AUTHOR=Jiao Xianting , Chen Weiwei , Zhang Jun , Wang Weiye , Song Junjiao , Chen Dan , Zhu Wenting , Shi Yuhua , Yu Xiaodan 

TITLE=Variant Alleles of the ESR1, PPARG, HMGA2, and MTHFR Genes Are Associated With Polycystic Ovary Syndrome Risk in a Chinese Population: A Case-Control Study

JOURNAL=Frontiers in Endocrinology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00504

DOI=10.3389/fendo.2018.00504

ISSN=1664-2392

ABSTRACT=<p>Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, with a prevalence of 6–8%. Although the etiology of PCOS has been investigated extensively, the association between genetic predisposition and PCOS risk is largely unknown. In this study, we genotyped 63 SNPs in 10 genes among 361 PCOS patients and 331 healthy controls in a Chinese Han population. The following variant alleles were significantly associated with decreased PCOS risk: <italic>ESR1</italic> rs9340799 (<italic>P</italic> = 0.000), <italic>PPARG</italic> rs709154 (<italic>P</italic> = 0.013), and rs1151996 (<italic>P</italic> = 0.013), <italic>HMGA2</italic> rs2272046 (<italic>P</italic> = 0.000), <italic>MTHFR</italic> rs1801133 (<italic>P</italic> = 0.000). Accordingly, the following genotypes at various loci were associated with reduced PCOS risk: GA genotype at rs9340799 (<italic>P</italic> &lt; 0.0001) in <italic>ESR1</italic>, TA genotype at rs709154(<italic>P</italic> &lt; 0.0001) in <italic>PPARG</italic> and CA genotype at rs2272046 (<italic>P</italic> &lt; 0.0001) in <italic>HMGA2</italic>. Moreover, GA genotype at rs1999805 (<italic>P</italic> = 0.013) in <italic>ESR1</italic> and TT genotype at rs1801133 in <italic>MTHFR</italic> (<italic>P</italic> &lt; 0.0001) correlated with elevated PCOS risk. Furthermore, haplotype analysis revealed significant differences in haplotype distributions of <italic>CYP11A1, ESR2</italic> and <italic>PPARG</italic> gene between cases and controls. In addition to confirming that <italic>ESR1</italic> rs9340799, <italic>HMGA2</italic> rs2272046 and <italic>MTHFR</italic> rs1801133 are related to the risk of PCOS, these findings also provide the first evidence that <italic>PPARG</italic> rs709154 and <italic>ESR1</italic> rs1999805 are significantly associated with PCOS risk in a Chinese population. Further functional studies are warranted to elucidate the underlying biological mechanisms.</p>