Association of the Polycystic Ovary Syndrome with Genomic Variants Related to Insulin Resistance, Type 2 Diabetes Mellitus, and Obesity

• Published in: The journal of clinical endocrinology and metabolism 2004-06, Vol.89 (6), p.2640-2646
• Main Authors: San Millán, José L., Cortón, Marta, Villuendas, Gemma, Sancho, José, Peral, Belén, Escobar-Morreale, Héctor F.
• Format: Article
• Language: English
• Subjects: Adiponectin; Adolescent; Adult; Aryldialkylphosphatase - genetics; Diabetes Mellitus - epidemiology; Diabetes Mellitus - genetics; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Female; Genetic Predisposition to Disease; Genotype; Humans; Insulin Resistance - genetics; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor II - genetics; Intercellular Signaling Peptides and Proteins; Microfilament Proteins - genetics; Middle Aged; Obesity; Phosphoric Diester Hydrolases - genetics; Plasminogen Activator Inhibitor 1 - genetics; Polycystic Ovary Syndrome - epidemiology; Polycystic Ovary Syndrome - genetics; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases - genetics; Proteins - genetics; Pyrophosphatases - genetics; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 2 - genetics; Receptors, Cytoplasmic and Nuclear - genetics; Risk Factors; Transcription Factors - genetics
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-031252

We have evaluated the possible association of polycystic ovary syndrome (PCOS) with 15 genomic variants previously described to influence insulin resistance, obesity, and/or type 2 diabetes mellitus. Seventy-two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase (three variants), plasma cell differentiation antigen glycoprotein, human sorbin and SH3 domain containing 1, plasminogen activator inhibitor-1, peroxisome proliferator-activated receptor-γ2, protein tyrosine phosphatase 1B (two variants), adiponectin (two variants), IGF1, IGF2, IGF1 receptor, and IGF2 receptor. Compared with controls, PCOS patients were more frequently homozygous for the –108T variant in paraoxonase (36.6% vs. 9.5%; P = 0.002) and homozygous for G alleles of the ApaI variant in IGF2 (62.9% vs. 38.1%; P = 0.018). Paraoxonase is a serum antioxidant enzyme and, because –108T alleles result in decreased paraoxonase expression, this increase in oxidative stress might result in insulin resistance. G alleles of the ApaI variant in IGF2 may increase IGF2 expression, and IGF2 stimulates adrenal and ovarian androgen secretion. In conclusion, the paraoxonase –108 C→T variant and the ApaI polymorphism in the IGF2 gene are associated with PCOS and might contribute to increased oxidative stress, insulin resistance, and hyperandrogenism in this prevalent disorder.