Association of CYP17 gene polymorphism (rs743572) with polycystic ovary syndrome

Introduction

Polycystic ovary syndrome (PCOS) affects 4–20% of women of reproductive age. The contribution of genetic factors to the etiology of PCOS is 79%, and the contribution of the environment, lifestyle and individual history is 21%. It is believed that the increased production of androgens in PCOS is a consequence of dysregulation of various genes involved in the synthesis of steroid hormones, such as CYP11, CYP17 and CYP19. Conflicting data on the association of the CYP17 gene polymorphism (rs743572) with PCOS determined the purpose of this meta-analysis - to study this association in a larger general population in order to determine whether polymorphism in the CYP17 T/C promoter is associated with an increased risk of PCOS.

Methods

A systematic search was carried out in various databases for articles on the relationship between rs743572 polymorphism of gene CYP17 and PCOS risk published up to May 2021. The articles were analyzed in accordance with the recommendations for systematic reviews and meta-analyzes (PRISMA). The criteria for inclusion of studies in the meta-analysis were: (i) case-control studies with healthy populations as controls; (ii) a study describing the diagnostic criteria for PCOS, sources of cases and controls; (iii) studies of genetic associations showing the frequency of genotypes of the studied polymorphism and PCOS in humans; (iv) sufficient genotype data to calculate odds ratio (OR) and 95% confidence interval (CI). The control HWE was first assessed for each study using the chi-square test (χ2). Meta-analysis was performed using Review Manager version 5.4. Odds ratios (OR) with a 95% confidence interval (CI) were used to assess the strength of the association between the rs743572 polymorphism of gene CYP17 and PCOS. Pooled OR was calculated for dominant (CC + TC vs. TT), recessive (CC vs. TC + TT), and allelic (C vs. T) models, as well as for homozygous (CC vs. TT) and heterozygous (TC vs. TT) models.

Results

Out of 577 potentially relevant articles, 17 articles were selected for eligibility assessment after excluding irrelevant and duplicate articles. 2283 cases and 2200 controls were evaluated to identify the relationship between the rs743572 polymorphism of the CYP17 gene and PCOS. Carriage of allele C was considered to increase the risk of PCOS. A significant association with PCOS risk was found for rs743572 in the general population using dominant, allelic and heterozygous models: (p = 0.005, OR = 1.41, 95% CI 1.11–1.79; p = 0, 006, OR = 1.28, 95% CI 1.07–1.53; p = 0.01, OR = 1.38, 95% CI 1.07–1.77), respectively. An association between this polymorphism and PCOS risk was not found in the recessive and homozygous models: (p = 0.16, OR = 1.21, 95% CI 0.93–1.58; p = 0, 08, OR = 1.31, 95% CI 0.96–1.78), respectively. Subgroup analysis according to the ethnicity of the participants showed significant associations between Asian and European populations: a higher association was found among Asian populations in the dominant model (p = 0.04, OR = 1.59, 95% CI 1.02–2.48).

Conclusions

The meta-analysis showed an increased risk of PCOS in carriers of the C allele rs743572, thus, polymorphism rs743572 is a risk factor for PCOS, especially in the Asian population. To determine the genetic risks of PCOS, further research is needed on different haplotypes and their association with PCOS risk.