Absence of insulin receptor gene mutations in three insulin-resistant women with the polycystic ovary syndrome

Sorbara, Lynn; Tang, Zhichun; Cama, Alessandro; Xia, Jing; Schenker, Esther; Kohanski, Ronald A.; Poretsky, Leonid; Koller, Elizabeth A.; Taylor, Simeon I.; Dunaif, Andrea

doi:10.1016/0026-0495(94)90018-3

Cited by 65 publications

(26 citation statements)

References 41 publications

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“…Several studies have sought, but failed to find, mutations in the INSR coding region of patients with PCOS (14,17,19,(21)(22)(23). Our findings in this region are consistent with previous (1999) studies in that we also do not find evidence for linkage between PCOS and the INSR.…”

Section: Tdtsupporting

confidence: 83%

“…These include the metabolic or regulatory pathways of steroid hormone synthesis (10,11), regulatory pathways of gonadotropin action (12), the insulin-signaling pathway (13)(14)(15), and pathways regulating body weight (16). Several genes from these pathways have been tested as candidate genes for PCOS (10,11,(17)(18)(19)(20)(21)(22)(23). In particular, in the insulin receptor gene (INSR), mutations have been identified in several rare syndromes that, like PCOS, are characterized by hyperandrogenism and insulin-resistant diabetes mellitus.…”

mentioning

confidence: 99%

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Thirty-seven candidate genes for polycystic ovary syndrome: Strongest evidence for linkage is with follistatin

Urbanek

Legro

Driscoll

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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454

284

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Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72%; 2 ‫؍‬ 12.97; nominal P ‫؍‬ 3.2 ؋ 10 ؊4 ). After correction for multiple testing (33 tests), the follistatin findings were still highly significant (P c ‫؍‬ 0.01). Although the linkage results for CYP11A were also nominally significant (P ‫؍‬ 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission͞disequilibrium test ( 2 > 3.84; nominal P < 0.05). The strongest effect in the transmission͞disequilibrium test was observed in the INSR region (D19S884; allele 5; 2 ‫؍‬ 8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study.

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Section: Tdtsupporting

confidence: 83%

mentioning

confidence: 99%

Thirty-seven candidate genes for polycystic ovary syndrome: Strongest evidence for linkage is with follistatin

Urbanek

Legro

Driscoll

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

454

284

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“…The hypothesis for the existence of a postreceptor defect in insulin action in PCOS is also consistent with reports of molecular studies found no structural abnormality in the insulin receptor (Conway et al ., 1994;Sorbara et al ., 1994;Talbot et al ., 1996).…”

Section: Insulin Resistancementioning

confidence: 99%

The pathophysiology of polycystic ovary syndrome

Tsilchorozidou

Overton

Conway

2003

Clinical Endocrinology

232

167

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“…No mutations have been detected in the coding region of the insulin receptor gene in women with PCOS (Sorbara et al, 1994;Dunaif et af., 1995;Talbot et al, 1996). Moreover, immunoprecipitation and mixing experiments have suggested that a factor extrinsic to the insulin receptor -presumably, a serine kinase -is responsible for the abnormal pattern of phosphorylation in PCOS fibroblasts (Dunaif et al, 1995).…”

Section: Insulin Action In Pcos Fibroblastsmentioning

confidence: 99%

Insulin Resistance in Polycystic Ovary Syndrome: Progress and Paradoxes

Venkatesan¹

2001

Recent Progress in Hormone Research

135

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Over the past 20 years, it has been clearly documented that I) polycystic ovary syndrome (PCOS) has major metabolic sequelae related to insulin resistance and 2) insulin resistance plays an important role in the pathogenesis of the reproductive abnormalities of the disorder, Women with PCOS are at significantly increased risk of developing type 2 diabetes mellitus (DM). Studies in isolated adipocytes and in cultured skin tibroblasts from PCOS women have demonstrated intrinsic postbinding defects in insulin-mediated glucose metabolism.

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Absence of insulin receptor gene mutations in three insulin-resistant women with the polycystic ovary syndrome

Cited by 65 publications

References 41 publications

Thirty-seven candidate genes for polycystic ovary syndrome: Strongest evidence for linkage is with follistatin

Thirty-seven candidate genes for polycystic ovary syndrome: Strongest evidence for linkage is with follistatin

The pathophysiology of polycystic ovary syndrome

Insulin Resistance in Polycystic Ovary Syndrome: Progress and Paradoxes

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