Cytokine gene polymorphisms in recurrent spontaneous abortions: A comprehensive review

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-gamma +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-gamma, +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.