AKT2: First Evidence of Genetic Association with Polycystic Ovary Syndrome

Mark O. Goodarzi, MD, PhD, Michelle R. Jones, BSc, Yii-Der I. Chen, PhD and Ricardo Azziz, MD, MBA, MPH
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine (M.O.G., M.R.J.), Department of Obstetrics and Gynecology (M.O.G., Y-D.I.C., R.A.), and Medical Genetics Institute (M.O.G., Y-D.I.C.), Cedars-Sinai Medical Center, Los Angeles, California 90048; and Departments of Medicine (M.O.G., Y-D.I.C., R.A.) and Obstetrics and Gynecology (R.A.), the David Geffen School of Medicine at UCLA, Los Angeles, California 90095
Diabetes Care


Objective: Insulin resistance has been reported in up to 70% of women with polycystic ovary syndrome (PCOS). Physiologic and genetic data currently implicate post-insulin receptor signaling defects in substrates such as GSK3? . The AKT2 gene was chosen as a candidate for PCOS because its product affects glucose metabolism and mitogenic signaling, interacts with GSK3?, and mediates cell survival in the ovary.

Research Design and Methods: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. 287 White women with PCOS and 187 White controls were genotyped for 4 SNPs in AKT2. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Single nucleotide polymorphisms (SNPs) and haplotypes were tested for association with PCOS risk and phenotypic markers of PCOS.

Results: Minor allele carriers of SNPs rs3730051 and rs8100018 had increased odds of PCOS (OR=2.2, p=0.004 and OR=2.4, p=0.001, respectively). The haplotype T-G-C-T was significantly associated with PCOS (OR=2.0, p=0.01). Carriers of the risk haplotypes for both AKT2 and GSK3B had a further increased odds of PCOS (OR=3.1, p=0.005).

Conclusions: These data suggest that polymorphisms in two components of the insulin signaling pathway, AKT2 and GSK3B, are associated with PCOS. Presence of multiple lesions in a single pathway may confer increased risk.

Next Steps

Becoming victorious over the symptoms of Polycystic Ovary Syndrome is not easy, but you can overcome your PCOS symptoms to live the life you deserve.

It takes strength, courage, and perseverance. It can be challenging and that’s why Insulite Health created this website. It's has information and resources that will help you balance your hormones and reverse PCOS symptoms.

So take these next steps now! Use the links below to learn how to make the changes that will transform your health and your life forever.

  1. Read more about PCOS. Search our 1300 page PCOS library.
  2. Join our Facebook Group right now!  Pose your questions to this group of like-minded women and get the support you need.
  3. Take the PCOS Quiz! Get your PCOS score and assess your risk.  
  4. Learn more about the Insulite 5-Element PCOS Solution

Insulite Health, is committed to helping women reverse their symptoms of hormone imbalance. Scientific research has revealed that this imbalance can be a primary cause of many devastating health symptoms. Hormone Imbalance can also underlie the increased risk factors for PCOS (Polycystic Ovarian Syndrome) - a major source of serious diseases as well as cause of excess weight gain, adult acne, unwanted facial hair, depression, anxiety, and heartbreaking female infertility.

©Insulite Health, Inc., pcos.com empowers women with PCOS to transform their lives through a process of healing with the 5-Element PCOS System – a complete solution for helping women reverse the symptoms of PCOS and hormone imbalance.