Clinical Manifestations of Hyperandrogenism and Ovulatory Dysfunction Are Not Associated with His1058 C/T SNP (rs1799817) Polymorphism of Insulin Receptor Gene Tyrosine Kinase Domain in Kashmiri Women with PCOS

Rasool, Shabhat; Ashraf, Sairish; Nabi, Mudasar; Masoodi, Shariq Rashid; Fazili, Khalid Majid; Amin, Shajrul

doi:10.1155/2021/7522487

Cited by 5 publications

(5 citation statements)

References 36 publications

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“…A gene susceptibility test for PCOS may reduce the risk of obesity, cardiovascular disease, and T2DM in the long run [48]. SNPs in genes related to insulin signaling are potential candidates to explain PCOS's clinical manifestations since insulin resistance is a common finding in the disorder [14]. Even though many PCOS women are more likely to develop insulin resistance, poor glucose tolerance, and pancreatic dysfunction, which increases their risk of developing T2DM later in life, there may be fundamental differences in the mechanism of insulin resistance in T2DM and PCOS.…”

Section: Discussionmentioning

confidence: 99%

“…IGF2BP2 is encoded by the IGF2BP2 gene located on chromosome 3q27 [12,13]. PCOS is characterized by insulin resistance; therefore, SNPs linked to the insulin signaling pathways may contribute to the development of PCOS's clinical features [14]. Two SNPs, the rs11705701 G/A (GRCh38.p12, minor allele frequency [MAF] = 0.49) and rs1470579 A/C (GRCh37.p13, MAF = 0.45), have already been correlated to T2DM susceptibility in other races [15].…”

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confidence: 99%

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IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome

Govahi Kakhki,

Sargazi,

Montazerifar

et al. 2024

Clinical Laboratory Analysis

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BackgroundInsulin resistance has been correlated with the genetic diversity within the insulin‐like binding proteins genes. Moreover, insulin resistance is one of the key characteristics of the widespread reproductive endocrine condition known as polycystic ovarian syndrome (PCOS). Hence, this study is aimed to determine the association between IGFBP3 and IGF2BP2 gene variants and PCOS risk.MethodsA total of 300 subjects (150 PCOS cases diagnosed based on Rotterdam ESHRE/ASRM consensus criteria and 150 healthy subjects) were recruited in this case–control cross‐sectional study. Tetra‐primer amplification refractory mutation system polymerase chain reaction (ARMS‐PCR) was used for genotyping rs11705701, whereas genotyping of rs1470579 and rs2854744 was done employing PCR‐restriction fragment length polymorphism (PCR‐RFLP) technique.ResultsThe CC and AA+AC genotypes of rs1470579 conferred an increased risk of PCOS in our population. Regarding the rs2854744, an increased risk of PCOS was observed under the codominant homozygous (TT vs. GG) model by 2.54 fold. The C allele of rs1470579 and T allele of rs2854744 enhanced PCOS risk by 1.97 and 1.46 folds, respectively. Haplotype analysis showed that the Ars1470579Ars11705701 haplotype conferred a decreased risk of PCOS (odds ratio = 0.53, 95% confidence interval = 0.34–0.83, p = 0.006). The AC/GG/GT, AA/GA/GT, AC/GA/GG, and AC/GA/GT genotype combinations of rs1470579/rs11705701/rs2854744 were associated with a decreased risk of the disease.ConclusionsIGF2BP2 rs1470579 and IGFBP3 rs2854744 enhanced PCOS susceptibility in a Southeastern Iranian population. Further investigation involving larger cohorts representing diverse ethnic backgrounds is needed to confirm the current findings.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome

Govahi Kakhki,

Sargazi,

Montazerifar

et al. 2024

Clinical Laboratory Analysis

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“…It has been found that IRS-1 G972R polymorphism is directly associated with the insulin receptors and inhibits autophosphorylation of INSR. This association has been found to occur in the β subunit of INSR that includes the tyrosine kinase domain at residues 966 and 1271 [ 46 ]. This interaction also involves INSR His1058 residue, indicating a relationship between INSR C/T polymorphism and IRS-1 Gly972Arg polymorphism.…”

Section: Discussionmentioning

confidence: 99%

Insulin Receptor Substrate 1 Gly972Arg (rs1801278) Polymorphism Is Associated with Obesity and Insulin Resistance in Kashmiri Women with Polycystic Ovary Syndrome

Rasool

Nabi

Ashraf

et al. 2022

Genes

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Background: Polycystic ovary syndrome (PCOS) is commonly associated with metabolic abnormalities such as hyperinsulinemia, insulin resistance and obesity. The genetic variants of genes regulating insulin action, expression and regulation are suggested as possible factors involved in development and severity of clinical manifestations in PCOS. Aim: We investigated whether IRS-1Gly972Arg (rs1801278) polymorphism is associated with increased risk of PCOS in Kashmiri women. The correlation of various clinical, metabolic and hormonal markers with rs1801278 single nucleotide polymorphism was analyzed. The genotypic–phenotypic association of clinical manifestations of PCOS with the tested genetic variant was also assessed. Results: There were no significant differences in allele frequency (OR = 0.87, CI = 0.59–1.29, χ2 = 0.456, p = 0.499) or genotypic distribution (χ2 = 3.73, p = 0.15) between PCOS women and controls. No significant association was also found in the dominant (OR = 1.63, χ2 = 0.377, p = 0.53), recessive (OR = 0.79, χ2 = 1.01, p = 0.31) or heterozygote vs. homozygote (OR = 1.34, χ2 = 1.53, p = 0.22) genotype model analysis. The genotype–phenotype correlation analysis showed that the Arg allele was significantly associated with increased central adiposity markers hip circumference (p = 0.012), and body adiposity index BAI (p = 0.002) in the recessive model in PCOS women. The two-hour glucose (p = 0.04) and insulin resistance marker HOMA (p = 0.44) were significantly higher in Arg allele carriers. The androgen excess markers dehydroepiandrosterone sulfate DHEAS (p = 0.02), Ferriman–Gallwey score (p = 0.012), prevalence of acne, alopecia and hirsutism (all p < 0.01) were significantly elevated in the wild-type GG genotype. Conclusions:IRS-1Gly972Arg genetic variant does not increase the risk of PCOS in Kashmiri women. However, this polymorphism is associated with clinical manifestations of insulin resistance, obesity and hyperandrogenism, suggesting its possible role in variable phenotypic manifestations of PCOS.

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“…Significant internal factors are involved in the development of PCOS-related insulin resistance, although in some cases, it may only be acquired due to exogenous obesity. The root cause of PCOS is related to defects in intracellular insulin signaling downstream of the insulin receptor, which includes the hyperphosphorylation of serine residues on the insulin receptor substrate 1 (IRS-1) protein, which then binds to the insulin receptor and initiates insulin-specific intracellular responses (82)(83)(84). Insulin resistance has been observed not only in peripheral tissues of PCOS patients, such as adipocytes and skeletal muscle, but also in fibroblasts and ovarian granulosa and theca cells.…”

Section: Elevated Insulin Resistance In the Development Of Pcosmentioning

confidence: 99%

The role of the thyroid in polycystic ovary syndrome

Fan,

Ren,

Sheng

et al. 2023

Front. Endocrinol.

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Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease in women of childbearing age and can cause metabolic disorder, infertility, and increased anxiety and depression; as a result, it can seriously affect the physical and mental health of fertile women. PCOS is a highly clinically heterogeneous disease with unclear etiology and pathogenesis, which increases the difficulty of treatment. The thyroid gland has complex regulatory effects on metabolism, reproduction, and emotion, and produces hormones that act on almost all cells of the human body. The clinical manifestations of PCOS are similar to some thyroid diseases. Furthermore, some thyroid diseases, such as subclinical hypothyroidism (SCH), not only increase the incidence rate of PCOS, but also exacerbate its associated metabolic abnormalities and reproductive disorders. Interestingly, PCOS also increases the incidence of some thyroid diseases. However, the role of the thyroid in PCOS remains unclear. This review is intended to thoroughly explore the critical role of the thyroid in PCOS by summarizing the comorbidity of PCOS and thyroid diseases and their combined role in metabolic disorders, related metabolic diseases, and reproductive disorders; and by analyzing the potential mechanism through which the thyroid influences the development and progression of PCOS and its symptoms. We hope this review will provide a valuable reference for the role of the thyroid in PCOS.

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Clinical Manifestations of Hyperandrogenism and Ovulatory Dysfunction Are Not Associated with His1058 C/T SNP (rs1799817) Polymorphism of Insulin Receptor Gene Tyrosine Kinase Domain in Kashmiri Women with PCOS

Cited by 5 publications

References 36 publications

IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome

IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome

Insulin Receptor Substrate 1 Gly972Arg (rs1801278) Polymorphism Is Associated with Obesity and Insulin Resistance in Kashmiri Women with Polycystic Ovary Syndrome

The role of the thyroid in polycystic ovary syndrome

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