Objective
To conduct a follow-up association mapping to independent genome-wide linkage and admixture mapping studies of uterine leiomyoma.
Design
Case-control study.
Setting
Cross sectional study.
Patients
A total of 1,045 premenopausal North American women participants to the NIEHS uterine fibroid study.
Intervention(s)
None.
Main Outcome Measure(s)
We genotyped 2,772 single nucleotide polymorphisms from candidate genes located in peaks from linkage mapping (2q37, 3p21, 5p13, 10p11, 11p15, 12q14, 17q25) or admixture linkage disequilibrium mapping (2q37, 4p16.1, 10q26) and reported to have regulated expression in uterine fibroids.
Results
We report significant associations of variant members of the collagen gene family with the risk and tumor size, including missense variants in COL6A3 and COL13A, with replications in the African 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 UL genes affecting both the risk and tumor size.
Conclusion
Our data converge onto a model of UL pathogenesis possibly resulting from altered regulation, maintenance and/or renewal of the extracellular matrix.