Investigating oxidized LDL receptor 1 (OLR1) polymorphisms as putative genetic markers for polycystic ovary syndrome

Abstract

Polycystic ovary syndrome has a perplexing pathophysiology driven by genetic and environmental stimuli wherein the propensity for gynaecological and cardiometabolic complications is well recognized. Oxidized low density lipoprotein is a vital player in inducing endothelial dysfunction and downstream atherosclerotic processes by binding to its receptor oxidized LDL receptor 1 (OLR1). We have undertaken this case-control study to investigate whether common polymorphisms of OLR1 (K167N and 3’UTR C188T) contribute to risk of PCOS development and its related traits. Genotyping of K167N and 3’UTR C188T polymorphisms of OLR1 by direct sequencing and restriction fragment length polymorphism techniques using RsaI, respectively was carried out in 298 women with PCOS and 147 controls. Genotype and genotype-phenotype analysis was performed using additive model with appropriate statistical tests. There were no significant differences in genotypic frequency distributions between PCOS women and controls. However, K167N polymorphism showed significant association with decreased insulin levels and homeostasis model assessment of insulin resistance and increased quantitative insulin sensitivity check index, thereby ameliorating insulin resistance in women with PCOS. Contrastingly, this variant was significantly associated with increased waist-hip ratio, fasting glucose levels coupled with diminished LH levels and LH:FSH ratio in controls. The C188T polymorphism showed significant association with increased LDL only in women with PCOS. Therefore, although we did not detect significant associations of either polymorphism with PCOS susceptibility, our genotype-phenotype analysis showed that they differentially influenced metabolic traits of insulin resistance and dyslipidemia, and gonadotropin-related parameters in controls and women with PCOS. To the best of our knowledge, ours is the first study to highlight that OLR1 could be an important predisposing genetic factor for PCOS-related traits.