Association of TNF-alpha, IL-6 and IL-1beta gene polymorphisms with polycystic ovary syndrome: A meta-analysis

Abstract

Background: Several studies on the association of TNF-alpha (-308 G/A), IL-6 (-174 G/C) and IL-1beta (-511 C/T) polymorphisms with polycystic ovary syndrome (PCOS) risk have reported conflicting results. The aim of the present study was to assess these associations by meta-analysis. Results: A total of 14 eligible articles (1665 cases/1687 controls) were included in this meta-analysis. The results suggested that there was no obvious association between the TNF-alpha (-308 G/A) polymorphism and PCOS in the overall population or subgroup analysis by ethnicity, Hardy-Weinberg equilibrium (HWE) in controls, genotyping method, PCOS diagnosis criteria, and study sample size. Also, no obvious association was found between the TNF-alpha (-308 G/A) polymorphism and obesity in patients with PCOS (body mass index [BMI] ≥ 25 kg/m2 vs. BMI < 25 kg/m2). Regarding the IL-6 (-174 G/C) polymorphism, also no association was found in the overall population in heterozygote comparison, dominant model, and recessive model. Even though an allelic model (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.41-0.96) and a homozygote comparison (OR = 0.52, 95% CI = 0.30-0.93) showed that the IL-6 (-174 G/C) polymorphism was marginally associated with PCOS. Further subgroup analysis suggested that the effect size was not significant among HWE in controls (sample size ≤ 200) and genotyping method of pyrosequencing under all genetic models. Similarly, there was no association between the IL-1beta (-511 C/T) polymorphism and PCOS in the overall population or subgroup analysis under all genetic models. Furthermore, no significant association was found between the IL-1beta (-511 C/T) polymorphism and several clinical and biochemical parameters in patients with PCOS. Conclusions: The results of this meta-analysis suggest that the TNF-alpha (-308 G/A), IL-6 (-174 G/C), and IL-1beta (-511 C/T) polymorphisms may not be associated with PCOS risk. However, further case-control studies with larger sample sizes are needed to confirm our results.