Obesity Related Methylation Changes in DNA of Peripheral Blood Leukocytes

Overview

Journal BMC Med

Publisher Biomed Central

Specialty General Medicine

Date 2010 Dec 24

PMID 21176133

Citations 107

Authors

Xiaoling Wang

Haidong Zhu

Harold Snieder

Shaoyong Su

David Munn

Gregory Harshfield

Bernard L Maria

Yanbin Dong

Frank Treiber

Bernard Gutin

Huidong Shi

Affiliations

Soon will be listed here.

Abstract

Background: Despite evidence linking obesity to impaired immune function, little is known about the specific mechanisms. Because of emerging evidence that immune responses are epigenetically regulated, we hypothesized that DNA methylation changes are involved in obesity induced immune dysfunction and aimed to identify these changes.

Method: We conducted a genome wide methylation analysis on seven obese cases and seven lean controls aged 14 to 18 years from extreme ends of the obesity distribution and performed further validation of six CpG sites from six genes in 46 obese cases and 46 lean controls aged 14 to 30 years.

Results: In comparison with the lean controls, we observed one CpG site in the UBASH3A gene showing higher methylation levels and one CpG site in the TRIM3 gene showing lower methylation levels in the obese cases in both the genome wide step (P = 5 × 10(-6) and P = 2 × 10(-5) for the UBASH3A and the TRIM3 gene respectively) and the validation step (P = 0.008 and P = 0.001 for the UBASH3A and the TRIM3 gene respectively).

Conclusions: Our results provide evidence that obesity is associated with methylation changes in blood leukocyte DNA. Further studies are warranted to determine the causal direction of this relationship as well as whether such methylation changes can lead to immune dysfunction.

Citing Articles

Obesity prolongs the pro-inflammatory response and attenuates bone healing on titanium implants.

Avery D, Morandini L, Sheakley L, Alajmi A, Bergey L, Donahue H Acta Biomater. 2024; 192():473-486.

PMID: 39586347 PMC: 11735295. DOI: 10.1016/j.actbio.2024.11.040.

DNA Methylation Signatures in Paired Placenta and Umbilical Cord Samples: Relationship with Maternal Pregestational Body Mass Index and Offspring Metabolic Outcomes.

Gomez-Vilarrubla A, Mas-Pares B, Carreras-Badosa G, Bonmati-Santane A, Martinez-Calcerrada J, Niubo-Pallas M Biomedicines. 2024; 12(2).

PMID: 38397903 PMC: 10886657. DOI: 10.3390/biomedicines12020301.

Insights into the role of nucleotide methylation in metabolic-associated fatty liver disease.

Zhang N, Tian X, Yan T, Wang H, Zhang D, Lin C Front Immunol. 2023; 14:1148722.

PMID: 37020540 PMC: 10067741. DOI: 10.3389/fimmu.2023.1148722.

Improper preanalytical processes on peripheral blood compromise RNA quality and skew the transcriptional readouts of mRNA and LncRNA.

He Y, Dong L, Yi H, Zhang L, Shi X, Su L Front Genet. 2023; 13:1091685.

PMID: 36685907 PMC: 9845260. DOI: 10.3389/fgene.2022.1091685.

Drastic transformation of visceral adipose tissue and peripheral CD4 T cells in obesity.

Shirakawa K, Sano M Front Immunol. 2023; 13:1044737.

PMID: 36685567 PMC: 9846168. DOI: 10.3389/fimmu.2022.1044737.

References

Karalis K, Giannogonas P, Kodela E, Koutmani Y, Zoumakis M, Teli T . Mechanisms of obesity and related pathology: linking immune responses to metabolic stress. FEBS J. 2009; 276(20):5747-54. DOI: 10.1111/j.1742-4658.2009.07304.x. View

Wild S, Roglic G, Green A, Sicree R, King H . Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004; 27(5):1047-53. DOI: 10.2337/diacare.27.5.1047. View

Smale S . The establishment and maintenance of lymphocyte identity through gene silencing. Nat Immunol. 2003; 4(7):607-15. DOI: 10.1038/ni0703-607. View

Attwood J, Yung R, Richardson B . DNA methylation and the regulation of gene transcription. Cell Mol Life Sci. 2002; 59(2):241-57. PMC: 11146104. DOI: 10.1007/s00018-002-8420-z. View

Ge D, Dong Y, Wang X, Treiber F, Snieder H . The Georgia Cardiovascular Twin Study: influence of genetic predisposition and chronic stress on risk for cardiovascular disease and type 2 diabetes. Twin Res Hum Genet. 2007; 9(6):965-70. DOI: 10.1375/183242706779462877. View

Danaei G, Ding E, Mozaffarian D, Taylor B, Rehm J, Murray C . The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med. 2009; 6(4):e1000058. PMC: 2667673. DOI: 10.1371/journal.pmed.1000058. View

Tsygankov A . Multidomain STS/TULA proteins are novel cellular regulators. IUBMB Life. 2008; 60(4):224-31. DOI: 10.1002/iub.36. View

Martinez F, Gordon S, Locati M, Mantovani A . Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2006; 177(10):7303-11. DOI: 10.4049/jimmunol.177.10.7303. View

Collingwood T, Smirnova E, Bogush M, Carpino N, Annan R, Tsygankov A . T-cell ubiquitin ligand affects cell death through a functional interaction with apoptosis-inducing factor, a key factor of caspase-independent apoptosis. J Biol Chem. 2007; 282(42):30920-8. DOI: 10.1074/jbc.M706870200. View

10.

Wang X, Poole J, Treiber F, Harshfield G, Hanevold C, Snieder H . Ethnic and gender differences in ambulatory blood pressure trajectories: results from a 15-year longitudinal study in youth and young adults. Circulation. 2006; 114(25):2780-7. DOI: 10.1161/CIRCULATIONAHA.106.643940. View

11.

Anderson A, Caswell S . Obesity management--an opportunity for cancer prevention. Surgeon. 2009; 7(5):282-5. DOI: 10.1016/s1479-666x(09)80005-x. View

12.

Heinemeyer T, Wingender E, Reuter I, Hermjakob H, Kel A, Kel O . Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL. Nucleic Acids Res. 1998; 26(1):362-7. PMC: 147251. DOI: 10.1093/nar/26.1.362. View

13.

Mikhailik A, Ford B, Keller J, Chen Y, Nassar N, Carpino N . A phosphatase activity of Sts-1 contributes to the suppression of TCR signaling. Mol Cell. 2007; 27(3):486-97. PMC: 2709417. DOI: 10.1016/j.molcel.2007.06.015. View

14.

Gutin B, Johnson M, Humphries M, Hatfield-Laube J, Kapuku G, Allison J . Relationship of visceral adiposity to cardiovascular disease risk factors in black and white teens. Obesity (Silver Spring). 2007; 15(4):1029-35. DOI: 10.1038/oby.2007.602. View

15.

Sanna S, Jackson A, Nagaraja R, Willer C, Chen W, Bonnycastle L . Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Genet. 2008; 40(2):198-203. PMC: 2914680. DOI: 10.1038/ng.74. View

16.

Snieder H, Dong Y, Barbeau P, Harshfield G, Dalageogou C, Zhu H . Beta2-adrenergic receptor gene and resting hemodynamics in European and African American youth. Am J Hypertens. 2002; 15(11):973-9. DOI: 10.1016/s0895-7061(02)02991-6. View

17.

Al-Shahrour F, Diaz-Uriarte R, Dopazo J . FatiGO: a web tool for finding significant associations of Gene Ontology terms with groups of genes. Bioinformatics. 2004; 20(4):578-80. DOI: 10.1093/bioinformatics/btg455. View

18.

Li Y, Liu L, Tollefsbol T . Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. FASEB J. 2009; 24(5):1442-53. PMC: 2996891. DOI: 10.1096/fj.09-149328. View

19.

Zhu H, Chao J, Guo D, Li K, Huang Y, Hawkins K . Urinary prostasin: a possible biomarker for renal pressure natriuresis in black adolescents. Pediatr Res. 2009; 65(4):443-6. PMC: 3826778. DOI: 10.1203/PDR.0b013e3181994b85. View

20.

Rajsbaum R, Stoye J, OGarra A . Type I interferon-dependent and -independent expression of tripartite motif proteins in immune cells. Eur J Immunol. 2008; 38(3):619-30. DOI: 10.1002/eji.200737916. View