AUTHOR=Tian Ye , Li Jingyu , Su Shizhen , Cao Yongzhi , Wang Zhao , Zhao Shigang , Zhao Han 

TITLE=PCOS-GWAS Susceptibility Variants in THADA, INSR, TOX3, and DENND1A Are Associated With Metabolic Syndrome or Insulin Resistance in Women With PCOS

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00274

DOI=10.3389/fendo.2020.00274

ISSN=1664-2392

ABSTRACT=<p>Polycystic ovary syndrome is characterized by reproductive and metabolic disturbances throughout the female lifespan. Therefore, this study aimed to determine whether genome-wide association studies (GWAS)-identified risk variants for PCOS could confer risk of metabolic syndrome (MS) or insulin resistance (IR). Fifteen independent SNPs mapping to 11 GWAS loci genotyped in a total of 2,082 Han Chinese women independent of previous GWAS and phenotype-genotype correlations were assessed. The CC group for rs12478601 in <italic>THADA</italic> was associated with decreased rate of MS after adjustment for age (23.2 vs. 27%, <italic>P</italic> = 0.042, OR = 0.81). Using a dominant model, the GG+AG group for rs2059807 in <italic>INSR</italic> was associated with increased risk of MS after adjustment for age (26.8 vs. 22.5%, <italic>P</italic> = 0.023, OR = 1.27). The GG + GT group for rs4784165 in <italic>TOX3</italic> was found to be associated with an increased rate of IR after adjustment for age and BMI(53.3 vs. 48.5%, <italic>P</italic> = 0.027, OR = 1.27). The GG+AG group for rs2479106 in <italic>DENND1A</italic> was associated with a decreased rate of IR (48.3 vs. 53.6%, adjusted <italic>P</italic> = 0.039, OR = 0.80). After exclusion of PCOS cases with a family history of diabetes, hypertension, or dyslipidemia, the phenotype-genotype correlations between the genes <italic>INSR</italic> and <italic>TOX3</italic> and MS or IR were still significant (<italic>P</italic> &lt; 0.05). Three SNPs (rs13429458 in <italic>THADA</italic>, rs10818854 in <italic>DENND1A</italic>, and rs2059807 in <italic>INSR</italic>) were significantly associated with IR; however, their association was not significant after adjustment for age and BMI. This genotype-phenotype study thus provides clues that <italic>THADA, INSR, TOX3</italic>, and <italic>DENND1A</italic> play a role in PCOS possibly through a metabolic disorder-related pathway.</p>