Polymorphisms in Inflammatory Mediator Genes and Risk of Preeclampsia in Taiyuan, China

Abstract

Excessive maternal inflammatory response is involved in the pathogenesis of preeclampsia. Few epidemiologic studies have investigated the associations between genetic variations in the inflammatory mediator genes and preeclampsia risk, and these studies have reached inconsistent results. We examined 31 single-nucleotide polymorphisms in IL-1A, IL-1B, IL-1R1, IL-2RA, IL-5RA, IL-6, IL-6R, TNFSF11, TNFRSF11A, IL-28RA, IRAK4, and KIT genes and the risk of preeclampsia and its clinical subtypes in a nested case-control study including 203 preeclampsia cases and 233 controls. We found that IL-1R1, IL-5RA, IL-6R, and TNFSF11 were associated with the risk of preeclampsia. Although the significant associations observed for preeclampsia overall were mainly seen for late-onset preeclampsia and severe preeclampsia, IL-6R (rs2229238) and TNFSF11 (rs9525643) polymorphisms were associated with the risk of early-onset preeclampsia. TNFSF11 (rs2200287 and rs2148072) polymorphisms were associated with risk of mild preeclampsia. Our study provided the first evidence that genetic variations in inflammatory mediator genes IL-1R1, IL-6R, TNFSF11, and IL-5RA were associated with preeclampsia risk, and the risk varied by preeclampsia subtypes.

Association of TNFSF11 rs2200287 and TNFSF11 rs2148072 gene polymorphisms in preeclampsia

“…TNFSF11 SNPs (rs2200287 and rs2148072) have been linked to PE risk, according to Wu et al. Women with the TNFSF11 rs2200287 AA genotype had a significantly higher risk of mild PE than women with the GG genotype (ORAA = 6.22; 95% CI: [2.0618.80]); the same impact was shown with the TNFSF11 rs2148072 TT genotype against the CC genotype (ORTT = 6.83; 95% CI: [2.242.85]), which was linked to Wu W et al 6 . There is a substantial association between inflammation‐promoting TNF‐Αand PE genotypes, according to Azizah et al.…”

The role of interleukins in preeclampsia: A comprehensive review

“…A meta‐analysis that included 1888 patients and 2947 controls found no evidence of association between TNF‐α G308A GG genotype and PE (pooled OR = 0.98, 95% CI: [0.76‐1.25]). Novel data from Wu et al showed that SNPs of TNFSF11 (rs2200287 and rs2148072) are related to PE risk. Specifically, women who carried TNFSF11 rs2200287 AA genotype compared to GG genotype seemed to have significantly increased risk of mild PE (OR AA = 6.22; 95% CI: [2.06‐18.80]); the same effect was observed for the TNFSF11 rs2148072 TT genotype compared to the CC genotype (OR TT = 6.83; 95% CI: [2.24‐20.85]).…”

Association of IL-10 -819C/T, -592A/C polymorphisms with the risk of preeclampsia

“…[ 6 – 8 ] In addition, several studies have identified that single nucleotide polymorphisms (SNPs) have been involved in the pathogenesis of PE, such as cytokines genes SNPs. [ 9 – 11 ]…”