Rs1799817 in INSR associates with susceptibility to polycystic ovary syndrome

Abstract

Summary Background Insulin and its receptor (INSR) have been implicated in the etiology of the polycystic ovarian syndrome (PCOS). Here, we investigate the association between INSR rs1799817 polymorphism and PCOS in Saudi Arabian women. Methods study group included 126 PCOS women and 118 normo-ovulatory matched controls. The demographic data was recorded, and the plasma levels of glucose, lipids, leptin, E2, LH, FSH, T, SHBG, and insulin were determined. The genotypic and allele frequencies of rs1799817 were evaluated in both PCOS and control group. Polymerase chain reaction (PCR) was used to amplify Exon 17 of the INSR gene, and the amplified products were analyzed by direct sequencing. A single-nucleotide polymorphism (C to T) was found at locus 10923 (His1058) of rs1799817. Results In the PCOS group, the mutant allele T occurs at a significantly higher frequency (0.306) compared to the control group (0.174) (p<0.001). It shows a dominant effect and elevates the relative risk of PCOS even in the heterozygotes (RR=2.82). After stratification of the participants by body mass index, the frequency of T allele was significantly higher in the lean patients with PCOS compared to the lean control. The obese PCOS also had a higher frequency than the obese control, but the difference was not statistically significant. Several parameter values were affected by the INSR genotype, particularly W/H ratio, lipid, insulin and glucose levels and insulin resistance in PCOS patients. Conclusion The INSR gene polymorphism rs1799817 is a susceptibility locus associated with PCOS in Saudis and associated metabolic and hormonal changes, particularly, in the lean PCOS females.

Nesfatin-1, Dopamine, and NADPH levels in Infertile Women with Polycystic Ovary Syndrome: Is There a Relationship Between Their Levels and Metabolic and Hormonal Variables

“…Till now, PCOS pathophysiology is unclear. Specific genetic patterns that affect the formation, regulation, and actions of sex hormones and insulin receptors seem to contribute to disease progression ( 2 ).…”

Chronic Inflammation in PCOS: The Potential Benefits of Specialized Pro-Resolving Lipid Mediators (SPMs) in the Improvement of the Resolutive Response

“…The etiology of the syndrome has not been clarified completely yet. Certain genetic patterns that impact for example synthesis, regulation and action of sex hormones and the insulin receptor, but also gestational factors like high maternal levels of androgens or AMH (anti-Müllerian hormone) seem to contribute to the onset of the disease [ 4 , 5 , 6 ]. Postnatal lifestyle factors like inadequate nutrition accompanied by a lack of physical exercise promote the development of the disease as they often result in obesity and disturbances of the glucose metabolism.…”

Transcriptomic analysis of differentially expressed genes between uterus and ovary in Xiangxi cattle

“…It has been reported previously that DNA methylation do not participate in pre-ovulatory down-regulation of HSD3B1, CYP19A1 and CYP11A1 in the follicle of bovine but it could significantly play role in permanent silencing of gene CYP19A1 in the large granuloosa lutein cells . Previously insulin and INSR have been linked in the etiology of the (PCOS) polycystic ovarian syndrome (Daghestani, 2020). However, DNA methylation analysis demonstrated that methylation of the gene of the INSR gene was linked with insulin resistance of PCOS (Zhong et al, 2021).…”