Dr. Brahim Aissani, research assistant professor in the department of epidemiology at the University of Alabama at Birmingham, recently assessed the association of 56 candidate single nucleotide polymorphisms (SNPs) identified in two published genome-wide association studies (GWAS) of uterine leiomyoma (UL), or fibroids — Riken Center for Integrative Medical Sciences and the Women’s Genome Health Study (WGHS) — with the risk and tumor size in the multi-ethnic National Institute of Environmental Health Sciences Uterine Fibroid Study (NIEHS-UFS). Co-investigators in the study are Dr. Kui Zhang, associate professor in UAB’s department of biostatistics, section on statistical genetics, and department colleague Dr. Howard W. Wiener.
“The selected SNPs were genotyped in 916 premenopausal women of African American (AA) or European American (EA) descent and their association with the outcomes was evaluated in race-stratified models and in meta-analysis of risk in NIEHS-UFS and discovery and replication GWAS in the Japanese population,” explains Dr. Aissani.
The researchers report “moderate associations of variant rs4954368 in THSD7B (thrombospondin, type I, domain containing 7B) with tumor size in pooled analysis of AA and EA samples (P = 0.004), and at TNRC6B (trinucleotide repeat containing 6B) variants rs138039 and rs139909 in EA (P = 0.001 and P = 0.008, respectively). The most significant associations with risk in meta-analysis were observed at TNRC6B variants rs739182 (P = 3.7 x 10-10) and rs2072858 (P = 1.1 x 10-9) and were stronger than those reported in the discovery GWAS (P =2.01 x 10-8 and P = 2.58 x 10-8, respectively).”
Results failed to replicate the associations reported for CCDC57 and FASN in WGHS. Consistent with published findings in the first replication studies — Right From the Start Study (RFTS) and the BioVU DNA repository — the team was able to present independent evidence for association of TNRC6B with risk and size of UL. The TNRC6 paralogs encode members of the GW182 protein family, which are essential components of the miRNA pathway previously implicated in the pathogenesis of uterine fibroids. This study is the first to report a “replicated association of THSD7B with UL, albeit with tumor size and not with risk.” Thrombospondins are potent inhibitors of angiogenesis and variants affecting their expression or structure may lead to uncontrolled tumor growth.
“Evaluation of GWAS Candidate Susceptibility Loci for Uterine Leiomyoma in the Multi-ethnic NIEHS Uterine Fibroid Study” was published in July in the journal Frontiers in Genetics.