PMID- 19926323
OWN - NLM
STAT- MEDLINE
DCOM- 20100503
LR  - 20111117
IS  - 1096-7206 (Electronic)
IS  - 1096-7192 (Linking)
VI  - 99
IP  - 2
DP  - 2010 Feb
TI  - Polymorphisms of the insulin receptor and the insulin receptor substrates genes 
      in polycystic ovary syndrome: a Mendelian randomization meta-analysis.
PG  - 174-83
LID - 10.1016/j.ymgme.2009.10.013 [doi]
AB  - Polycystic ovary syndrome (PCOS) is a heterogeneous condition with unknown 
      aetiology which is considered to be the most common endocrine disorder in women 
      of reproductive age. In this work we investigated the association of insulin 
      receptor (IotaNSR) and insulin receptor substrates (IRSs) polymorphisms with the 
      risk of developing PCOS. The meta-analysis of eleven studies (889 cases, 1303 
      controls) yielded a significant association for IRS-1 Gly972Arg (G972R) 
      polymorphism concerning the GR vs. GG genotype (OR: 1.77, 95% CI: 1.28, 2.45), 
      with no between-studies heterogeneity. Concerning IotaNSR His1058 C/T, the 
      meta-analysis of eight studies (795 cases, 576 controls) found no significant 
      evidence for association with PCOS (OR for the TT+CT vs. CC comparison equal to 
      1.28 with 95% CI: 0.88, 1.85) and a moderate between studies variability 
      (I(2)=44.6%). No evidence for publication bias was found in these meta-analyses. 
      Following a multivariate Mendelian randomization approach, the overall OR was 
      unaffected but the overall mean difference of fasting insulin levels between 
      carriers of GR and RR genotypes in controls was significant (2.18, 95% CI: 0.36, 
      4.01). These results suggest that IRS-1 Gly972Arg polymorphism is significantly 
      associated with the risk of developing PCOS and that this association is 
      primarily mediated by increasing the levels of fasting insulin. The particular 
      polymorphism is located in a region nearby two phosphorylation sites that 
      interact physically with INSR and PI 3-kinase and there is enough evidence from 
      the literature suggesting that the Arg972 variant is associated with decreased PI 
      3-kinase activity and impaired insulin-stimulated signaling.
CI  - Copyright (c) 2009 Elsevier Inc. All rights reserved.
FAU - Ioannidis, Anastasios
AU  - Ioannidis A
AD  - Department of Computer Science and Biomedical Informatics, University of Central 
      Greece, Papasiopoulou 2-4, 351 00 Lamia, Greece.
FAU - Ikonomi, Eleni
AU  - Ikonomi E
FAU - Dimou, Niki L
AU  - Dimou NL
FAU - Douma, Lelouda
AU  - Douma L
FAU - Bagos, Pantelis G
AU  - Bagos PG
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20091022
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Fasting/blood
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Insulin/blood
MH  - Insulin Receptor Substrate Proteins/*genetics
MH  - *Mendelian Randomization Analysis
MH  - Models, Genetic
MH  - Polycystic Ovary Syndrome/blood/*genetics
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Receptor, Insulin/*genetics
EDAT- 2009/11/21 06:00
MHDA- 2010/05/04 06:00
CRDT- 2009/11/21 06:00
PHST- 2009/08/01 00:00 [received]
PHST- 2009/10/17 00:00 [revised]
PHST- 2009/10/18 00:00 [accepted]
PHST- 2009/11/21 06:00 [entrez]
PHST- 2009/11/21 06:00 [pubmed]
PHST- 2010/05/04 06:00 [medline]
AID - S1096-7192(09)00297-2 [pii]
AID - 10.1016/j.ymgme.2009.10.013 [doi]
PST - ppublish
SO  - Mol Genet Metab. 2010 Feb;99(2):174-83. doi: 10.1016/j.ymgme.2009.10.013. Epub 
      2009 Oct 22.