Single-Nucleotide Polymorphism on Exon 17 of Insulin Receptor Gene Influences Insulin Resistance in PCOS: A Pilot Study on North Indian Women

Abstract

Polycystic ovarian syndrome (PCOS), a major cause of infertility, is also strongly associated with insulin resistance. Defects in insulin receptor signaling are considered as one of the major molecular pathogeneses for insulin resistance. To investigate the possible mechanism of this signaling defect at genetic level, single-nucleotide polymorphism (SNP) [His 1085 C/T] at the exon 17 of insulin receptor gene (INSR) was studied in this pilot study. Polymerase chain reaction was performed on leucocytic DNA of women diagnosed with PCOS, selected from the outpatient department of Safdarjung Hospital, New Delhi, using suitable primer to amplify a region on INSR. An equal number of age-matched healthy women were selected as controls. SNP analysis was performed with restriction enzyme length polymorphism technique using Pm II enzyme. Serum insulin level was measured by ELISA kit and HOMA-IR was calculated mathematically. A higher frequency of the CC genotype was observed in PCOS women than in controls. Also, HOMA-IR, a tool for estimating insulin resistance, was significantly high in PCOS women with the CC genotype. C1008T SNP at exon 17 of INSR is associated with insulin resistance in Indian women with PCOS. Presence of CC genotype (C1085T) could be developed as a marker for insulin resistance and metabolic complications in PCOS women.

Identification of selected genetic polymorphisms in polycystic ovary syndrome in Sri Lankan women using low cost genotyping techniques

“…On the other hand, an Indian study showed polymorphism of INSR gene as a susceptibility factor in patients with PCOS, especially in non-obese PCOS patients [24]. Yet, another Indian study reported the INSR gene SNP (rs1799817) was associated with increased insulin resistance in Indian women with PCOS [25]. However, we did not find any relationship between clinical and biochemical characteristics and the INSR gene polymorphism (rs1799817) among women with PCOS (p>0.05).…”

“…The following HPG genes and their respective SNPs were selected: GnRH1 (rs6185), FSHB (rs6169), FSHR (rs616/rs6166), LHB (rs1800447/rs34349826) and LHCGR (rs2293275). Insulin resistance playing a central role in its pathophysiology with obesity and type 2 diabetes mellitus being common problems of PCOS [22], we also selected polymorphisms in the obesity associated gene (FTO—rs9939609) and Insulin receptor gene (INSR—rs1799817) that are reported to be more prevalent in Asians [23–25].…”

Identification of Polycystic Ovary Syndrome (PCOS) Specific Genes in Cumulus and Mural Granulosa Cells

“…Concordant with the literature, many of the PCOS-specific DEGs obtained from our meta-analysis were enriched in insulin and glucose-related pathways like Type 1 and 2 diabetes mellitus, and insulin signaling pathways. Until now, studies have mostly focused on one of the common key players in these pathways, INSR and related INSR-specific SNPs, and dysregulation in the expression of this gene in PCOS [35,36]. Additionally, Purcell et al .…”

Association between insulin receptor gene exon 17 rs1799817 variant and risk of nonalcoholic fatty liver disease

“…Third, is that we did not have data on serum levels of insulin and insulin resistance which could modify the effects observed here. Given the fact that we made a comparison between the cases with NAFLD and controls with BMI<25, the lower prevalence of the "T" allele in the cases could suggest this allele either may reduce the risk of developing NAFLD per se or decrease the risk of insulin resistanceas it has been reported in a study by Gangopadhyay et al (2016). In contrast, however, in another study by Mukherjee et al (2009), "T" allele was a risk factor for insulin resistance.…”

“…Any defects in function of INSR protein might impair the biological response to insulin and lead to insulin resistance and obesity which are involved in the etiology of NAFLD (Fabbrini et al, 2010;Marchesini et al, 2001;Eguchi et al, 2006). Interestingly, in a very recently study by Gangopadhyay et al (2016), insulin resistance was significantly higher in the subjects with the rs1799817 'CC' genotype. Accordingly, our finding that the INSR rs1799817 "TT" genotype appeared to be a marker of decreased NAFLD susceptibility is consistent with the notions above.…”