Role of D327N sex hormone-binding globulin gene polymorphism in the pathogenesis of polycystic ovary syndrome

Bendlová, Běla; Zavadilová, Jana; Vaňková, Markéta; Vejražková, Daniela; Lukasova, Petra; Včelák, Josef; Hill, Martin; Cibula, David; Vondra, K; Stárka, L.; Vrbíková, Jana

doi:10.1016/j.jsbmb.2006.10.002

Cited by 21 publications

(21 citation statements)

References 52 publications

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“…In contrast, rs858521 was negatively associated with PCOS, thus assigning a protective nature to this SNP. In our hands, rs6259 was not linked with altered PCOS risk, in agreement with the study of Bendlová et al [39] , but in contrast to a study on Mediterranean women, which showed that carriage of rs6259 minor allele was associated with re- duced risk of PCOS [16] . This discrepancy could be explained by a difference in the racial/ethnic background and in selection of study subjects.…”

Section: Discussionsupporting

confidence: 93%

“…Neither rs6257 nor rs6259 were significantly associated with altered SHBG levels or PCOS, in agreement with the studies by Wickham et al [20] and Bendlová et al [39] , but in disagreement with the study by Ding et al [29] , which reported on significantly higher and lower SHBG levels in postmenopausal women associated with rs6259 and rs6257, respectively. Furthermore, it was reported that rs6257 (and rs1799941), but not rs6259, was associated with altered SHBG levels in age-and weightadjusted analysis of postmenopausal women [21] .…”

Section: Discussionsupporting

confidence: 72%

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Common Variants in the Sex Hormone-Binding Globulin (SHBG) Gene Influence SHBG Levels in Women with Polycystic Ovary Syndrome

Abu-Hijleh

Gammoh²,

Al-Busaidi³

et al. 2015

Ann Nutr Metab

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Background: Decreased sex hormone-binding globulin (SHBG) levels were associated with polycystic ovary syndrome (PCOS). SHBG polymorphisms associated with reduced SHBG production were tested for their association with PCOS, but with inconclusive results. We tested whether altered SHBG levels and SHBG variants were associated with PCOS. Methods: The study subjects included 242 women with PCOS and 238 control women. SHBG genotyping was done by real-time PCR. Results: Higher minor allele frequency of rs13894, rs858521 and rs727428 was seen in PCOS cases, and significant differences in rs858521 and rs727428 genotypes distribution were seen between PCOS cases and controls. Multivariate regression analysis confirmed the association of only rs727428 with PCOS. Though it was not statistically significant, serum SHBG levels were reduced according to rs727428 genotypes in PCOS cases than in controls. Carriage of rs727428 minor allele was associated with significant increases in free/bioactive testosterone in PCOS cases. Seven-locus (rs9898876-rs13894-rs858521-rs1799941-rs6257-rs6259-rs727428) haploview analysis showed increased frequency of GCCGTGA, GTCGTGA and GTCATGG, and reduced frequency of GTCGTGG haplotypes in PCOS cases than in controls, thus conferring disease susceptibility and protective nature to these haplotypes, respectively. Conclusion: Specific SHBG variants affecting serum SHBG levels and SHBG haplotypes are associated with PCOS, suggesting the role for SHBG as PCOS candidate gene.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 72%

Common Variants in the Sex Hormone-Binding Globulin (SHBG) Gene Influence SHBG Levels in Women with Polycystic Ovary Syndrome

Abu-Hijleh

Gammoh²,

Al-Busaidi³

et al. 2015

Ann Nutr Metab

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“…The p.D327N polymorphism in this gene was not found to influence PCOS susceptibility in studies in Slovenia or the Czech Republic (Bendlova et al ., 2007; Ferk et al ., 2007). …”

Section: Resultsmentioning

confidence: 99%

Functional genetic polymorphisms and female reproductive disorders: Part I: polycystic ovary syndrome and ovarian response

Simoni

Tempfer

Destenaves

et al. 2008

Human Reproduction Update

124

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BACKGROUNDThe identification of polymorphisms associated with a disease can help to elucidate its pathogenesis, and this knowledge can be used to improve prognosis for women with a particular disorder, such as polycystic ovary syndrome (PCOS). Since an altered response to ovarian stimulation is also a characteristic of the disease, further knowledge about its aetiology could help in defining the parameters that determine the response of an individual to ovarian stimulation.METHODSPubMed and EMBASE databases were systematically searched for gene association studies published until the end of August 2007, using search criteria relevant to PCOS and ovarian response to stimulation. Data from additional papers identified through hand searches were also included; 139 publications were reviewed.RESULTSSeveral genes involved in ovarian function and metabolism are associated with increased susceptibility to PCOS, but none is strong enough to correlate alone with susceptibility to the disease, or response to therapy. A single-nucleotide polymorphism in exon 10 of the FSH receptor (FSHR) gene, FSHR p.N680S, was consistently identified as having a significant association with ovarian response to FSH.CONCLUSIONSNo consistent association between gene polymorphism and PCOS could be identified. The FSHR gene may play a significant role in the success of ovarian stimulation, and can be used as a marker to predict differences in FSHR function and ovarian response to FSH. Genotyping the FSHR p.N680S polymorphism may provide a means of identifying a population of poor responders before in vitro fertilization procedures are initiated.

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“…Recently, it was postulated that polymorphisms within the coding sequence and in the regulatory sequence of the SHBG gene were associated with circulating SHBG levels, which may be a possible genetic background of sex hormone activity in humans (41,42). On the other hand, Bendlova et al reported no significant differences in the genotype distribution between PCOS and controls and no association with plasma SHBG levels (43). Nevertheless, there may be a genetic determination of low SHBG levels contributing to an increase in biologically active androgen levels during fetal, pubertal, and later in life, resulting in different phenotypes of androgen excess (42).…”

Section: Discussionmentioning

confidence: 99%

Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome

Kajaia¹,

Binder²,

Dittrich³

et al. 2007

eur j endocrinol

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Background: The aim of the present study is to assess insulin resistance (IR) in women with hyperandrogenic syndrome, which was suggested to replace the term polycystic ovary syndrome by the Androgen Excess Society, and to evaluate whether sex hormone-binding globulin (SHBG) can be used as a predictive marker of IR in hyperandrogenic women. Methods: Clinical, metabolic, and endocrine parameters were measured, and an oral glucose tolerance test was carried out. The women were classified as IR group or non-IR group, in accordance with defined cutoff points for the homeostatic model assessment of IR (HOMA-IR) at R2.5, the quantitative insulin sensitivity check index at %0.33, and the Matsuda insulin sensitivity index (ISI) at %5. Results: The women classified as having IR had a significantly higher body mass index (BMI) and free androgen index (FAI) and showed significantly lower SHBG and high-density lipoprotein (HDL) levels, regardless of the indices used. However, with the Matsuda ISI, generally more women were diagnosed as having IR, and this group had significantly higher total testosterone and triglyceride values, as well as a higher incidence of hirsutism. Conclusions: Women who were classified as being insulin resistant using insulin sensitivity indices showed significantly higher BMI and FAI values and lower SHBG and HDL levels. However, the Matsuda ISI may be more favorable for identifying IR in hyperandrogenic women. SHBG may serve as a predictive marker of IR in these women, particularly in those who are obese.

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Role of D327N sex hormone-binding globulin gene polymorphism in the pathogenesis of polycystic ovary syndrome

Cited by 21 publications

References 52 publications

Common Variants in the Sex Hormone-Binding Globulin (SHBG) Gene Influence SHBG Levels in Women with Polycystic Ovary Syndrome

Common Variants in the Sex Hormone-Binding Globulin (SHBG) Gene Influence SHBG Levels in Women with Polycystic Ovary Syndrome

Functional genetic polymorphisms and female reproductive disorders: Part I: polycystic ovary syndrome and ovarian response

Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome

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