OBJECTIVE

To conduct a follow-up association mapping to independent genome-wide linkage and admixture mapping studies of uterine leiomyoma.

DESIGN

Case-control, cross-sectional study.

SETTING

Not applicable.

PATIENT(S): A total of 1,045 premenopausal North American participants in the National Institute of Environmental Health Sciences Uterine Fibroid Study.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): We genotyped 2,772 single-nucleotide polymorphisms from candidate genes located in peaks of linkage (2q37, 3p21, 5p13, 10p11, 11p15, 12q14, and 17q25) or admixture linkage disequilibrium (2q37, 4p16.1, and 10q26) mapping and reported to have regulated expression in uterine fibroids.

RESULT(S): We report significant associations of variant members of the collagen gene family with risk and tumor size, including missense variants in COL6A3 and COL13A, with replications in African American and European American study groups. Furthermore, the cell-matrix Rho GTPase-encoding ARHGAP26 gene, and MAN1C1, a gene encoding a Golgi mannosidase involved in the maturation of procollagens, emerged as new candidate uterine leiomyoma genes affecting both risk and tumor size.

CONCLUSION(S): Our data converge onto a possible model of uterine leiomyoma pathogenesis resulting from altered regulation, maintenance, and/or renewal of the extracellular matrix.