Cytokine gene polymorphisms in recurrent pregnancy loss of unknown cause.

PROBLEM

According to previous investigations, certain cytokines may play a role in recurrent pregnancy loss (RPL). Significantly different levels of Th1/Th2 cytokines are produced by normal pregnant women compared with women with RPL of unknown cause.

OBJECTIVE

We have studied the polymorphism of cytokine genes which are related to the amount of the cytokine produced. High (H), intermediate (I) and low (L) cytokine responses can be predicted from the cytokine genotype.

MATERIAL AND METHODS

The genetic polymorphism of Th1 cytokine [i.e. interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha] and Th2 cytokines [i.e. interleukin (IL)-6, IL-10] and the transforming growth factor (TGF)-beta were studied by polymerase chain reaction-sequence specific primers (PCR-SSP) in the DNA of PBC from 41 women with RPL and 54 control women who had at least two children and without known pregnancy losses.

RESULTS

The results showed: (i) no evidence of associations between patients and controls concerning the Th1: TNF-alpha; the Th2: IL-6 and IL-10 and the TGF-beta genotype, (ii) significative association between RPL versus controls concerning IFN-gamma +874 A --> T: T/A genotype was increased in the patient group in comparison with the control group (65% versus 35.8%) (P = 0.01) and there was a statistical disminution in the frequency of the A/A (L) genotype between the patient groups in comparison with the control group (20% versus 41.5%) (P = 0.04).

CONCLUSION

This finding would support the concept of involvement of IFN-gamma +874 A --> T in the pathogenesis of RPL of unknown cause in the Caucasian Argentine population.