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

Prodoehl, MJ; Hatzirodos, N; Irving-Rodgers, HF; Zhao, ZZ; Painter, JN; Hickey, TE; Gibson, MA; Rainey, WE; Carr, BR; Mason, HD; et al. Prodoehl, MJ; Hatzirodos, N; Irving-Rodgers, HF; Zhao, ZZ; Painter, JN; Hickey, TE; Gibson, MA; Rainey, WE; Carr, BR; Mason, HD; Norman, RJ; Montgomery, GW; Rodgers, RJ (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). 829 - 841. ISSN 1360-9947 https://doi.org/10.1093/molehr/gap072
SGUL Authors: Mason, Helen Diane

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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.

Item Type: Article
Additional Information: © The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Cell Line, Tumor, Cells, Cultured, Chromosome Mapping, Chromosomes, Human, Pair 19, Female, Gene Expression, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Male, Microfilament Proteins, Microsatellite Repeats, Molecular Sequence Data, Ovary, Phenotype, Polycystic Ovary Syndrome, Polymorphism, Single Nucleotide, Protein Isoforms, RNA, Messenger, Science & Technology, Life Sciences & Biomedicine, Developmental Biology, Reproductive Biology, DEVELOPMENTAL BIOLOGY, REPRODUCTIVE BIOLOGY, fibrillin, latent-transforming growth factor beta-binding protein, polycystic ovary syndrome, ovary, GROWTH-FACTOR-BETA, INSULIN-RESISTANCE, BINDING-PROTEIN, MARFAN-SYNDROME, TGF-BETA, FOLLICULAR-FLUID, FOLLISTATIN GENE, TNF-ALPHA, WOMEN, ASSOCIATION, Obstetrics & Reproductive Medicine, 1114 Paediatrics And Reproductive Medicine, 0606 Physiology, 1103 Clinical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: MOLECULAR HUMAN REPRODUCTION
ISSN: 1360-9947
Related URLs:
Dates:
DateEvent
19 August 2009Published
Web of Science ID: WOS:000271819000009
URI: http://openaccess.sgul.ac.uk/id/eprint/107184
Publisher's version: https://doi.org/10.1093/molehr/gap072

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