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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. DESIGN:This was a cross-sectional genetic association study. MATERIALS AND 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). CONCLUSION: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.

journal_name

Pharmacogenet Genomics

journal_title

Pharmacogenetics and genomics

authors

Manenschijn L,Scherzer R,Koper JW,Danoff A,van Rossum EF,Grunfeld C

doi

10.1097/FPC.0000000000000029

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

156-61

issue

eissn

1744-6872

issn

1744-6880

journal_volume

pub_type

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Association of glucocorticoid receptor haplotypes with body composition and metabolic parameters in HIV-infected patients from the FRAM study.