Racial Disparities in Methylation of NRF1, FTO, and LEPR Gene in Childhood Obesity

Abstract

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.

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

“…TAB2 [131], CCR4 [112], LTF (lactotransferrin) [126], hsa-mir-146a-5p [613], hsa-mir-8485 [614], BRCA1 [615], NFKB1 [616], TEAD1 [617], TFAP2C [618], FOXO3 [619 and NRF1 [620] risk factors have been shown to increase susceptibility to cardiovascular diseases. Several studies have shown that TAB2 [131], LTF (lactotransferrin) [487], BRCA1 [621], NFKB1 [622], TEAD1 [623], FOXO3 [624] and NRF1 [625] can be involved in the disease progression of obesity ., Altered expression of CCR4 [280], LTF (lactotransferrin) [295], CDH1 [313], CFTR (CF transmembrane conductance regulator) [317], hsa-mir-146a-5p [626], hsa-mir-195-5p [627], hsa-mir-4739 [628], HNF4A [629], NFKB1 [630], NR2F1 [631], FOXO3 [632] and NRF1 [633] are observed in diabetes mellitus. CCR4 [407], hsa-mir-146a-5p [634] and NFKB1 [635] were associated with psychiatric disorders.…”

Association of the DNA Methylation of Obesity-Related Genes with the Dietary Nutrient Intake in Children

“…Detailed information of the study participants has been previously given in Patel et al [ 34 ]. Briefly, children aged 6 to 10 years were recruited from Lee and Macon counties, AL.…”

“…The multiplex PCR was carried out for the three genes NRF1 , FTO , and LEPR , for which two primers and one probe for each gene were designed. Detailed protocols for each step have been mentioned in previous published article [ 34 ].…”

“…However, there is a gap in the literature in understanding the relationship between dietary intake of children and obesity-related gene methylation considering the racial disparities. In our previous study [ 34 ], we found that children who were overweight/obese (OW/OB) had increased methylation of the NRF1 and FTO genes and decreased methylation of the LEPR gene when compared to normal weight (NW). Specifically, African American (AA) children had significantly higher methylation of LEPR compared to European American (EA) children.…”

Single-nucleus RNA-sequencing reveals NRF1/NFE2L1 as a key factor determining the thermogenesis and cellular heterogeneity and dynamics of brown adipose tissues in mice

“…The cap ‘n’ collar-basic leucine zipper protein (CNC-bZIP) nuclear factor erythroid 2-related factor 1 (NFE2L1, also known as NRF1) is a master regulator controlling the transcription of a suite of genes involved in proteasomal homeostasis, cell metabolism and numerous stress responses, antioxidant response in particular [ [8] , [9] , [10] , [11] ]. A single nucleotide polymorphism (SNP), rs3764400, in the 5′-flanking region of the human NFE2L1 gene, appears to be associated with obesity in humans [ [12] , [13] , [14] , [15] ]. In addition, an epigenome-wide association study identified human NFE2L1 as one of the genes nearest to the sentinel methylation markers of a locus linked to BMI and adverse outcomes of obesity [ 15 , 16 ].…”