Evaluation of polymorphisms in predicted target sites for micro RNAs differentially expressed in endometriosis

Zhao, Zhen Zhen, Croft, Larry, Nyholt, Dale R., Chapman, Brett, Treloar, Susan A., Hull, M. Louise, & Montgomery, Grant W. (2011) Evaluation of polymorphisms in predicted target sites for micro RNAs differentially expressed in endometriosis. Molecular Human Reproduction, 17(2), pp. 92-103.

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Previous microarray analyses identified 22 microRNAs (miRNAs) differentially expressed in paired ectopic and eutopic endometrium of women with and without endometriosis. To investigate further the role of these miRNAs in women with endometriosis, we conducted an association study aiming to explore the relationship between endometriosis risk and single-nucleotide polymorphisms (SNPs) in miRNA target sites for these differentially expressed miRNAs. A panel of 102 SNPs in the predicted miRNA binding sites were evaluated for an endometriosis association study and an ingenuity pathway analysis was performed. Fourteen rare variants were identified in this study. We found SNP rs14647 in the Wolf-Hirschhorn syndrome candidate gene1 (WHSC1) 3'UTR (untranslated region) was associated with endometriosis-related infertility presenting an odds ratio of 12.2 (95% confidence interval = 2.4-60.7, P = 9.03 x 10(-5)). SNP haplotype AGG in the solute carrier family 22, member 23 (SLC22A23) 3'UTR was associated with endometriosis-related infertility and more severe disease. With the individual genotyping data, ingenuity pathways analysis identified the tumour necrosis factor and cyclin-dependant kinase inhibitor as major factors in the molecular pathways. Significant associations between WHSC1 alleles and endometriosis-related infertility and SLC22A23 haplotypes and the disease severe stage were identified. These findings may help focus future research on subphenotypes of this disease. Replication studies in independent large sample sets to confirm and characterize the involvement of the gene variation in the pathogenesis of endometriosis are needed.

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20 citations in Scopus
17 citations in Web of Science®
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ID Code: 91909
Item Type: Journal Article
Refereed: Yes
Keywords: Adult, Cyclin-Dependent Kinase Inhibitor Proteins/genetics, Endometriosis/*genetics, Endometrium/*metabolism, Female, *Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, MicroRNAs/*genetics, Middle Aged, Polymerase Chain Reaction, *Polymorphism, Single Nucleotide, Risk, Sequence Alignment, Tumor Necrosis Factor-alpha/genetics, Wolf-Hirschhorn Syndrome/genetics
DOI: 10.1093/molehr/gaq084
ISSN: 1460-2407
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 17 Jan 2016 23:19
Last Modified: 26 Jun 2017 19:01

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