Dataset Information

Role of Single Nucleotide Variants in the YAP1 Gene in Adolescents with Polycystic Ovary Syndrome.

ABSTRACT:

Background

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women. It can manifest in adolescence, affecting up to 8% of adolescents. Long-term health consequences characteristic of PCOS are impaired fertility, increased risk of type 2 diabetes, metabolic disorders and cardiovascular disease. All of these sequelae are exacerbated by increased body weight, a major feature of PCOS. The protein encoded by the YAP1 gene plays a key role in one of the pivotal mechanisms that govern cellular/organismal metabolism and contributes to the pathogenesis of metabolic diseases.

Aim

To compare the prevalence of single nucleotide variants (SNVs) in the YAP1 gene among adolescents with PCOS, adolescents at risk of PCOS development and healthy adolescents, and assess their association with the clinical characteristics of PCOS.

Results

The frequencies of the five investigated YAP1 gene SNVs (rs11225161, rs11225166, rs3858420, rs11225138 and rs79981660) were not significantly different among adolescents with PCOS, risk group patients and healthy controls. Furthermore, none of the SNVs contributed to the clinical characteristics of adolescents with PCOS and adolescents at risk of PCOS development.

Conclusions

No significant associations were found between PCOS in adolescents and the five investigated SNVs in the YAP1 gene.

SUBMITTER: Lidaka L

PROVIDER: S-EPMC9312887 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Role of Single Nucleotide Variants in the <i>YAP1</i> Gene in Adolescents with Polycystic Ovary Syndrome.

Lidaka Lasma L Bekere Laine L Lazdane Gunta G Lazovska Marija M Dzivite-Krisane Iveta I Gailite Linda L

Biomedicines 20220713 7

<h4>Background</h4>Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women. It can manifest in adolescence, affecting up to 8% of adolescents. Long-term health consequences characteristic of PCOS are impaired fertility, increased risk of type 2 diabetes, metabolic disorders and cardiovascular disease. All of these sequelae are exacerbated by increased body weight, a major feature of PCOS. The protein encoded by the <i>YAP1</i> gene plays a key role in one of the pivo ...[more]

PMID: 35884992

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Project description:Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women, affecting up to 16.6% of reproductive-age women. PCOS symptoms in adolescents comprise oligomenorrhoea/amenorrhoea and biochemical and/or clinical hyperandrogenism. Long-term health risks of PCOS patients include infertility, metabolic syndrome, type 2 diabetes and cardiovascular disease. Genetic factors have been proven to play a role in development of the syndrome and its symptoms. To investigate single nucleotide variants (SNVs) in the GNRHR, ESR2, LHCGR and FSHR genes in adolescent patients with PCOS and their association with PCOS symptoms. We conducted a cross-sectional study comprising of 152 adolescents: 63 patients with PCOS, 22 patients at risk of developing PCOS and 67 healthy controls. Participants were recruited from out-patients attending a gynaecologist at the Children's Clinical University Hospital, Riga, Latvia, between January 2017 and December 2020. Genomic DNA was extracted from whole blood, and SNVs in the GNRHR, ESR2, LHCGR and FSHR genes were genotyped. The distributions of SNV genotypes were compared among the three groups and genotype-phenotype associations within the PCOS group were evaluated. No statistically significant differences were found in the distributions of genotypes for GNRHR (rs104893837), ESR2 (rs4986938), LHCGR (rs2293275) and FSHR (rs6166, rs6165, rs2349415) among PCOS patients, risk patients and healthy controls. Within the PCOS group, ESR2 rs4986938 minor allele homozygous patients had a significantly higher level of total testosterone than major allele homozygous patients and heterozygous patients. A significantly higher total testosterone level was also observed in PCOS patients carrying the LHCGR rs2293275 minor allele compared with major allele homozygous patients. The SNVs ESR2 rs4986938 and LHCGR rs2293275 play a role in the phenotypic characteristics of PCOS. To fully uncover their influence on the development of PCOS and its symptoms, further studies of larger cohorts and a follow up of this study sample through to adulthood are required. Furthermore, studies of adolescent PCOS patients conducted prior to the latest European Society of Human Reproduction and Embryology (ESHRE) criteria (2018) should be re-evaluated as the study groups might include risk patients according to these updated criteria, thereby potentially significantly impacting the published results.

Project description:BackgroundEtiology of polycystic ovary syndrome (PCOS) is attributed to genetic and environmental factors. One environmental factor is oxidative stress. Paraoxonase 1 (PON1) is an antioxidant high-density lipoprotein-associated enzyme encoded by the PON1 gene. The PON1 gene has been implicated in the risk for PCOS, the influence of which appears to come from single nucleotide variants (SNVs) at multiple genetic loci. However, association study reports have been inconsistent which compels a meta-analysis to obtain more precise estimates.MethodsFrom 12 publications, extracted genotype data were used in two genetic procedures. First, linkage disequilibrium (LD) was used to group eight PON SNVs into three: LD1, LD2 and LD3. Second, frequencies of the variant (var), wild-type (wt) and heterozygous (het) genotypes were used for genetic modeling (allele-genotype for LD1 and standard for LD2 and LD3). Risk associations were expressed in terms of pooled odds ratios (ORs), 95% confidence intervals (CIs) and Pa-values. Evidence was considered strong when significance was high (Pa < 0.0001) and heterogeneity absent (I2 = 0%). Pooled effects were subjected to modifier (power), subgroup (Asian/Caucasian), outlier, sensitivity and publication bias treatments. Multiple comparisons were Bonferroni-corrected.ResultsThis meta-analysis generated 11 significant outcomes, five in LD1, six in LD2 and none in LD3. All six LD2 outcomes did not survive the Bonferroni-correction but two of the five in LD1 did. These two core LD1 findings conferred greater odds of PCOS to the var allele in the highly significant (Pa < 0.0001) overall (OR 1.44, 95% CI 1.24-1.67) and Asian (OR 1.41, 95% CI 1.20-1.65) outcomes. Of these two core outcomes, the Asian effect was homogeneous (I2 = 0%) but not the overall (I2 = 29%).ConclusionsOf the eight PON SNVs examined, two (rs854560 and rs662) were associated with PCOS risk. These 1.4-fold increased risk effects rendered Asians susceptible to PCOS. High statistical power, high significance, zero to low-level heterogeneity, robustness and lack of bias in the core outcomes underpinned the strong evidence for association.