ECE2017 Eposter Presentations: Reproductive Endocrinology Female Reproduction (62 abstracts)
Influence of peroxisome proliferator-activated receptor (PPAR)-γ exon 2 (Pro12Ala) and exon 6 (His447His) and Gly972Arg insulin receptor substrate (IRS)-1 polymorphisms on insulin resistance (IR) and beta cell function in Southern Mediterranean women with polycystic ovary syndrome (PCOS)
Giuseppina T Russo 1 , Maria Angela Pappalardo 2 , Annalisa Giandalia 1 , Elisabetta L Romeo 1 , Angela Alibrandi 3 , Flavia Di Bari 1 , Roberto Vita 1 , Domenico Cucinotta 1 & Salvatore Benvenga 1,
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; 2Centro Polispecialistico Rizzo, Torregrotta, Messina, Italy; 3Department of Economicsm University of Messina, Messina, Italy; 4Interdepartmental Program of Molecular and Clinical Endocrinology, and Women’s Endocrine Health, University hospital Policlinico G. Martino, Messina, Italy.
The Pro12Ala and His447His polymorphisms of PPAR-γ, and Gly972Arg polymorphism of IRS-1 have been implicated in insulin resistance (IR) and adiposity. In this study, we investigated the possible influence of these polymorphisms on metabolic features of 53 PCOS women compared with 26 healthy women (controls). All women underwent a clinical, anthropometric and biochemical evaluation, including a 75-g oral glucose tolerance test; insulin secretion and sensitivity indices were calculated. In the two groups, frequencies of PPARγ polymorphisms did not differ from those predicted by the Hardy-Weinberg equilibrium. Instead, the IRS-1 Gly972Arg allele was significantly more frequent in the PCOS group compared to controls. The frequency of different allelic combinations was unequal in the two groups, with IRS1+/exon2−/exon6− detected in 66% of PCOS and IRS-1−/exon2−/exon6− in 73% of controls. In PCOS women, the IRS-1 Gly972Arg allele was associated with lower E2 levels (P=0.030), while the PPARγ Pro12Ala allele with lower free-testosterone levels (P=0.021). No other relationships were noted. When compared with wild-type women, in PCOS group, IR was: 1) trendwise greater in carriers of the variant allele in IRS-1 gene (borderline higher HOMA-IR, insulinogenic and disposition indices); 2) trendwise lower in carriers of the variant PPAR-γ exon6 allele (lower HOMA-IR and higher Matsuda index, lower insulinogenic and disposition indices); 3) lower (P<0.01) in carriers of the PPAR-γ exon2 variant (lower HOMA-IR values and higher insulinogenic and disposition indices). Furthermore, within the IRS-1+/PPAR-γ-exon2− PCOS women, PPAR-γ- exon6+ women had higher Matsuda index (P=0.03) compared with the noncarriers (PPAR-γ-exon6−). Our data support the protective influence of PPAR-γ-exon2 and exon6 variants on IR and beta-cell function, whereas IRS-1 polymorphism is associated with a more unfavorable metabolic profile. However, these associations do not fully explain the high metabolic risk PCOS-associated.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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