Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome

Sam, Susan; Legro, Richard S.; Essah, Paulina A.; Apridonidze, Teimuraz; Dunaif, Andrea

doi:10.1073/pnas.0602025103

Cited by 91 publications

(62 citation statements)

References 49 publications

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“…In addition, the prevalence of metabolic syndrome is increased in these groups (3,9). Further, increased LDL levels and metabolic syndrome are significantly associated with hyperandrogenemia, suggesting that the cardinal reproductive feature of the syndrome plays a direct role in the etiology of the associated metabolic abnormalities (3,9). Consistent with this hypothesis, the PCOS susceptibility allele is associated with markers of insulin resistance in women with PCOS (5).…”

supporting

confidence: 72%

“…Elevated LDL cholesterol levels are the most consistent lipid abnormality in affected women as well as in their sisters and mothers (3,8 -10). In addition, the prevalence of metabolic syndrome is increased in these groups (3,9). Further, increased LDL levels and metabolic syndrome are significantly associated with hyperandrogenemia, suggesting that the cardinal reproductive feature of the syndrome plays a direct role in the etiology of the associated metabolic abnormalities (3,9).…”

mentioning

confidence: 88%

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Metabolic Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

et al. 2008

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OBJECTIVE -Hyperandrogenemia, insulin resistance, and dyslipidemia demonstrate familial aggregation in the female first-degree relatives of women with polycystic ovary syndrome (PCOS), suggesting that these defects are heritable. Hyperandrogenemia also appears to be the male reproductive phenotype. We performed this study to test the hypothesis that brothers of women with PCOS have metabolic defects similar to those of their proband sisters.RESEARCH DESIGN AND METHODS -This was a prospective case-control study performed at four academic medical centers in the U.S. Fasting blood was obtained from 196 non-Hispanic white brothers of women with PCOS and 169 control men of age, BMI, and ethnicity comparable to those of brothers. A separate analysis was performed by study site to assess potential regional variations in metabolic parameters.RESULTS -Overall, brothers of women with PCOS had significantly higher total (P ϭ 0.001) and LDL cholesterol (P ϭ 0.01) as well as triglyceride levels (P ϭ 0.01) compared with control men, although there were regional variations in these differences. There were significant positive correlations between brothers and their sisters with PCOS for total ( ϭ 0.2, P ϭ 0.009) and LDL cholesterol ( ϭ 0.3, P ϭ 0.001) and triglyceride ( ϭ 0.2, P ϭ 0.05) levels. Brothers also had significantly higher fasting insulin levels and homeostatic index of insulin resistance (P ϭ 0.02 for both comparisons) compared with control men.CONCLUSIONS -Brothers of women with PCOS have dyslipidemia as well as evidence for insulin resistance similar to that of their proband sisters with PCOS. These findings are consistent with the hypothesis that some metabolic abnormalities in PCOS are heritable and are not sex specific. Diabetes Care 31:1237-1241, 2008P olycystic ovary syndrome (PCOS) is a complex genetic disorder that affects ϳ7% of premenopausal women (1). It is the leading cause of anovulatory infertility and an important risk factor for type 2 diabetes and metabolic syndrome in young adult women as well as in adolescent girls (1). The major reproductive phenotype is hyperandrogenemia and up to 40% of premenopausal sisters are affected (2). Moreover, mothers (3) and brothers (4) also have elevated mean androgen levels compared with control subjects of comparable sex, age, weight, and ethnicity. We have identified one PCOS susceptibility allele within a dinucleotide repeat (D19S884) in intron 55 of the fibrillin-3 gene on chromosome 19p13.2 that is linked and associated with hyperandrogenemia (5).Abnormalities in insulin action and secretion, glucose tolerance, and lipid levels also demonstrate familial aggregation in first-degree female relatives of women with PCOS (3,6 -9). Elevated LDL cholesterol levels are the most consistent lipid abnormality in affected women as well as in their sisters and mothers (3,8 -10). In addition, the prevalence of metabolic syndrome is increased in these groups (3,9). Further, increased LDL levels and metabolic syndrome are significantly associated with hyperandrogenemia, sugg...

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confidence: 72%

mentioning

confidence: 88%

Metabolic Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

et al. 2008

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“…Our studies indicate that mothers and brothers also have elevated LDL levels and evidence for insulin resistance [102]. Therefore, reproductive and metabolic abnormalities track together in PCOS families suggesting that they may reflect variation in the same gene or in closely linked genes, be causally related, or have a common pathogenesis.…”

Section: Evidence For a Genetic Susceptibility To Pcosmentioning

confidence: 88%

Reproduction and Metabolism: Insights from Polycystic Ovary Syndrome

Jasti

Dunaif

2012

Endocrinol Metab

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“…Moini et al [25] reported a significantly increased prevalence of maternal DM in the PCOS group than the control group, and a maternal history of DM was more predictive than a paternal history of DM. Moreover, mothers of women with PCOS had a higher HOMA-IR, an increased prevalence of MetS, and an elevated risk for CHD [26]. Whether paternal or maternal inheritance underlies PCOS has been a matter of controversy and varies in different populations and races.…”

Section: Discussionmentioning

confidence: 99%

Paternal history of diabetes mellitus and hypertension affects the prevalence and phenotype of PCOS

Chen

Zhang

Zhao

et al. 2015

J Assist Reprod Genet

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Purpose The purpose of the present study is to determine if paternal or maternal history of diabetes mellitus (DM) and hypertension (HT) contributes to the prevalence and phenotype of polycystic ovary syndrome (PCOS). Methods We performed an epidemiologic study about PCOS from four districts in Beijing, China, between 2008 and 2009. Parental histories of DM and HT were collected, and the basic characteristics and serum indices of 123 PCOS patients and 718 non-PCOS controls were tested. Results The prevalence of a parental history of DM and HT was significantly higher in PCOS patients than non-PCOS women (17.1 % vs. 9.2 % and 42.3 % vs. 26.0 %, P<0.05, respectively). When paternal history was separated from maternal history, only a paternal history of DM and HT reached statistical significance between PCOS and non-PCOS patients (odds ratio (OR)=3.42, 95 % confidence interval (CI)=1.69-6.91; OR=2.50, 95 % CI=1.58-3.93, respectively). A paternal history of both DM and HT was significantly associated with sex hormone-binding globulin, fasting plasma glucose, and fasting insulin levels, the free androgen index, and the homeostatic model assessment-insulin resistance in PCOS patients (P<0.05 for all). There was no independent association between maternal history and the clinical or biochemical phenotype of PCOS. Conclusions PCOS patients with a positive paternal history of both DM and HT have an adverse endocrine and metabolic profile. A paternal history of DM and HT poses a risk to PCOS.

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Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome

Cited by 91 publications

References 49 publications

Metabolic Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

Metabolic Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

Reproduction and Metabolism: Insights from Polycystic Ovary Syndrome

Paternal history of diabetes mellitus and hypertension affects the prevalence and phenotype of PCOS

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