Relationship between cytokine gene polymorphisms and recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA), defined as three or more sequential abortions before the twentieth week of gestation. Some studies have led to the awareness that immunological factors play an important role in establishing a successful pregnancy. The aim of present study was to investigate the relationship between RSA and polymorphisms of cytokine genes coding for TNF-α (-308 G→A, -238 G→A), TNF-β (+252 G→A) as Th1 or pro-inflammatory factors as well as IL-6 (-634 G→C, -174 G→C), IL-10 (-1082 A→G, -819 C→T, -592C→A) as Th2 cytokines in women with RSA compared with healthy women. A total of 284 women with RSA and 284 control women with at least two successful pregnancies and no history of abortion were included in the study. The polymerase chain reaction (PCR), allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) or PCR-RFLP (restriction fragment length polymorphism) methods were used for genotyping. In addition, the ELISA was conducted to investigate four cytokine serum levels in women with RSA and healthy women. Results showed that: TNF-α -308G/A, IL-6 -174 G/C and IL-10 -819 G/C polymorphisms showed statistically significant differences between the RSA patients and controls (P=0.008, P=0.0005 and P=0.03 separately). Levels of four cytokines in the serum showed that there were no significant differences in TNF-α and TNF-β between patients and control (P>0.05), while the level of IL-6 and IL-10 were lower than control group and the differences were statically significant (P<0.05). This study demonstrated a possible association between TNF-α -308, IL-6 -174 and IL-10 -819 promoter polymorphism and RSA.