Gremlin‐1 is associated with obesity but not polycystic ovary syndrome: Insights from a body mass index‐matched analysis of bone morphogenetic protein pathway components, a cross‐sectional study

Abstract Objective This study investigates serum levels of Gremlin‐1, BMP‐4, and BMP‐7 in women with polycystic ovary syndrome (PCOS) and healthy controls and assesses their associations with body mass index (BMI) and with each other across different analytical models. Methods This cross‐sectional study included women with PCOS and BMI‐matched healthy controls, stratified into four analytical models: (Model 1) PCOS versus controls (all BMI categories combined); (Model 2) normal‐weight versus overweight/obese participants (PCOS and controls combined); (Model 3) normal‐weight, overweight, and obese participants (three‐group comparison); and (Model 4) normal‐weight PCOS, overweight/obese PCOS, normal‐weight controls, and overweight/obese controls (four‐group comparison). Demographic, anthropometric, and biochemical data were recorded. Serum BMP‐4, BMP‐7, and Gremlin‐1 levels were measured using ELISA. Group comparisons were performed using appropriate parametric or non‐parametric tests with age adjustment. Correlations between BMP‐4 and Gremlin‐1 were assessed using Spearman's rho. Results BMP‐7 concentrations were below the detection limit in most participants and quantifiable in only five cases. No significant correlation was found between BMP‐4 and Gremlin‐1 in any model. Gremlin‐1 levels were significantly higher in overweight/obese participants compared with normal‐weight individuals, independent of PCOS status (Models 2 and 4). BMP‐4 levels were higher in normal‐weight healthy controls compared with BMI‐matched normal‐weight PCOS participants ( P = 0.014; Model 4). Conclusion Gremlin‐1 levels are associated with obesity but not with PCOS, while BMP‐4 levels differ between normal‐weight PCOS and BMI‐matched controls. These findings provide new insights into BMP pathway components in PCOS and underscore the need for larger, phenotype‐stratified studies incorporating tissue‐level analyses and additional BMP antagonists.