Genetic and gene expression analyses of the polycystic ovary syndrome candidate gene fibrillin-3 and other fibrillin family members in human ovaries

Prodoehl, Mark, Hatzirodos, Nicholas, Irving-Rodgers, Helen, Zhao, Zhen Zhen, Painter, Jodie, Hickey, Theresa, Gibson, Mark, Rainey, William, Carr, Bruce, Mason, Helen, Norman, Robert, Montgomery, Grant, & Rodgers, Raymond (2009) Genetic and gene expression analyses of the polycystic ovary syndrome candidate gene fibrillin-3 and other fibrillin family members in human ovaries. Molecular Human Reproduction, 15(12), pp. 829-841.

View at publisher (open access)

Abstract

Several studies have demonstrated an association between polycystic ovary syndrome (PCOS) and the dinucleotide repeat microsatellite marker D19S884, which is located in intron 55 of the fibrillin-3 (FBN3) gene. Fibrillins, including FBN1 and 2, interact with latent transforming growth factor (TGF)-β-binding proteins (LTBP) and thereby control the bioactivity of TGFβs. TGFβs stimulate fibroblast replication and collagen production. The PCOS ovarian phenotype includes increased stromal collagen and expansion of the ovarian cortex, features feasibly influenced by abnormal fibrillin expression. To examine a possible role of fibrillins in PCOS, particularly FBN3, we undertook tagging and functional single nucleotide polymorphism (SNP) analysis (32 SNPs including 10 that generate non-synonymous amino acid changes) using DNA from 173 PCOS patients and 194 controls. No SNP showed a significant association with PCOS and alleles of most SNPs showed almost identical population frequencies between PCOS and control subjects. No significant differences were observed for microsatellite D19S884. In human PCO stroma/cortex (n = 4) and non-PCO ovarian stroma (n = 9), follicles (n = 3) and corpora lutea (n = 3) and in human ovarian cancer cell lines (KGN, SKOV-3, OVCAR-3, OVCAR-5), FBN1 mRNA levels were approximately 100 times greater than FBN2 and 200–1000-fold greater than FBN3. Expression of LTBP-1 mRNA was 3-fold greater than LTBP-2. We conclude that FBN3 appears to have little involvement in PCOS but cannot rule out that other markers in the region of chromosome 19p13.2 are associated with PCOS or that FBN3 expression occurs in other organs and that this may be influencing the PCOS phenotype.

Impact and interest:

23 citations in Scopus
Search Google Scholar™
19 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 44481
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Keywords: fibrillin, latent-transforming growth factor b-binding protein, polycystic ovary syndrome, ovary
DOI: 10.1093/molehr/gap072
ISSN: 1360-9947
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PAEDIATRICS AND REPRODUCTIVE MEDICINE (111400)
Deposited On: 24 Aug 2011 22:11
Last Modified: 05 Feb 2015 03:35

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page