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dc.contributor.authorProdoehl, Mark J
dc.contributor.authorHatzirodos, Nicholas
dc.contributor.authorIrving-Rodgers, Helen F
dc.contributor.authorZhao, Zhen Z
dc.contributor.authorPainter, Jodie N
dc.contributor.authorHickey, Theresa E
dc.contributor.authorGibson, Mark A
dc.contributor.authorRainey, William E
dc.contributor.authorCarr, Bruce R
dc.contributor.authorMason, Helen D
dc.contributor.authorNorman, Robert J
dc.contributor.authorMontgomery, Grant W
dc.contributor.authorRodgers, Raymond J
dc.date.accessioned2010-09-24T22:03:25Z
dc.date.available2010-09-24T22:03:25Z
dc.date.issued2009-11-13en_US
dc.identifier.citationMol Hum Reprod. 2009 Dec 19; 15(12):829-841en_US
dc.identifier.issn1460-2407en_US
dc.identifier.pmid19692420en_US
dc.identifier.doi10.1093/molehr/gap072en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/132
dc.description.abstractSeveral 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)-beta-binding proteins (LTBP) and thereby control the bioactivity of TGFbetas. TGFbetas 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.
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshChromosome Mappingen_US
dc.subject.meshChromosomes, Human, Pair 19en_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Expressionen_US
dc.subject.meshGenetic Predisposition to Diseaseen_US
dc.subject.meshGenotypeen_US
dc.subject.meshHaplotypesen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMicrofilament Proteins / genetics / metabolismen_US
dc.subject.meshMicrosatellite Repeatsen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshOvary / physiologyen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshPolycystic Ovary Syndrome / genetics / metabolismen_US
dc.subject.meshPolymorphism, Single Nucleotideen_US
dc.subject.meshProtein Isoforms / genetics / metabolismen_US
dc.subject.meshRNA, Messenger / metabolismen_US
dc.titleGenetic and gene expression analyses of the polycystic ovary syndrome candidate gene fibrillin-3 and other fibrillin family members in human ovaries.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC2776474en_US
dc.contributor.corporatenameDepartment of Physiologyen_US
refterms.dateFOA2019-04-09T16:25:49Z
html.description.abstractSeveral 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)-beta-binding proteins (LTBP) and thereby control the bioactivity of TGFbetas. TGFbetas 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.


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