title: A Pilot Study of Demographic and Dopaminergic Genetic Contributions to Weight Change in Kidney Transplant Recipients.
abstract: Kidney transplant recipients often experience a significant amount of weight gain in the first year post-transplantation. While demographic factors such as age, race, and sex have been associated with weight gain in this population, these factors do not explain all of the variability seen. A number of studies have suggested that genetics also plays a critical role in weight changes. Recently, alterations in the activity of the neurotransmitter dopamine have been associated with weight change, and gene expression studies in kidney transplant recipients have supported this association. The purpose of this pilot study is to first examine the feasibility and methodology, and then to examine the associations of age, race, sex, and genotype for 13 SNPs and 3 VNTRs in 9 dopaminergic pathway genes (ANKK1, DRD2, DRD3, DRD4, SLC6A3/DAT1, MAOA, MAOB, COMT, CPE) for associations with percent weight change at 12 months post-transplantation. Seventy kidney transplant recipients had demographic and clinical data collected as a part of a larger observational study. DNA was extracted from repository buffy coat samples taken at the time of transplant, and genotyped using Taqman and PCR based methods. Three SNPs were independently associated with percent weight change: ANKK1 rs1800497 (r = -0.28, p = 0.05), SLC6A3/DAT1 rs6347 (p = 0.046), and CPE rs1946816 (p = 0.028). Stepwise regression modelling confirmed the combined associations of age (p = 0.0021), DRD4 VNTR 4/5 genotype (p = 0.0074), and SLC6A3/DAT1 rs6347 CC genotype (p = 0.0009) and TT genotype (p = 0.0004) with percent weight change in a smaller sample (n = 35) of these kidney transplant recipients that had complete genotyping. These associations indicate that there may be a genetic, and an age component to weight changes post transplantation.
authors.affiliation: Health Promotion and Development, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Ansley
authors.initials: A
authors.lastname: Stanfill
authors.affiliation: College of Nursing, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Donna
authors.initials: D
authors.lastname: Hathaway
authors.affiliation: National Institute of Nursing Research, National Insitutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Ann
authors.initials: A
authors.lastname: Cashion
authors.affiliation: Bioinformatics, University of Memphis, Memphis, Tennessee, United States of America.
authors.forename: Ramin
authors.initials: R
authors.lastname: Homayouni
authors.affiliation: College of Nursing, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cowan
authors.affiliation: College of Nursing, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Carol
authors.initials: C
authors.lastname: Thompson
authors.affiliation: Bioinformatics, University of Memphis, Memphis, Tennessee, United States of America.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Madahian
authors.affiliation: Health Promotion and Development, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Conley
mesh_terms: D000328:Adult; D000368:Aged; D043423:Carboxypeptidase H / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012307:Risk Factors; D066027:Transplant Recipients; D015430:Weight Gain / Q000235:genetics*; D055815:Young Adult
chemical_list: C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases; D043423:Carboxypeptidase H