{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:49:38Z","timestamp":1789087778447,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alabama Agricultural Experiment Station","award":["1928770"],"award-info":[{"award-number":["1928770"]}]},{"name":"National Science Foundation EPSCoR RII Track-4 Research Fellowship","award":["1928770"],"award-info":[{"award-number":["1928770"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Childhood obesity has affected the health of millions of children around the world despite vigorous efforts by health experts. The obesity epidemic in the United States has disproportionately afflicted certain racial and ethnic minority groups. African American children are more likely than other children to have obesity-related risk factors such as hyperlipidemia, diabetes, cardiovascular disease, and coronavirus disease (COVID-19). For the reduction in obesity-related health inequalities to be successful, it is essential to identify the variables affecting various groups. A notable advancement in epigenetic biology has been made over the past decade. Epigenetic changes like DNA methylation impact on many genes associated with obesity. Here, we evaluated the DNA methylation levels of the genes NRF1, FTO, and LEPR from the saliva of children using real-time quantitative PCR-based multiplex MethyLight technology. ALU was used as a reference gene, and the Percent of Methylated Reference (PMR) was calculated for each sample. European American children showed a significant increase in PMR of NRF1 and FTO in overweight\/obese participants compared to normal weight, but not in African American children. After adjusting for maternal education and annual family income by regression analysis, the PMR of NRF1 and FTO was significantly associated with BMI z-score only in European American children. While for the gene LEPR, African American children had higher methylation in normal weight participants as compared to overweight\/obese and no methylation difference in European American children. The PMR of LEPR was significantly negative associated with the obesity measures only in African American children. These findings contribute to a race-specific link between NRF1, FTO, and LEPR gene methylation and childhood obesity.<\/jats:p>","DOI":"10.3390\/genes13112030","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T06:21:56Z","timestamp":1667542916000},"page":"2030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Racial Disparities in Methylation of NRF1, FTO, and LEPR Gene in Childhood Obesity"],"prefix":"10.3390","volume":"13","author":[{"given":"Priyadarshni","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaithinathan","family":"Selvaraju","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeganathan Ramesh","family":"Babu","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"},{"name":"Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, AL 36849, USA"},{"name":"Alabama Agricultural Experiment Station, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7594-5004","authenticated-orcid":false,"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Alabama Agricultural Experiment Station, Auburn University, Auburn, AL 36849, USA"},{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA"},{"name":"HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6358-0012","authenticated-orcid":false,"given":"Thangiah","family":"Geetha","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA"},{"name":"Boshell Metabolic Diseases and Diabetes Program, Auburn University, Auburn, AL 36849, USA"},{"name":"Alabama Agricultural Experiment Station, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"GBD 2015 Obesity Collaborators, Afshin, A., Forouzanfar, M.H., Reitsma, M.B., Sur, P., Estep, K., Lee, A., Marczak, L., Mokdad, A.H., and Moradi-Lakeh, M. (2017). Health effects of overweight and obesity in 195 countries over 25 years. N. Engl. J. Med., 377, 13\u201327.","DOI":"10.1056\/NEJMoa1614362"},{"key":"ref_2","unstructured":"Centers for Disease Control and Prevention (CDC) (2022, September 15). Prevalence of Childhood Obesity in the United States, Available online: https:\/\/www.cdc.gov\/obesity\/data\/childhood.html."},{"key":"ref_3","unstructured":"Foundation, R.W.J. (2022, September 15). State of Childhood Obesity-Alabama. Available online: https:\/\/stateofchildhoodobesity.org\/state-data\/?state=al."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1007\/s40615-020-00890-9","article-title":"Prevalence of Overweight and Obesity Among African American Children and Adolescents: Risk Factors, Health Outcomes, and Prevention\/Intervention Strategies","volume":"8","author":"Sutherland","year":"2021","journal-title":"J. Racial Ethn. Health Disparities"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1007\/s40615-020-00798-4","article-title":"Socioeconomic correlates of obesity in African-American and Caribbean-black men and women","volume":"8","author":"Barrington","year":"2021","journal-title":"J. Racial Ethn. Health Disparities"},{"key":"ref_6","first-page":"97","article-title":"Leisure time activities and obesity in school-aged inner city African American and Hispanic children","volume":"33","author":"Brandes","year":"2007","journal-title":"Pediatr. Nurs."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"809","DOI":"10.3945\/an.114.007070","article-title":"Food availability\/convenience and obesity","volume":"5","year":"2014","journal-title":"Adv. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ppedcard.2008.06.002","article-title":"Familial and environmental factors that contribute to pediatric overweight in African American populations: Implications for prevention and treatment","volume":"25","author":"Fitzgibbon","year":"2008","journal-title":"Prog. Pediatr. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/01.smj.0000253479.03665.6f","article-title":"Correlation between high risk obesity groups and low socioeconomic status in school children","volume":"100","author":"Vieweg","year":"2007","journal-title":"South. Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/nrendo.2013.57","article-title":"From obesity genetics to the future of personalized obesity therapy","volume":"9","author":"Froguel","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.2217\/14622416.9.12.1851","article-title":"Epigenetics and obesity","volume":"9","author":"Stoger","year":"2008","journal-title":"Pharmacogenomics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13148-015-0101-5","article-title":"Recent developments on the role of epigenetics in obesity and metabolic disease","volume":"7","author":"Tellam","year":"2015","journal-title":"Clin. Epigenetics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e01951","DOI":"10.1016\/j.heliyon.2019.e01951","article-title":"Mechanism of methylation and acetylation of high GDNF transcription in glioma cells: A review","volume":"5","author":"Zhang","year":"2019","journal-title":"Heliyon"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2217\/epi.11.22","article-title":"Epigenetics and lifestyle","volume":"3","author":"Baccarelli","year":"2011","journal-title":"Epigenomics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1042\/BST20211069","article-title":"Role of macronutrient intake in the epigenetics of obesity","volume":"50","author":"Patel","year":"2022","journal-title":"Biochem. Soc. Trans."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.3109\/07420528.2012.719967","article-title":"CLOCK, PER2 and BMAL1 DNA methylation: Association with obesity and metabolic syndrome characteristics and monounsaturated fat intake","volume":"29","author":"Milagro","year":"2012","journal-title":"Chronobiol. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nature08514","article-title":"Human DNA methylomes at base resolution show widespread epigenomic differences","volume":"462","author":"Lister","year":"2009","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nrg3354","article-title":"DNA methylation: Roles in mammalian development","volume":"14","author":"Smith","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tiffon, C. (2018). The Impact of Nutrition and Environmental Epigenetics on Human Health and Disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113425"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1476-511X-9-60","article-title":"Obesity induced by a pair-fed high fat sucrose diet: Methylation and expression pattern of genes related to energy homeostasis","volume":"9","author":"Lomba","year":"2010","journal-title":"Lipids Health Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rushing, A., Sommer, E.C., Zhao, S., Po\u2019e, E.K., and Barkin, S.L. (2020). Salivary epigenetic biomarkers as predictors of emerging childhood obesity. BMC Med. Genet., 21.","DOI":"10.1186\/s12881-020-0968-7"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1038\/s41598-019-38587-7","article-title":"Association between DNA methylation in obesity-related genes and body mass index percentile in adolescents","volume":"9","author":"He","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/nm.4481","article-title":"Brown adipose tissue thermogenic adaptation requires Nrf1-mediated proteasomal activity","volume":"24","author":"Bartelt","year":"2018","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.1073\/pnas.1032913100","article-title":"Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1","volume":"100","author":"Patti","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19676","DOI":"10.1074\/jbc.M602802200","article-title":"Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal transmembrane domain. Inhibition of nuclear translocation and transacting function","volume":"281","author":"Wang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_26","unstructured":"The Wellcome Trust Case Control Consortium (2007). Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 447, 661\u2013678."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1007\/s11892-014-0486-0","article-title":"FTO and obesity: Mechanisms of association","volume":"14","author":"Zhao","year":"2014","journal-title":"Curr. Diabetes Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/ng2048","article-title":"Variation in FTO contributes to childhood obesity and severe adult obesity","volume":"39","author":"Dina","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1126\/science.1151710","article-title":"The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase","volume":"318","author":"Gerken","year":"2007","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1172\/JCI45888","article-title":"Sixteen years and counting: An update on leptin in energy balance","volume":"121","author":"Gautron","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1634\/theoncologist.2010-0249","article-title":"DNA microarray analysis identifies CKS2 and LEPR as potential markers of meningioma recurrence","volume":"16","author":"Menghi","year":"2011","journal-title":"Oncologist"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e393","DOI":"10.1161\/CIR.0000000000000534","article-title":"Cardiovascular health in African Americans: A scientific statement from the American Heart Association","volume":"136","author":"Carnethon","year":"2017","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"660","DOI":"10.2471\/BLT.07.043497","article-title":"Development of a WHO growth reference for school-aged children and adolescents","volume":"85","author":"Onyango","year":"2007","journal-title":"Bull. World Health Organ."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/pr.2015.160","article-title":"LMS tables for waist-circumference and waist-height ratio Z-scores in children aged 5-19 y in NHANES III: Association with cardio-metabolic risks","volume":"78","author":"Sharma","year":"2015","journal-title":"Pediatr. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.3892\/ol.2017.5815","article-title":"Detection of SPG20 gene promoter-methylated DNA, as a novel epigenetic biomarker, in plasma for colorectal cancer diagnosis using the MethyLight method","volume":"13","author":"Rezvani","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Swiatowy, W.J., Drzewiecka, H., Kliber, M., Sasiadek, M., Karpinski, P., Plawski, A., and Jagodzinski, P.P. (2021). Physical activity and DNA Methylation in humans. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312989"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Oelsner, K.T., Guo, Y., To, S.B., Non, A.L., and Barkin, S.L. (2017). Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity. BMC Genom., 18.","DOI":"10.1186\/s12864-016-3473-9"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3389\/fendo.2018.00473","article-title":"Deciphering the roles of PPARgamma in adipocytes via dynamic change of transcription complex","volume":"9","author":"Ma","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Czogala, W., Czogala, M., Strojny, W., Wator, G., Wolkow, P., Wojcik, M., Bik Multanowski, M., Tomasik, P., Wedrychowicz, A., and Kowalczyk, W. (2021). Methylation and expression of FTO and PLAG1 genes in childhood obesity: Insight into anthropometric parameters and glucose-lipid metabolism. Nutrients, 13.","DOI":"10.3390\/nu13051683"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mizuno, T.M. (2018). Fat Mass and Obesity Associated (FTO) Gene and Hepatic Glucose and Lipid Metabolism. Nutrients, 10.","DOI":"10.20944\/preprints201810.0166.v1"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"154438","DOI":"10.1016\/j.metabol.2020.154438","article-title":"Identification of a novel leptin receptor (LEPR) variant and proof of functional relevance directing treatment decisions in patients with morbid obesity","volume":"116","author":"Voigtmann","year":"2021","journal-title":"Metabolism"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1159\/000511918","article-title":"Promoter methylation of LEP and LEPR before and after bariatric surgery: A cross-sectional study","volume":"14","author":"Wilhelm","year":"2021","journal-title":"Obes. Facts"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nature20784","article-title":"Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity","volume":"541","author":"Wahl","year":"2017","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Karnes, J.H., Arora, A., Feng, J., Steiner, H.E., Sulieman, L., Boerwinkle, E., Clark, C., Cicek, M., Cohn, E., and Gebo, K. (2021). Racial, ethnic, and gender differences in obesity and body fat distribution: An all of us research program demonstration project. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0255583"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1093\/abm\/kaaa063","article-title":"Interaction of neighborhood and genetic risk on waist circumference in African-American adults: A Longitudinal Study","volume":"55","author":"McDaniel","year":"2021","journal-title":"Ann. Behav. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1093\/abm\/kaz003","article-title":"Outcomes from a sequential multiple assignment randomized trial of weight loss strategies for African American adolescents with obesity","volume":"53","author":"Naar","year":"2019","journal-title":"Ann. Behav. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e27785","DOI":"10.1097\/MD.0000000000027785","article-title":"APOL1 renal risk variants are associated with obesity and body composition in African ancestry adults: An observational genotype-phenotype association study","volume":"100","author":"Nadkarni","year":"2021","journal-title":"Medicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1353\/hpu.2014.0038","article-title":"Race and socioeconomic differences in obesity and depression among Black and non-Hispanic White Americans","volume":"25","author":"Lincoln","year":"2014","journal-title":"J. Health Care Poor Underserved"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/978-1-61779-612-8_25","article-title":"Role of epigenetics in cancer health disparities","volume":"863","author":"Mohammed","year":"2012","journal-title":"Methods Mol. Biol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2030\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:10:35Z","timestamp":1760145035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,4]]},"references-count":49,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["genes13112030"],"URL":"https:\/\/doi.org\/10.3390\/genes13112030","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,4]]}}}