FASN, dietary fat intake, and risk of uterine leiomyomata in the Black Women's Health Study
Rs4247357 was related to an increased risk of uterine leiomyomata in the Black Women’s Health Study, but only among African American women with 40% European ancestry. The association was strongest among women in the lowest tertile of dietary fat intake.
Volume 106, Issue 5, Pages 1136-1141
Lauren A. Wise, Sc.D., Julie R. Palmer, Sc.D., Lynn Rosenberg, Sc.D., Stephen A. Haddad, M.Sc., Edward A. Ruiz-Narváez, Sc.D.
To replicate results from a previous genome-wide association study of European ancestry women, in which a positive association was found between uterine leiomyomata (UL) and rs4247357, a single-nucleotide polymorphism located near the fatty acid synthase (FASN) gene.
Prospective cohort study.
African-American women aged 23–50 years, who were premenopausal and had an intact uterus in 1997.
Main Outcome Measure(s)
We genotyped rs4247357 among 2,301 incident UL cases and 3,005 controls from the Black Women's Health Study (1997-2011). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression with control for age, geographic region of residence, and percent European ancestry using a panel of validated ancestry informative markers.
Overall, rs4247357 was not associated with UL risk. Relative to the CC genotype, ORs were 1.04 (95% CI 0.92–1.19) for the AC genotype and 1.09 (95% CI 0.93–1.29) for the AA genotype. A positive association was found, however, among those with higher European ancestry (≥40%). Relative to the CC genotype, ORs were 2.03 (95% CI 1.12–3.69) for the AC genotype and 2.44 (95% CI 1.20–4.96) for the AA genotype. Dietary fat intake also appeared to modify the FASN–UL association.
Although there was little overall association between rs4247357 and UL risk, a positive association was observed among women with ≥40% European ancestry. Direct sequencing of this genomic region might be warranted to determine whether rs4247357, or some other variant, is causally related to UL.