Expression Levels of Obesity-related Genes Are Associated with Weight Change in Kidney Transplant Recipients

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Apr 2

PMID 23544116

Citations 11

Authors

Ann Cashion

Ansley Stanfill

Fridtjof Thomas

Lijing Xu

Thomas Sutter

James Eason

Mang Ensell

Ramin Homayouni

Affiliations

Soon will be listed here.

Abstract

Background: The aim of this study was to investigate the association of gene expression profiles in subcutaneous adipose tissue with weight change in kidney transplant recipients and to gain insights into the underlying mechanisms of weight gain.

Methodology/principal Findings: A secondary data analysis was done on a subgroup (n = 26) of existing clinical and gene expression data from a larger prospective longitudinal study examining factors contributing to weight gain in transplant recipients. Measurements taken included adipose tissue gene expression profiles at time of transplant, baseline and six-month weight, and demographic data. Using multivariate linear regression analysis controlled for race and gender, expression levels of 1553 genes were significantly (p<0.05) associated with weight change. Functional analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes classifications identified metabolic pathways that were enriched in this dataset. Furthermore, GeneIndexer literature mining analysis identified a subset of genes that are highly associated with obesity in the literature and Ingenuity pathway analysis revealed several significant gene networks associated with metabolism and endocrine function. Polymorphisms in several of these genes have previously been linked to obesity.

Conclusions/significance: We have successfully identified a set of molecular pathways that taken together may provide insights into the mechanisms of weight gain in kidney transplant recipients. Future work will be done to determine how these pathways may contribute to weight gain.

Citing Articles

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References

Elster E, Leeser D, Morrissette C, Pepek J, Quiko A, Hale D . Obesity following kidney transplantation and steroid avoidance immunosuppression. Clin Transplant. 2008; 22(3):354-9. DOI: 10.1111/j.1399-0012.2008.00792.x. View

Rodriguez-Acebes S, Palacios N, Botella-Carretero J, Olea N, Crespo L, Peromingo R . Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: distinct expression of cell-cycle- and differentiation-related genes. BMC Med Genomics. 2010; 3:61. PMC: 3022546. DOI: 10.1186/1755-8794-3-61. View

Dahlman I, Arner P . Obesity and polymorphisms in genes regulating human adipose tissue. Int J Obes (Lond). 2007; 31(11):1629-41. DOI: 10.1038/sj.ijo.0803657. View

Speliotes E, Willer C, Berndt S, Monda K, Thorleifsson G, Jackson A . Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010; 42(11):937-48. PMC: 3014648. DOI: 10.1038/ng.686. View

Baum C . Weight gain and cardiovascular risk after organ transplantation. JPEN J Parenter Enteral Nutr. 2001; 25(3):114-9. DOI: 10.1177/0148607101025003114. View

Zhang B, Kirov S, Snoddy J . WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res. 2005; 33(Web Server issue):W741-8. PMC: 1160236. DOI: 10.1093/nar/gki475. View

Dolinkova M, Dostalova I, Lacinova Z, Michalsky D, Haluzikova D, Mraz M . The endocrine profile of subcutaneous and visceral adipose tissue of obese patients. Mol Cell Endocrinol. 2008; 291(1-2):63-70. DOI: 10.1016/j.mce.2008.05.001. View

van den Ham E, Kooman J, Christiaans M, Nieman F, van Hooff J . Weight changes after renal transplantation: a comparison between patients on 5-mg maintenance steroid therapy and those on steroid-free immunosuppressive therapy. Transpl Int. 2003; 16(5):300-6. DOI: 10.1007/s00147-002-0502-1. View

Patel M . The effect of dietary intervention on weight gains after renal transplantation. J Ren Nutr. 1998; 8(3):137-41. DOI: 10.1016/s1051-2276(98)90005-x. View

10.

Mehta R, Birerdinc A, Hossain N, Afendy A, Chandhoke V, Younossi Z . Validation of endogenous reference genes for qRT-PCR analysis of human visceral adipose samples. BMC Mol Biol. 2010; 11:39. PMC: 2886049. DOI: 10.1186/1471-2199-11-39. View

11.

Cawley N, Zhou J, Hill J, Abebe D, Romboz S, Yanik T . The carboxypeptidase E knockout mouse exhibits endocrinological and behavioral deficits. Endocrinology. 2004; 145(12):5807-19. DOI: 10.1210/en.2004-0847. View

12.

Kasiske B, Snyder J, Gilbertson D, Matas A . Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003; 3(2):178-85. DOI: 10.1034/j.1600-6143.2003.00010.x. View

13.

Homayouni R, Heinrich K, Wei L, Berry M . Gene clustering by latent semantic indexing of MEDLINE abstracts. Bioinformatics. 2004; 21(1):104-15. DOI: 10.1093/bioinformatics/bth464. View

14.

Korsic M, Gotovac K, Nikolac M, Dusek T, Skegro M, Muck-Seler D . Gene expression in visceral and subcutaneous adipose tissue in overweight women. Front Biosci (Elite Ed). 2012; 4(8):2734-44. DOI: 10.2741/e587. View

15.

Xu N, Nilsson-Ehle P, Ahren B . Correlation of apolipoprotein M with leptin and cholesterol in normal and obese subjects. J Nutr Biochem. 2004; 15(10):579-82. DOI: 10.1016/j.jnutbio.2004.03.001. View

16.

Klimcakova E, Roussel B, Marquez-Quinones A, Kovacova Z, Kovacikova M, Combes M . Worsening of obesity and metabolic status yields similar molecular adaptations in human subcutaneous and visceral adipose tissue: decreased metabolism and increased immune response. J Clin Endocrinol Metab. 2010; 96(1):E73-82. DOI: 10.1210/jc.2010-1575. View

17.

Ooi E, Watts G, Chan D, Nielsen L, Plomgaard P, Dahlback B . Association of apolipoprotein M with high-density lipoprotein kinetics in overweight-obese men. Atherosclerosis. 2009; 210(1):326-30. DOI: 10.1016/j.atherosclerosis.2009.11.024. View

18.

Cheung C, Tso A, Cheung B, Xu A, Ong K, Fong C . Obesity susceptibility genetic variants identified from recent genome-wide association studies: implications in a chinese population. J Clin Endocrinol Metab. 2010; 95(3):1395-403. DOI: 10.1210/jc.2009-1465. View

19.

Bauer F, Elbers C, Adan R, Loos R, Onland-Moret N, Grobbee D . Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference. Am J Clin Nutr. 2009; 90(4):951-9. DOI: 10.3945/ajcn.2009.27781. View

20.

Wardlaw S . Hypothalamic proopiomelanocortin processing and the regulation of energy balance. Eur J Pharmacol. 2011; 660(1):213-9. PMC: 3095770. DOI: 10.1016/j.ejphar.2010.10.107. View