Interplay between elevated RAB5B gene expression and insulin resistance among women with PCOS-insights from a case-control study

Background: Polycystic ovary syndrome (PCOS) represents a multifaceted endocrine, reproductive, and metabolic disorder characterized by hyperandrogenism and hyperinsulinemia-induced insulin resistance (IR). Recent studies reported that the etiology of PCOS is likely correlated with genes involved in steriodogenesis, IR and glucose metabolism. Among the candidate genes in insulin signaling pathways, RAB5B, a small GTPase involved in vesicle trafficking, significantly impacts cellular pathways in ovarian follicular cells, leading to clinical and endocrine changes among women with PCOS. Additionally, RAB5B is crucial for insulin-mediated glucose uptake and is involved in PI3K, AKT, and MAPK/ERK pathways, affecting LHCGR-stimulated steroidogenesis. Despite extensive research, the precise molecular mechanisms underlying RAB5B mediated IR in PCOS remained elusive.

Objective: The study aimed to explore the potential link between RAB5B gene expression and IR among women with PCOS.

Methodology: A total of age matched 270 subjects were enrolled in this study including 135 PCOS women and 135 apparently healthy controls. These study participants were subjected to detailed medical history, clinical and physical examination. All subjects were further evaluated for biochemical, hormonal and RAB5B gene expression estimation. Expression levels of RAB5B gene were analyzed using gene-specific primers and the SYBR® Green PCR Kit (Qiagen, Germany) and their qPCR reaction mix, according to the manufacturer's guidelines. Student t-test and ANOVA were used to evaluate the differences in the means of various parameters.

Results: The HOMA-IR (2.28 ± 1.4 vs. 1.36 ± 0.73) was significantly elevated among women with PCOS than controls (p < 0.05). We also found that the QUICKI (0.35 ± 0.04 vs. 0.37 ± 0.04), MATSUDA (12.59 ± 4.71 vs. 15.47 ± 4.33) and FGIR (11.56 ± 7.06 vs. 14.32 ± 8.66) were higher in controls than women with PCOS (p < 0.05). We also observed that women with PCOS had elevated levels of RAB5B mRNA levels when compared with apparently healthy controls. Bivariate correlation analysis among HOMA-IR stratified PCOS and control subjects revealed strong negative correlation between IR⁺ PCOS and IR^- PCOS (r = -0.61, P < 0.05) and IR^- control (r = -0.37, p < 0.05) subjects respectively.

Conclusion: Our study demonstrated that there is potential link between RAB5B gene expression and IR specifically in the context of IR indices among women with PCOS.