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

Abu-Hijleh, Tala M.; Gammoh, Emily; Al-Busaidi, Amna S; Malalla, Zainab H.; Madan, Samira; Mahmood, Naeema; Almawi, Wassim Y.

doi:10.1159/000441570

Cited by 28 publications

(21 citation statements)

References 44 publications

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“…Family-based and case-control association studies have found that rs1799941 and rs727428 in SHBG gene influenced SHBG metabolism in American and Mediterranean women with PCOS [ 133 , 134 ], but not PCOS risk [ 133 ]. A recent study in Bahraini women has concluded that haplotypes spanning six polymorphisms were associated with either increased or decreased PCOS susceptibility [ 135 ] rekindling interest in SHBG gene polymorphisms in PCOS susceptibility.…”

Section: Genetics Of Pcosmentioning

confidence: 99%

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Dadachanji

Shaikh

Mukherjee

2018

Genetics Research International

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Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits.

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Section: Genetics Of Pcosmentioning

confidence: 99%

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Dadachanji

Shaikh

Mukherjee

2018

Genetics Research International

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“…Primers shown in Table 1 were synthesized by Nanjing Lejin Biotechnology Co, Ltd (Nanjing, China), 17 and the PCR kit used in the study was purchased from Nanjing Jian Cheng Biotechnology Co, Ltd. A total of 20 μL reaction system was as follows: 1 μL DNA, 1 μL forward primer (10 pmol/mL), 1 μL reverse primer (10 pmol/mL), 10 μL PCR mixture, and 7 μL deionized water. The reaction conditions were as follows: predenaturation at 95°C for 5 minutes; and 35 cycles of denaturation at 95°C for 30 seconds, annealing at 62°C for 40 seconds, and extension at 72°C for 45 seconds, with final extension at 72°C for 10 minutes.…”

Section: Polymerase Chain Reaction-restriction Fragment Length Polymorphismmentioning

confidence: 99%

Effect of sex hormone–binding globulin polymorphisms on the outcome of in vitro fertilization‐embryo transfer for polycystic ovary syndrome patients: A case‐control study

Liu

Zhao

et al. 2018

J of Cellular Biochemistry

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Polycystic ovary syndrome (PCOS), known as a common endocrine disorder among females, plagues many PCOS patients. The current study aimed to explore the correlations of sex hormone-binding globulin (SHBG) polymorphisms with the outcome of in vitro fertilization-embryo transfer (IVF-ET) in PCOS patients. PCOS patients who underwent IVF-ET and patients with non-PCOS-related infertility were selected in the study. Correlations of SHBG rs6259 and rs727428 with the risk factors in PCOS were analyzed, followed by the evaluation of the effect of SHBG polymorphisms on the outcome of IVF-ET in PCOS patients. At last, unconditional logistic regression analysis was performed to study the risk factors for IVF-ET treatment outcome. Compared with SHBG rs6259 GG carriers, the incidence of PCOS was found to be elevated in SHBG rs6259 GA+AA carriers which indicated that the A allele was a risk factor for PCOS. Compared with SHBG rs6259 TT carriers, the number of retrieved oocytes and embryo as well as the fertility rate in SHBG rs6259 GA+AA carriers was found to be decreased, while the abortion rate, incidence of ovarian hyperstimulation syndrome, transplant rejection rate, estradiol, and testosterone in serum, as well as testosterone in follicular fluid were elevated. The luteal hormone, serum testosterone, and progesterone and GA+AA genotype of rs6259 were the risk factors for IVF-ET treatment outcome. Taken together, the study showed that SHBG rs6259 polymorphisms might be correlated with the risk of PCOS and the outcome of IVF-ET treatment.

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“…On the other hand, E326K, another missense polymorphism on exon eight, lowers SHBG levels and influences the SHBG metabolism independent of BMI, androgen, and insulin-related traits in PCOS women [ 69 ]. A recent study conducted in Bahraini women reported that specific SHBG variants affecting the SHBG concentrations and SHBG haplotypes spanning six polymorphisms were linked to increased or decreased PCOS susceptibility [ 183 ]. Thus, SHBG can be considered as a candidate gene playing a central role in the pathophysiology of PCOS.…”

Section: Shbgmentioning

confidence: 99%

The role of polymorphism in various potential genes on polycystic ovary syndrome susceptibility and pathogenesis

et al. 2021

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Polycystic ovary syndrome (PCOS) is the most common endocrinopathies affecting the early reproductive age in women, whose pathophysiology perplexes many researchers till today. This syndrome is classically categorized by hyperandrogenism and/or hyperandrogenemia, menstrual and ovulatory dysfunction, bulky multi follicular ovaries on Ultrasonography (USG), and metabolic abnormalities such as hyperinsulinemia, dyslipidemia, obesity. The etiopathogenesis of PCOS is not fully elucidated, but it seems that the hypothalamus-pituitary-ovarian axis, ovarian, and/or adrenal androgen secretion may contribute to developing the syndrome. Infertility and poor reproductive health in women’s lives are highly associated with elevated levels of androgens. Studies with ovarian theca cells taken from PCOS women have demonstrated increased androgen production due to augmented ovarian steroidogenesis attributed to mainly altered expression of critical enzymes (Cytochrome P450 enzymes: CYP17, CYP21, CYP19, CYP11A) in the steroid hormone biosynthesis pathway. Despite the heterogeneity of PCOS, candidate gene studies are the widely used technique to delineate the genetic variants and analyze for the correlation of androgen biosynthesis pathway and those affecting the secretion or action of insulin with PCOS etiology. Linkage and association studies have predicted the relationship between genetic variants and PCOS risk among families or populations. Several genes have been proposed as playing a role in the etiopathogenesis of PCOS, and the presence of mutations and/or polymorphisms has been discovered, which suggests that PCOS has a vital heritable component. The following review summarizes the influence of polymorphisms in crucial genes of the steroidogenesis pathway leading to intraovarian hyperandrogenism which can result in PCOS.

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

Cited by 28 publications

References 44 publications

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Effect of sex hormone–binding globulin polymorphisms on the outcome of in vitro fertilization‐embryo transfer for polycystic ovary syndrome patients: A case‐control study

The role of polymorphism in various potential genes on polycystic ovary syndrome susceptibility and pathogenesis

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