\/jats:p>","DOI":"10.3390\/genes12050755","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T12:19:57Z","timestamp":1621253997000},"page":"755","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ANGPTL3 Variants Associate with Lower Levels of Irisin and C-Peptide in a Cohort of Arab Individuals"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9727-8321","authenticated-orcid":false,"given":"Muath","family":"Alanbaei","sequence":"first","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Kuwait University, Safat 13110, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8357-1252","authenticated-orcid":false,"given":"Mohamed","family":"Abu-Farha","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"},{"name":"Special Services Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prashantha","family":"Hebbar","sequence":"additional","affiliation":[{"name":"Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motasem","family":"Melhem","sequence":"additional","affiliation":[{"name":"Special Services Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Betty S.","family":"Chandy","sequence":"additional","affiliation":[{"name":"Special Services Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emil","family":"Anoop","sequence":"additional","affiliation":[{"name":"Special Services Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preethi","family":"Cherian","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Al-Khairi","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fadi","family":"Alkayal","sequence":"additional","affiliation":[{"name":"Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5409-3829","authenticated-orcid":false,"given":"Fahd","family":"Al-Mulla","sequence":"additional","affiliation":[{"name":"Research Division, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jehad","family":"Abubaker","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thangavel Alphonse","family":"Thanaraj","sequence":"additional","affiliation":[{"name":"Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5159","DOI":"10.1210\/en.2003-0870","article-title":"Minireview: Weapons of lean body mass destruction: The role of ectopic lipids in the metabolic syndrome","volume":"144","author":"Unger","year":"2003","journal-title":"Endocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1152\/physrev.00024.2006","article-title":"Disordered lipid metabolism and the pathogenesis of insulin resistance","volume":"87","author":"Savage","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2919","DOI":"10.1002\/dmrr.2919","article-title":"Angptl8 (betatrophin) role in diabetes and metabolic diseases","volume":"33","author":"Abubaker","year":"2017","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12944-018-0659-y","article-title":"New insights into angplt3 in controlling lipoprotein metabolism and risk of cardiovascular diseases","volume":"17","author":"Su","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1056\/NEJMoa1701329","article-title":"Cardiovascular and metabolic effects of angptl3 antisense oligonucleotides","volume":"377","author":"Graham","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","article-title":"The nhgri-ebi gwas catalog of published genome-wide association studies, targeted arrays and summary statistics 2019","volume":"47","author":"Buniello","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1194\/jlr.M028829","article-title":"Interaction between snps in the rxra and near angptl3 gene region inhibits apob reduction after statin-fenofibric acid therapy in individuals with mixed dyslipidemia","volume":"53","author":"Ma","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1093\/hmg\/ddn188","article-title":"Polygenic determinants of severe hypertriglyceridemia","volume":"17","author":"Wang","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s12017-011-8149-7","article-title":"Triglyceride level-influencing functional variants of the angptl3, cilp2, and trib1 loci in ischemic stroke","volume":"13","author":"Jaromi","year":"2011","journal-title":"Neuromol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"E1266","DOI":"10.1210\/jc.2012-1298","article-title":"Mutations in the angptl3 gene and familial combined hypolipidemia: A clinical and biochemical characterization","volume":"97","author":"Minicocci","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4788","DOI":"10.1038\/s41467-019-12703-7","article-title":"A comprehensive study of metabolite genetics reveals strong pleiotropy and heterogeneity across time and context","volume":"10","author":"Gallois","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/S0140-6736(14)61217-4","article-title":"Hdl and cardiovascular disease","volume":"384","author":"Rader","year":"2014","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1001\/jama.2009.1619","article-title":"Major lipids, apolipoproteins, and risk of vascular disease","volume":"302","author":"Sarwar","year":"2009","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.jacc.2017.12.006","article-title":"Lipids, lipoproteins, and metabolites and risk of myocardial infarction and stroke","volume":"71","author":"Holmes","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Girona, J., Amigo, N., Ibarretxe, D., Plana, N., Rodriguez-Borjabad, C., Heras, M., Ferre, R., Gil, M., Correig, X., and Masana, L. (2019). Hdl triglycerides: A new marker of metabolic and cardiovascular risk. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133151"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/nature09270","article-title":"Biological, clinical and population relevance of 95 loci for blood lipids","volume":"466","author":"Teslovich","year":"2010","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.atherosclerosis.2015.12.009","article-title":"Post-gwas methodologies for localisation of functional non-coding variants: Angptl3","volume":"246","author":"Oldoni","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa2004215","article-title":"Evinacumab for homozygous familial hypercholesterolemia","volume":"383","author":"Raal","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_19","first-page":"e1082","article-title":"2018 aha\/acc\/aacvpr\/aapa\/abc\/acpm\/ada\/ags\/apha\/aspc\/nla\/pcna guideline on the management of blood cholesterol: A report of the american college of cardiology\/american heart association task force on clinical practice guidelines","volume":"139","author":"Grundy","year":"2019","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"AlKhairi, I., Cherian, P., Abu-Farha, M., Madhoun, A.A., Nizam, R., Melhem, M., Jamal, M., Al-Sabah, S., Ali, H., and Tuomilehto, J. (2019). Increased expression of meteorin-like hormone in type 2 diabetes and obesity and its association with irisin. Cells, 8.","DOI":"10.3390\/cells8101283"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nrendo.2016.221","article-title":"Physiology and role of irisin in glucose homeostasis","volume":"13","author":"Perakakis","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"524","DOI":"10.3389\/fendo.2019.00524","article-title":"Irisin: A hope in understanding and managing obesity and metabolic syndrome","volume":"10","author":"Arhire","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.peptides.2018.03.018","article-title":"An update on the role of irisin in the regulation of endocrine and metabolic functions","volume":"104","author":"Mahgoub","year":"2018","journal-title":"Peptides"},{"key":"ref_24","first-page":"4708287","article-title":"The effects of exercise regimens on irisin levels in obese rats model: Comparing high-intensity intermittent with continuous moderate-intensity training","volume":"2018","author":"Rabia","year":"2018","journal-title":"BioMed Res. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","article-title":"A pgc1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis","volume":"481","author":"Bostrom","year":"2012","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.cmet.2012.02.010","article-title":"Irisin, turning up the heat","volume":"15","author":"Villarroya","year":"2012","journal-title":"Cell Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"E9","DOI":"10.1038\/nature11364","article-title":"Is irisin a human exercise gene?","volume":"488","author":"Timmons","year":"2012","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6561726","DOI":"10.1155\/2019\/6561726","article-title":"Exercise-induced irisin, the fat browning myokine, as a potential anticancer agent","volume":"2019","author":"Maalouf","year":"2019","journal-title":"J. Obes."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation plink: Rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/sj.hdy.6800717","article-title":"Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix","volume":"95","author":"Li","year":"2005","journal-title":"Heredity"},{"key":"ref_31","unstructured":"R Core Team (2020). R: A Language and Environment for Statistical Computing, R Core Team."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1038\/ng.3977","article-title":"Exome-wide association study of plasma lipids in >300,000 individuals","volume":"49","author":"Liu","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ng.75","article-title":"Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans","volume":"40","author":"Kathiresan","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"492","DOI":"10.18632\/aging.101407","article-title":"Strong impact of natural-selection-free heterogeneity in genetics of age-related phenotypes","volume":"10","author":"Kulminski","year":"2018","journal-title":"Aging"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/s41586-019-1310-4","article-title":"Genetic analyses of diverse populations improves discovery for complex traits","volume":"570","author":"Wojcik","year":"2019","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/ng.76","article-title":"Newly identified loci that influence lipid concentrations and risk of coronary artery disease","volume":"40","author":"Willer","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s00439-020-02222-7","article-title":"Genome-wide landscape establishes novel association signals for metabolic traits in the arab population","volume":"140","author":"Hebbar","year":"2020","journal-title":"Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.jacc.2020.05.070","article-title":"Targeting rna with antisense oligonucleotides and small interfering rna: Jacc state-of-the-art review","volume":"76","author":"Katzmann","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1056\/NEJMoa1002926","article-title":"Exome sequencing, angptl3 mutations, and familial combined hypolipidemia","volume":"363","author":"Musunuru","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"101067","DOI":"10.1016\/j.plipres.2020.101067","article-title":"The multi-faces of angptl8 in health and disease: Novel functions beyond lipoprotein lipase modulation","volume":"80","author":"Ghosh","year":"2020","journal-title":"Prog. Lipid Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1210\/me.2015-1292","article-title":"Irisin is regulated by car in liver and is a mediator of hepatic glucose and lipid metabolism","volume":"30","author":"Mo","year":"2016","journal-title":"Mol. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"150272","DOI":"10.1098\/rsob.150272","article-title":"The angptl3-4-8 model, a molecular mechanism for triglyceride trafficking","volume":"6","author":"Zhang","year":"2016","journal-title":"Open Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s12933-017-0627-2","article-title":"Plasma irisin is elevated in type 2 diabetes and is associated with increased e-selectin levels","volume":"16","author":"Rana","year":"2017","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4899","DOI":"10.1210\/jc.2013-2373","article-title":"Circulating irisin in relation to insulin resistance and the metabolic syndrome","volume":"98","author":"Park","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.jhep.2013.04.030","article-title":"Irisin is inversely associated with intrahepatic triglyceride contents in obese adults","volume":"59","author":"Zhang","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cca.2005.12.026","article-title":"Lipid and lipoprotein dysregulation in insulin resistant states","volume":"368","author":"Avramoglu","year":"2006","journal-title":"Clin. Chim. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.arcmed.2005.01.005","article-title":"Regulation of plasma triglycerides in insulin resistance and diabetes","volume":"36","author":"Ginsberg","year":"2005","journal-title":"Arch. Med. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1055\/s-0029-1212190","article-title":"New aspects on biological activity of c-peptide in iddm patients","volume":"106","author":"Forst","year":"1998","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1177\/1479164117710446","article-title":"C-peptide: A predictor of cardiovascular mortality in subjects with established atherosclerotic disease","volume":"14","author":"Cardellini","year":"2017","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1055\/s-0035-1565177","article-title":"Fasting c-peptide and related parameters characterizing insulin secretory capacity for correctly classifying diabetes type and for predicting insulin requirement in patients with type 2 diabetes","volume":"124","author":"Becht","year":"2016","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1177\/1479164114564900","article-title":"C-peptide as a risk factor of coronary artery disease in the general population","volume":"12","year":"2015","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"ref_52","first-page":"907","article-title":"Significance of plasma c-peptide in obese african american adolescents","volume":"103","author":"Williams","year":"2011","journal-title":"J. Natl. Med. Assoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/j.sjbs.2018.05.027","article-title":"Biomarker potential of c-peptide for screening of insulin resistance in diabetic and non-diabetic individuals","volume":"25","author":"Khan","year":"2018","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.diabet.2016.06.007","article-title":"Fasting serum c-peptide levels (>1.6 ng\/ml) can predict the presence of insulin resistance in Japanese patients with type 2 diabetes","volume":"43","author":"Yanai","year":"2017","journal-title":"Diabetes Metab."},{"key":"ref_55","first-page":"7209872","article-title":"Serum levels of interleukin-13 increase in subjects with insulin resistance but do not correlate with markers of low-grade systemic inflammation","volume":"2018","author":"Palomera","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1172\/JCI64941","article-title":"Direct control of hepatic glucose production by interleukin-13 in mice","volume":"123","author":"Stanya","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/nm.3094","article-title":"Il-13 controls blood sugar","volume":"19","year":"2013","journal-title":"Nature Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"16056","DOI":"10.1038\/boneres.2016.56","article-title":"Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism","volume":"5","author":"Zhang","year":"2017","journal-title":"Bone Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/j.metabol.2012.09.002","article-title":"Fndc5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and ii. Mrna expression and circulating concentrations in response to weight loss and exercise","volume":"61","author":"Huh","year":"2012","journal-title":"Metabolism"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.molmet.2020.01.016","article-title":"Irisin: Still chasing shadows","volume":"34","author":"Albrecht","year":"2020","journal-title":"Mol. Metab."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/5\/755\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:02:42Z","timestamp":1760162562000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/5\/755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":60,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["genes12050755"],"URL":"https:\/\/doi.org\/10.3390\/genes12050755","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202105.0258.v1","asserted-by":"object"}]},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,17]]}}}