Familial Clustering in the Polycystic Ovarian Syndrome

Lunde, O. C.; Magnus, Per; Sandvik, Leiv; Høglo, Sian

doi:10.1159/000293493

Cited by 172 publications

(85 citation statements)

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“…Familial clustering seen in this syndrome suggests contribution of a genetic component to its pathogenesis (12,13). Over the past decade, a number of candidate genes involved in steroidogenesis, insulin signaling pathway, gonadotropin secretion and chronic inflammation have been explored to identify the susceptibility genes for PCOS (14,15); however, the results so far have been inconclusive.…”

Section: Introductionmentioning

confidence: 99%

Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome

Mukherjee

Shaikh

Khavale

et al. 2009

European Journal of Endocrinology

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Objective: Polycystic ovary syndrome (PCOS) is a multigenic disorder, and insulin resistance is one of its hallmark features. Polymorphisms in exon 17 of insulin receptor (INSR) gene are reported to be associated with PCOS. We investigated this association in Indian women and its putative relationship with PCOS associated traits, which has not been explored so far. Methods: In this case control study, the polymorphisms were investigated by direct sequencing in 180 women with PCOS and 144 age matched controls. Clinical, anthropometric, biochemical, and hormonal parameters were also estimated. Results: The silent C/T polymorphism at His1058 in exon 17 of INSR was found to be present in our study population. The polymorphic genotype (CTCTT) was significantly associated with PCOS in lean women (c 2 Z8.493, dfZ1, PZ0.004). It showed association with higher fasting insulin levels (PZ0.02), homeostasis model assessment of insulin resistance (PZ0.005), free androgen index (PZ0.03), and lower quantitative insulin sensitivity check index (PZ0.004) in lean PCOS women. No other novel or known polymorphism was identified in exon 17 in this cohort. Conclusions: The study shows significant association of C/T polymorphism at His1058 of INSR with PCOS in the lean rather than obese Indian women. Its association with indices of insulin resistance and hyperandrogenemia is also seen in the same group. The findings strengthen the concept that pathogenesis of PCOS is different in lean and obese women.

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Section: Introductionmentioning

confidence: 99%

Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome

Mukherjee

Shaikh

Khavale

et al. 2009

European Journal of Endocrinology

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“…This has been investigated in several studies on PCOS phenotypes in different populations [17] and in family studies which indicated that a high number of female relatives are affected [18,19,20,21]. Most of these studies have used ovarian morphology [22,23] and endocrine abnormalities such as hyperandrogenaemia and anovulation to assign affected status [24].…”

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confidence: 99%

Prevalence of Type II diabetes mellitus and insulin resistance in parents of women with polycystic ovary syndrome

Sir-Petermann¹,

Ángel

Maliqueo

et al. 2002

Diabetologia

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Aims/hypothesis. Insulin resistance with increased risk of Type II (non-insulin-dependent) diabetes is a common feature of polycystic ovary syndrome (PCOS). To investigate antecedents of metabolic disorders in family members of patients with PCOS, we evaluated glucose tolerance and insulin resistance in parents of patients with PCOS compared to parents of healthy women. Methods. A total of 200 parents of women with clinical and hormonal evidence of PCOS (PCOSp) and 120 parents of healthy normally cycling women (HWp) were studied. A 75-g OGGT was performed and subjects were classified according to the World Health Organization (WHO) criteria (1999). Serum glucose and insulin were measured before the glucose load and 30, 60 and 120 min after. C-peptide and sex hormone-binding globulin were also determined before the glucose load. Insulin resistance was assessed by HOMA model and ISI composite.Results. The prevalence of Type II diabetes was 1.89-(1.06-3.38)-fold higher in PCOSp compared to HWp. Insulin resistance, evaluated by HOMA IR and ISI composite was also significantly higher in the PCOSp group compared to the HWp group. After both study groups were distributed by sex, and adjusted by age and BMI, the metabolic parameters were still significantly different between PCOSp and HWp. Conclusions/interpretation. The data suggest that parents of PCOS women exhibit insulin resistance and Type II diabetes more frequently than those of healthy women, thus constituting a high-risk group but an ideal cohort to detect and prevent the development of Type II diabetes. [Diabetologia (2002) 45:959-964] Keywords Type II diabetes, polycystic ovary syndrome, insulin resistance, family study.

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“…Familial aggregation of PCOS consistent with a genetic etiology has been well documented (4,5). The male reproductive phenotypes that have been proposed in PCOS families include abnormalities in hair distribution, such as increased hair growth (6), and more commonly balding (7)(8)(9)(10). This latter phenotype has been further refined to premature male balding defined as balding onset with an age of less than 30 yr (9,10).…”

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confidence: 99%

Elevated Dehydroepiandrosterone Sulfate Levels as the Reproductive Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

Legro

Kunselman

Demers

et al. 2002

The Journal of Clinical Endocrinology &Amp; Metabolism

131

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There is an inherited susceptibility to polycystic ovary syndrome (PCOS). Some investigators have suggested that premature male-pattern balding is a male phenotype in PCOS families, but this remains controversial. We recently reported evidence for an autosomal monogenic abnormality in ovarian and adrenal steroidogenesis in the sisters of women with PCOS. We performed this study to determine whether we could identify a clinical or biochemical phenotype in the brothers of women with PCOS. One hundred nineteen brothers of 87 unrelated women with PCOS and 68 weight-and ethnicity-comparable unrelated control men were examined and had fasting blood samples obtained. The odds of balding (Hamilton score ≥ V) did not differ in the brothers of PCOS women compared with control men. Brothers of women with PCOS had significantly elevated dehydroepiandrosterone sulfate (DHEAS) levels [brothers 3035 ± 1132 ng/ml (mean ± SD) vs. control men 2494 ± 1172 ng/ml; P < 0.05]. There was a significant positive linear relationship between DHEAS levels in PCOS probands and their brothers (r = 0.35; P = 0.001). There was no significant bimodal distribution in DHEAS levels, and there were no significant differences in other parameters in brothers of PCOS women with high DHEAS levels compared with those with low DHEAS levels. There is familial clustering of elevated DHEAS levels in the brothers of women with PCOS, suggesting that this is a genetic trait. This might reflect the same underlying defect in steroidogenesis that we found in the sisters of women with PCOS. Balding was not increased in the brothers of women with PCOS. We conclude that there is a biochemical reproductive endocrine phenotype in men in PCOS families.Polycystic Ovary Syndrome (PCOS) is among the most common endocrinopathies of premenopausal women, affecting 5-10% of this population (1, 2). The syndrome is characterized by hyperandrogenism and chronic anovulation in the absence of specific Copyright © 2002 HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript disorders of the pituitary, ovaries, or adrenal glands (3). Familial aggregation of PCOS consistent with a genetic etiology has been well documented (4, 5). The male reproductive phenotypes that have been proposed in PCOS families include abnormalities in hair distribution, such as increased hair growth (6), and more commonly balding (7-10). This latter phenotype has been further refined to premature male balding defined as balding onset with an age of less than 30 yr (9, 10). Others have noted abnormalities in LH levels in male members of PCOS kindreds (11).We recently reported elevated T and dehydroepiandrosterone levels in the sisters of women with PCOS (12). There was a bimodal distribution of biologically available T levels in these sisters consistent with a monogenic trait controlled by alleles of a gene at an autosomal locus (12). If there was variation in such a gene regulating steroidogenesis, it was our hypothesis that this should result in a reproductive phen...

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Familial Clustering in the Polycystic Ovarian Syndrome

Cited by 172 publications

References 9 publications

Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome

Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome

Prevalence of Type II diabetes mellitus and insulin resistance in parents of women with polycystic ovary syndrome

Elevated Dehydroepiandrosterone Sulfate Levels as the Reproductive Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

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