Variants in BET1L and TNRC6B associate with increasing fibroid volume and fibroid type among European Americans

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• 作者：Todd L. Edwards (1) (2) (3) (4)
  Katherine E. Hartmann (1) (2) (5)
  Digna R. Velez Edwards (1) (2) (3) (5)
  
• 刊名：Human Genetics
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：132
• 期：12
• 页码：1361-1369
• 全文大小：
• 作者单位：Todd L. Edwards (1) (2) (3) (4)
  Katherine E. Hartmann (1) (2) (5)
  Digna R. Velez Edwards (1) (2) (3) (5)
  
  1. Vanderbilt Epidemiology Center, Vanderbilt University, 2525 West End Ave., Suite 600 6th Floor, Nashville, TN, 37203, USA
  2. Institute for Medicine and Public Health, Vanderbilt University, Nashville, USA
  3. Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA
  4. Division of Epidemiology, Department of Medicine, Vanderbilt University, Nashville, TN, USA
  5. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, USA
  
• ISSN：1432-1203

文摘

Uterine fibroids (UFs) affect 77% of women by menopause and account for $9.4billion in yearly healthcare costs. We recently replicated findings from the first UF genome-wide association study (GWAS), conducted in the Japanese. Here we tested these GWAS-discovered SNPs for association with UF characteristics to further assess whether risk varies by sub-phenotypes of UFs. Women were enrolled in Right from the Start (RFTS) and the BioVU DNA repository (BioVU). UF status was determined by pelvic imaging. We tested the top GWAS-associated SNPs for association with UF characteristics (RFTS: type, number, volume; BioVU: type) using covariate adjusted logistic and linear regression. We also combined association results of UF type using meta-analysis. 456 European American (EA) cases and 1,549 controls were examined. Trinucleotide repeat containing 6B (TNRC6B) rs12484776 associated with volume in RFTS (=0.40, 95% CI 0.05.75, p=0.024). RFTS analyses evaluating stratified quartiles of volume showed the strongest OR at rs12484776 for the largest volume (16.679.1cc, odds ratio (OR)=2.19, 95% confidence interval (CI) 1.07.46, p=0.031). Meta-analysis showed a strong association at blocked early in transport 1 homolog (BET1L) rs2280543 for intramural UFs (meta-OR=0.51, standard error (SE)=0.14, Q=0.590, I=0, p=2.48106), which is stronger than the overall association with UF risk. This study is the first to evaluate these SNPs for association with UF characteristics and suggests these genes associate with increasing UF volume and protection from intramural UF in EAs.