Wise Lauren A, Palmer Julie R, Rosenberg Lynn, Haddad Stephen A, Ruiz-Narváez Edward A
Slone Epidemiology Center at Boston University, Boston, Massachusetts; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.
Slone Epidemiology Center at Boston University, Boston, Massachusetts.
Fertil Steril. 2016 Oct;106(5):1136-1141. doi: 10.1016/j.fertnstert.2016.06.019. Epub 2016 Jun 30.
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.
Not applicable.
PATIENT(S): African-American women aged 23-50 years, who were premenopausal and had an intact uterus in 1997.
INTERVENTION(S): None.
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.
RESULT(S): 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.
CONCLUSION(S): 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.
重复之前一项针对欧洲裔女性的全基因组关联研究的结果，该研究发现子宫肌瘤（UL）与位于脂肪酸合酶（FASN）基因附近的单核苷酸多态性rs4247357之间存在正相关。
前瞻性队列研究。
不适用。
1997年年龄在23至50岁之间、处于绝经前且子宫完整的非裔美国女性。
无。
我们对来自黑人女性健康研究（1997 - 2011年）的2301例新发UL病例和3005例对照进行了rs4247357基因分型。使用逻辑回归估计比值比（OR）和95%置信区间（CI），并通过一组经过验证的祖先信息标记物对年龄、居住地理区域和欧洲血统百分比进行控制。
总体而言，rs4247357与UL风险无关。相对于CC基因型，AC基因型的OR为1.04（95%CI 0.92 - 1.19），AA基因型的OR为1.09（95%CI 0.93 - 1.29）。然而，在欧洲血统较高（≥40%）的人群中发现了正相关。相对于CC基因型，AC基因型的OR为2.03（95%CI 1.12 - 3.69），AA基因型的OR为2.44（95%CI 1.20 - 4.96）。膳食脂肪摄入似乎也会改变FASN与UL之间的关联。
尽管rs4247357与UL风险之间总体关联不大，但在欧洲血统≥40%的女性中观察到了正相关。可能有必要对该基因组区域进行直接测序，以确定rs4247357或其他一些变异是否与UL存在因果关系。
