title: Association of glucocorticoid receptor haplotypes with body composition and metabolic parameters in HIV-infected patients from the FRAM study.
abstract: BACKGROUND
  HIV infection has been associated with dyslipidemia, insulin resistance, and changes in body composition, including loss of subcutaneous fat and skeletal muscle, with relative sparing of upper trunk and visceral fat. Because of its resemblance to Cushing's syndrome, caused by glucocorticoid excess, we hypothesized that variations in the glucocorticoid receptor (GR) gene, associated with changes in sensitivity to glucocorticoids, may be associated with such abnormalities in HIV-infected patients.
  
  
  METHODS
  This was a cross-sectional genetic association study.
  
  
  METHODS
  GR polymorphisms were determined in HIV-infected participants from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). We created haplotypes in 754 participants and assessed the associations with fasting metabolic parameters and body composition by MRI.
  
  
  RESULTS
  After stratification for ethnicity, we found no consistent pattern of associations between the described GR haplotypes and body composition or metabolic parameters in HIV-infected patients. However, we found a new haplotype comprising the Tth111I polymorphism in African-Americans. Heterozygous carriers of this haplotype (n=24) had significantly higher levels of high-density lipoprotein cholesterol compared with age-matched and sex-matched noncarriers (n=96) (median 55 vs. 44 mg/dl, P=0.026) and a tendency toward lower glucose (-5 mg/dl) and triglyceride (-21 mg/dl) levels and lower visceral adipose tissue mass (-0.22 l). CD4 count as well as skeletal muscle mass were also lower in carriers of this haplotype (-154 cells/μl and -1.6 l, respectively).
  
  
  CONCLUSIONS
  Although our cohort included only a small number of carriers of the new Tth111I haplotype, these results are suggestive that this GR haplotype may be associated with a healthier metabolic profile in African-Americans with HIV infection.
authors.affiliation: aDepartment of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands bDepartment of Medicine, University of California and Veterans Affairs Medical Center, San Francisco, California cDepartment of Medicine, New York University Medical Center, New York, New York, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Manenschijn
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.forename: Jan W
authors.initials: JW
authors.lastname: Koper
authors.forename: Ann
authors.initials: A
authors.lastname: Danoff
authors.forename: Elisabeth F C
authors.initials: EF
authors.lastname: van Rossum
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D001823:Body Composition / Q000235:genetics*; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D005947:Glucose / Q000378:metabolism*; D015658:HIV Infections / Q000208:ethnology / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D014280:Triglycerides / Q000378:metabolism*; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D011965:Receptors, Glucocorticoid; D014280:Triglycerides; D005947:Glucose