Genetic basis of uterine fibroids uncovered

Oct 8 2012

By Helen Albert, Senior medwireNews Reporter

A mutation located near the fatty acid synthase gene (FASN) is associated with an increased predisposition for uterine leiomyomata or fibroids, suggest US study findings.

On further investigation, the team found that levels of the FAS protein were threefold higher in uterine tissue taken from women with fibroids than in normal uterine tissue, providing further evidence of a link between changes in FASN expression and uterine leiomyomata.

"Our discovery foretells a path to personalized medicine for women who have a genetic basis for development of uterine fibroids," commented study author Cynthia Morton (Brigham and Women's Hospital, Boston, Massachusetts) in a press statement.

"Identification of genetic risk factors may provide valuable insight into medical management."

Writing in the American Journal of Human Genetics, Morton and team report the results from a genome-wide association study carried out in two cohorts of white women from the Women's Genome Health Study Association Study (cases=746; controls=4487) and the Australian Cohort Association study (cases=484; controls=610).

One single nucleotide polymorphism, rs4247357, reached genome-wide significance for association with the condition (odds ratio=1.299; p=3.05x10^-8). It is located in a block of linkage disequilibrium on chromosome 17 (17q25.3) that spans three genes, namely, FASN, coiled-coil-domain-containing 57 (CCDC57), and solute-carrier family 16, member 3 (SLC16A3).

Further microarray analysis of tissue taken from women with fibroids revealed threefold higher levels of FAS compared with normal myometrial tissue. The team notes that higher than normal levels of FAS have also been implicated in various neoplasms and in tumor cell survival.

"Uterine leiomyomata, the most prevalent pelvic tumors in women of reproductive age, pose a major public health problem given their high frequency, associated morbidities, and most common indication for hysterectomies," say the authors.

"FASN represents the initial uterine leiomyomata risk allele identified in white women by a genome-wide, unbiased approach and opens a path to management and potential therapeutic intervention," they conclude.

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