European Cytokine Network


Genetic variations in the interleukin-21 gene and the risk of recurrent idiopathic spontaneous miscarriage Volume 22, issue 2, June 2011

Research Unit of Biology and Genetics of Cancer and Haematological and Autoimmune diseases, Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain, Department of Anesthesia, CHU Farhat Hached, Sousse, Tunisia, Department of Obstetrics/Gynecology, CHU Farhat Hached, Sousse, Tunisia

Objectives. Insofar as recurrent spontaneous miscarriage (RSM) is linked with dysregulated immunity and inflammatory changes, and given the pro-inflammatory role of interleukin-21 (IL-21), we examined the association between IL-21 polymorphisms and RSM. Methods and results. IL-21 rs2055979, rs13143866, rs9992580, and rs4833837 were genotyped in 235 cases of RSM and 235 controls. Regression analysis was employed in assessing the contribution of IL-21 variants to the overall RSM risk. Higher minor allele and genotype frequencies of rs2055979 and rs13143866, but not rs9992580 or rs4833837, were seen in RSM patients than in the controls. IL-21 haplotype [rs9992580/rs4833837/rs2055979/rs13143866] analysis revealed a lower frequency of the <u xmlns="http://www.thomsondigital.com/xml/ja/dtd">T</u><u xmlns="http://www.thomsondigital.com/xml/ja/dtd">G</u>CG haplotype, and a higher frequency of the G<u xmlns="http://www.thomsondigital.com/xml/ja/dtd">G</u>CG and GA <u xmlns="http://www.thomsondigital.com/xml/ja/dtd">AA</u> haplotypes in patients, thus conferring protection from or a susceptibility to RSM by these haplotypes respectively. Regression analysis confirmed the association of <u xmlns="http://www.thomsondigital.com/xml/ja/dtd">T</u><u xmlns="http://www.thomsondigital.com/xml/ja/dtd">G</u>CG [OR (95%CI)=0.09 (0.05-0.16)], and G<u xmlns="http://www.thomsondigital.com/xml/ja/dtd">G</u>CG [OR (95%CI)=2.52 (1.34-4.54)] and GA <u xmlns="http://www.thomsondigital.com/xml/ja/dtd">AA</u> [OR (95%CI)=4.02 (2.20-7.70)] haplotypes, after adjusting for age and BMI. Conclusions. Our findings indicate that IL-21 is a novel susceptibility gene for RSM.