Problem Cytokine gene polymorphism studies in women with recurrent spontaneous abortion (RSA) are reviewed to provide comprehensive understanding and a direction for the future investigation.
Method of study A search of PubMed was made to identify the published data between 2001 and 2007 regarding RSA and cytokine gene polymorphisms.
Results Either allele and/or genotype frequencies of the following polymorphisms were reported to be significantly different between women with RSA and controls: IFN-γ +874A→T, TA (P = 0.01), AA (P = 0.04); IL-6, −634C→G CG/GG (P = 0.026); IL-10, −592C→A CC (P = 0.016); IL-1B −511C (P = 0.035), −31T (P = 0.029); IL-1RA, IL1RN*2 (P = 0.002), and IL1RN*3 (P = 0.002). None of these studies was repeatedly reported by others to be significantly different. Among these, four cytokine polymorphisms (IFN-γ, +874A→T; IL-1B −511C; IL-1RA, IL1RN*2, IL1RN*3) were refuted by others and rest of them were studied once.
Conclusion Multiple cytokine polymorphisms were reported to be associated with RSA. However, a majority of studies were not confirmed by other investigators or refuted by others. Inconsistent study results might be related to: (i) the production of these cytokines is partly under genetic controls and other factors affect cytokine levels; (ii) ethnic background, environmental factors, and selection criteria for study populations are different and (iii) the possibilities exist that multiple cytokine gene polymorphisms or other genes in linkage disequilibrium may play a role in RSA.