Novel linkage and association of TCF7L2 variants with PCOS in Italian families

OBJECTIVE: Transcription factor 7-like 2 (TCF7L2) gene variants confer risk for type 2 diabetes and metabolic traits. We investigated the role of TCF7L2-variants in polycystic ovarian syndrome (PCOS), which is a common endocrine metabolic disorder affecting women of reproductive age. We tested whether TCF7L2 variants are in linkage to and/or in linkage disequilibrium [(LD), namely linkage and association)] with PCOS. PATIENTS AND METHODS: Within 212 families from the Italian peninsular population, we analyzed 78 variants using Pseudomarker software for linkage to and LD with PCOS under the dominant model with complete penetrance (D1). In a secondary analysis, we tested the variants under the recessive models with complete penetrance (R1), dominant with incomplete penetrance (D2), and recessive with incomplete penetrance (R2). We tested through in silico analysis the risk variants to detect any potential functional effects. RESULTS: We identified a total of 14 variants in the TCF7L2 gene significantly linked to and/or in LD with the risk of PCOS (p < 0.05) across different models. CONCLUSIONS: This study is the first to report TCF7L2 linkage and linkage disequilibrium in Italian families with PCOS.