title: Associations between TNF-α and interleukin gene polymorphisms with polycystic ovary syndrome risk: a systematic review and meta-analysis.
abstract: BACKGROUND
  The associations between TNF-α and Interleukin gene polymorphisms and polycystic ovary syndrome (PCOS) risk have been studied in numerous epidemiological studies, but the results remain controversial. To investigate whether these polymorphisms facilitate susceptibility to PCOS, we conducted a comprehensive systematic review and meta-analysis.
  
  
  METHODS
  PubMed, Embase, Web of Science, Medline, CNKI, and Google Scholar were searched to obtain the genetic association studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (OR) with corresponding 95 % confidence intervals (CI) were used to assess the strengths of the associations. Funnel plots and Egger's tests were performed to test for possible publication bias. All statistical analyses were performed using Review Manager 5.2 and STATA11.0.
  
  
  RESULTS
  Eighteen articles were included in the final meta-analysis. The studies involved the following polymorphisms: TNF-α -308G > A, TNF-α -805C>T, TNF-α -1031 T>C, IL-1A -889C>T, IL-1B -511C>T, IL-1B +3953 T>C, IL-6 -174G>C, IL-10 -819C>T, IL-10 -1082A>G, IL-18 -607C>A, and IL-18 -137G>C. Our results show a significant association between PCOS risk and the TNF-α -1031 T>C polymorphism (For TC+CC vs. TT: OR=2.09, 95 % CI=1.58-2.76, p<0.0001. For C allele vs. T allele: OR=1.67, 95 % CI=1.33-2.09, p<0.0001) and between PCOS risk and the IL-6 -174>C polymorphism (For CC+GC vs. GG: OR=0.49, 95 % CI=0.25-0.95, p=0.03. For CC vs. GG: OR=0.48, 95 % CI=0.28-0.80, p=0.005. For C vs. G: OR=0.60, 95 % CI=0.42-0.87, p=0.007). No associations were found with the other genetic models.
  
  
  CONCLUSIONS
  The results of the meta-analysis suggest positive associations between the TNF-α -1031 T>C and IL-6 -174G>C polymorphisms and the risk of PCOS. No associations are found between PCOS risk and the TNF-α -308G>A, TNF-α -805C>T, IL-1A -889C>T, IL-1B -511C>T, IL-1B +3953C>T, IL-10 -819C>T, IL-10 -1082 A>G, IL-18 -607C>A, and IL-18 -137G>C polymorphisms. However, due to the heterogeneity and low quality of the studies related to PCOS polymorphisms in the meta-analysis, the results should be interpreted with caution. Future multi-ethnicity studies of homogeneous populations of PCOS patients with larger sample sizes and well-matched controls are needed.
authors.affiliation: Department of Gynaecologic Oncology, Sichuan Cancer Hospital and Institute, No 55, Section 4 of Renmin South Road, Chengdu, 610041, Sichuan, People's Republic of China, wuhaijing128@126.com.
authors.forename: Haijing
authors.initials: H
authors.lastname: Wu
authors.forename: Ke
authors.initials: K
authors.lastname: Yu
authors.forename: Zhenghui
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha