I'm going to be talking about the association of polycystic ovarian syndrome candidate gene variants with cardiovascular disease. So I have no conflict of interests. This is the outline of my presentation today, so I'll be talking about the background objectives of our study, the materials and methods, the results, the conclusion, and an acknowledgement to our team. So polycystic ovarian syndrome is the commonest endocrine disorder of women in reproductive age, and it's affecting 15% of women worldwide, which is quite a significant number. Globally, the prevalence, which has been published, ranges between 2.2% to 26%, and in Oman we conducted a study that was published when our prevalence was found to be about 7%. So the importance of polycystic ovarian syndrome is that it has reproductive and metabolic consequences to these women, and it's important to highlight that the PCOS should be diagnosed using the revised consensus of Rotterdam criteria, which are now updated to be evidence-based criteria. And I urge you all to read the international evidence-based guidelines for the assessment and management of polycystic ovarian syndrome that were published in 2023 by most of the societies around the world. There is also a complex genetic etiology to polycystic ovarian syndrome, and there are several candidate genes that have been identified by genome-wide association studies from mainly Chinese and European populations. So PCOS is associated with metabolic disorders like metabolic syndrome and diabetes that are predisposing factors for cardiovascular disease, and this has been found through meta-analysis research from women who suffer from PCOS, and they are associated with considerably higher risk of cardiovascular disease like myocardial infarction, ischemic heart disease, stroke, and they're at increased risk of mortality as well. It's also been discovered that diabetic patients with PCOS have three genes that are associated with increased vulnerability to cardiovascular disease, HLA-DRP1, LRP1, and MMP. And you can see that in this table here we have some of the genes which have been classified according to their endocrine or metabolic functions and consequences to these women with PCOS. So the objective or aim of our study is to investigate the association of three genes, LEPR, FSHR, and YALP1 variants with metabolic disorders and cardiovascular disease in women with PCOS of Arab ethnicity from Oman. So it was a prospective case-controlled study, and we had a sample size calculation. The inclusion criteria for PCOS women were according to the Rotterdam criteria. The exclusion were for women who were not Omani or not in reproductive age, pregnant women, menopausal women, those diagnosed with genetic disorders or other endocrine disorders such as hyperprolactinemia, androgen-producing tumors, congenital adrenal hyperplasia, Cushing's, and other endocrine metabolic disorders. So we recruited 50 PCO women and 50 controls for this study from Oman. We had an ethical approval, and we had internal grant from the university for the conduction of the study. And the data was collected from the electronic records. So we looked at clinical and biochemical data. For the statistical analysis, we used SPSS to do the analysis. And for the three SNPs of LEPR, FSHR, and YALP1, we looked for the association with the cardiovascular disease causation. And this is our DNA extraction methods that was utilized for the study. So going to the results. So looking at the metabolic disorders among the participants, cases, and controls. So we can find here that women with PCOS had significantly higher diabetes with an odds ratio of about 4, dyslipidemia with an odds ratio of 3, and hyperandrogenism with odds ratio of 2.6, elevated FSH to LH ratio with an odds ratio of 3, although this is not a diagnostic criteria, and anti-mullerian hormone odds ratio of 4.7. And with the new guidelines, one of the definitions that were changed was the finding of a raised AMH as an alternative to PCO ovaries on ultrasound. With regards to association of metabolic disorders and hypertension in women with polycystic ovary syndrome, we had interesting finding of these women being more likely to be hypertensive if they had metabolic syndrome with an odds ratio of 3.8. However, the contribution of all the other metabolic disorders and development of hypertension were not significant. So diabetes, dyslipidemia. We also calculated the HOMA-IR for insulin resistance, hypothyroidism, hyperandrogenism, presence of fatty liver, and anti-mullerian hormone. So for the association between the selected genes and cardiovascular disease, we had in fact looked at 11 genes, but out of these 11 genes, only the three here, which showed some association with cardiovascular disease in cases. So with LEPR, this particular variant of the gene had a B2 of 21.8, and what we did was we used a logistic binary regression to find this sort of association. The B2 values for the selected SNPs, the LEPR and the YAP1 were 21.8 compared to the FSHR, which is only 0.2. The higher the B2 value, the greater the association with the causative disease, so the higher the chance of having cardiovascular disease in patients with these particular variants. Now looking at the association between the selected genes and hypertension, the association between genes of PCOS, there were 94.9% of patients who had the homogeneous type of the gene, so the CC in the LEPR gene. The rest had the heterogeneous genotype, and for the FSHR gene, most of the patients had the heterogeneous genotype. The YAP1 shows more prevalent cases in the homozygous genotype. However, none of these genes showed any statistical significance. Association between PCOS phenotypes and cardiovascular disease and clinical findings. So this is interesting because as clinicians, it's important for us to try to identify the risk from clinical features. So just to remind you, so the phenotypes for PCOS are four, and these are according to the Rotterdam criteria for PCOM morphology. So phenotype A has hyperandrogenism, oligomenorrhea, and polycystic ovaries on ultrasound. Phenotype B is hyperandrogenism and oligomenorrhea. Phenotype C is hyperandrogenism and polycystic ovaries on ultrasound, and phenotype D is oligomenorrhea with polycystic ovaries on ultrasound. What we found was, interestingly, phenotype A females, so 43.5% of females with phenotype A tend to be hypertensive compared to 31.3% in phenotype D, so prevalent in that phenotype as well, and less prevalent in phenotype C with only 10%. And we didn't have any patients with the phenotype B in our population. So the results to the characteristics of PCO patients with a specific gene. So for LEPR, this particular variant, the mean of the dominant homozygous and mean of the heterozygous recessive genotypes, none of the parameters showed any statistical significance difference between the two groups. For the FSHR variant, the difference in the mean dominant homozygous and the heterozygous recessive genotypes, also there was no statistical significant difference between the groups. And the same for the YAP1. We did not find any difference between the homozygous and heterozygous types. So in conclusion, LEPR, this particular variant, the RS-277-9194 and the YAP1 variant were strongly linked with cardiovascular disease in PCOS cases, indicating a higher likelihood of developing cardiovascular disease. PCOS was the most prevalent cardiovascular disease. PCOS females with metabolic syndrome are 3.8 times more likely to be hypertensive. And PCOS females with a metabolic syndrome phenotype A and D are more likely to be hypertensive. And to end, I'd like to thank our research team, our medical students who was on the team who did great work, and our two doctors in epidemiology statistics and biochemistry who assisted in this research. Thank you very much.

PCOS

cardiovascular disease

gene variants

metabolic disorders

Omani women