Analysis of Polymorphisms in Interleukin-10, Interleukin-6, and Interleukin-1 Receptor Antagonist in Mexican-Mestizo Women with Pre-eclampsia

Abstract

Due to the fact that studies seeking associations of polymorphisms in regulatory regions of cytokine genes with pre-eclampsia (PE) have not always been consistent in different population analyses, the aim of this study was to investigate the possible association between rs1800896 of interleukin-10 (IL-10), rs1800795 of interleukin-6 (IL-6), and the variable number of tandem repeats (VNTR) in intron 2 of interleukin-1 receptor antagonist (IL-1Ra), as well as gene-gene interactions between these three polymorphisms with the presence of PE in Mexican-Mestizo women and one Amerindian population from México (Maya). A case-control study was performed where 411 pre-eclamptic cases and 613 controls were genotyped. For the rs1800896 of IL-10 and rs1800795 of IL-6, we used real-time polymerase chain reaction (PCR) allelic discrimination and for the VNTR of IL-1Ra, PCR. Allele frequency differences were assessed by Chi-squared test; logistic regression was used to test for associations; a gene-gene interaction was conducted. Genotypic and allelic distribution of the polymorphisms was similar in our population. The estimated of the gene-gene interaction between the polymorphisms did not differ significantly. However, we observed important differences in the distribution of the alleles and genotypes of the three polymorphisms analyzed between Mestiza-Mexicanas and Maya-Mestizo women. In conclusion, we did not find an association between polymorphisms in IL-10, IL-6, and IL-1Ra and PE in Mexican-Mestizo and MayaMestizo women. To our knowledge, this is the first time that these three polymorphisms were analyzed together with gene-gene interaction in women with PE.

Polymorphisms in interleukin-6 and interleukin-10 may be associated with risk of preeclampsia

“…In addition, Pissetti et al (2014) and Vural et al (2010) carried out an investigation involving expectant women in Turkey and Brazil, revealing that the IL-10 -1082A/G sequence variant is associated with preeclampsia susceptibility. However, Valencia Villalvazo et al (2012) and Stonek et al (2008) failed to detect a correlation between this condition and polymorphisms in IL-6 and IL-10. In the present study, we identified a significant relationship between the IL-10 -592A/C variant and risk of developing preeclampsia among pregnant women in China.…”

“…Previous investigations have tested the association between IL-10 gene polymorphisms and preeclampsia development, but with conflicting results (Stonek et al, 2008;Vural et al, 2010;Valencia Villalvazo et al, 2012;Pissetti et al, 2014;Sowmya et al, 2014;Song and Zhong, 2015;Liu et al, 2015). Liu et al (2015) and Sowmya et al (2014) reported the IL-10 -819T/C genetic variant to be associated with increased preeclampsia risk in pregnant women in China and India.…”

“…A deficiency in placental IL-10 has been reported in pregnant women with preeclampsia in comparison to control subjects, and serum IL-10 level is associated with genetic variations in the IL-10 promoter (Makris et al, 2006). Several previous studies have analyzed the association between IL-10 gene polymorphisms and development of preeclampsia, but their results conflict (Vural et al, 2010;Xie et al, 2011;Valencia Villalvazo et al, 2012;Liu et al, 2015). Moreover, none has investigated the relationship between IL-6 genetic variation and risk of this developing this condition in pregnant Chinese women.…”

Genetic variations in IL1A and IL1RN are associated with the risk of preeclampsia in Chinese Han population

“…Faisel et al studied on 133 PE patients and 112 controls from Finland, suggesting an association between the variable copy number of 86-bp tandem repeats (VNTR) of the IL1RN polymorphism and PE32. However, Valencia et al did not find the associations between polymorphism of IL1RN VNTR and PE in Mexican-Mestizo and Maya-Mestizo women33. And polymorphism of rs16944 and rs1143634 in IL-1β showed no associations with the risk of PE in Taiwanese34.…”

The role of interleukins in preeclampsia: A comprehensive review

“…The impact of the variable number of tandem repeats (VNTR) in intron 2 of IL‐1Ra gene remains controversial; although an Iranian study indicated the protective role of VNTR polymorphism, a study in 1024 Mexican women did not found any significant association . Moreover, a Brazilian study that explored the role of single nucleotide polymorphisms (SNPs) in IL‐1β concluded that the incidence of TC and TT genotype in rs1143630 was significantly higher in PE women .…”