# ADIPOQ Variants rs1501299 and rs3774261 and Hypoadiponectinemia in Obese Women with PCOS: Genetic and Metabolic Interactions

## TL;DR

This study finds that two ADIPOQ gene variants are linked to obesity in women with PCOS, and combining genetic and metabolic data improves risk prediction.

## Contribution

The study identifies novel associations between ADIPOQ variants and obesity in PCOS and demonstrates improved risk stratification using genetic and metabolic markers.

## Key findings

- ADIPOQ variants rs1501299 and rs3774261 are significantly associated with obesity in PCOS under recessive models.
- A combined model with adiponectin, genetic variants, and PRS improves obesity risk prediction in PCOS.
- Reduced adiponectin levels are specifically linked to genotype-obesity relationships in PCOS.

## Abstract

Background: Hypoadiponectinemia, a metabolic hallmark of obesity, is common in polycystic ovary syndrome (PCOS) yet the association of variants in the ADIPOQ gene with obesity in PCOS remains uncertain. To investigate whether ADIPOQ variants are associated with obesity in PCOS in relation to circulating adiponectin levels, and whether integrating genotypes, adiponectin, and a polygenic risk score (PRS) improves risk stratification. Methodology: In 324 Tunisian women with PCOS, classified as obese or non-obese by WHO criteria, serum adiponectin was measured, and nine ADIPOQ variants were genotyped using TaqMan assays. Associations with obesity were assessed using logistic regression, gene phenotype interaction analysis, and models incorporating a PRS; epistasis, QTL, and diplotypes were also evaluated. Results: Adiponectin levels were significantly lower in obese women and modestly predicted obesity (AUC = 0.605). Variants rs1501299 and rs3774261 were significantly associated with obesity under recessive models (OR up to 5.18, 95% CI [2.32–11.56], p = 7.14 × 10−5). Risk genotypes and haplotypes correlated with reduced adiponectin and increased obesity risk, with adiponectin levels significantly associated with the genotype–obesity relationships. A combined model including adiponectin, the two variants, and PRS outperformed single predictors. Conclusions:
ADIPOQ rs1501299 and rs3774261 are associated with obesity in women with PCOS, with this association demonstrating a specific relationship with reduced adiponectin. Integrating genetic and biochemical markers improves metabolic risk profiling and supports personalized management.