Linked Life Data

10084600

Source:http://linkedlifedata.com/resource/pubmed/id/10084600

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-4-13
pubmed:abstractText
Idiopathic hirsutism may result from an increase in the androgen receptor (AR)-mediated sensitivity of the hair follicle. The AR gene is located on the X-chromosome and contains a highly polymorphic trinucleotide repeat (CAGn) in its first exon, whose length and methylation pattern affect both AR expression and function. We analyzed these CAG repeats in the genomic DNA from 16 nonhyperandrogenic hirsute patients (Ferriman score: 16 +/- 4.7, mean +/- SD) and 10 normal controls (Ferriman score: 3 +/- 1.4), who were similar in their hormonal profiles. We found no difference in the number of CAG repeats between hirsute patients and controls, and no correlation between number of repeats and the Ferriman score or hormonal values. However, after DNA digestion with methylation-sensitive HpaII and measurement of the optical density, we found a marked decrease in the hirsute group (P < 0.0001), which was greater than in the control group (P = 0.0003). In addition, in the hirsute patients, the shorter of the two alleles was preferentially less methylated (P = 0.007), suggesting skewing of X-chromosome inactivation in the patients but not in the controls. When the mean optical density of both alleles was correlated with the Ferriman score, we observed a significant negative correlation (P = 0.02, r = -0.45), which became stronger when the shorter alleles were analyzed separately (P = 0.01; r = 0.48). We conclude that nonhyperandrogenic hirsutism is associated with skewing of X-chromosome inactivation in peripheral blood lymphocytes. This leads to the longer of the two AR alleles being preferentially methylated, allowing for the shorter (and presumably, more functional) allele to be expressed on the active X-chromosome. Further studies need to be performed to investigate whether this phenomenon is present in androgen-sensitive tissues in these patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1091-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Androgen receptor-mediated hypersensitivity to androgens in women with nonhyperandrogenic hirsutism: skewing of X-chromosome inactivation.
pubmed:affiliation
Section of Pediatric Endocrinology, DEB, NICHD, NIH, Bethesda, Maryland 20892-1862, USA. votteroa@cc1.nichd.nih.gov
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't