Interleukin 10 Gene Promoter Polymorphisms in Women with Pregnancy Loss: Preferential Association with Embryonic Wastage1

Abstract

Interleukin 10 (IL10) is associated with maternal immunotolerance. IL10 also down-regulates decidual cell tissue factor expression, the main molecule triggering coagulation activation: this antithrombotic effect may protect the umbilicoplacental vasculature from the 10th wk of gestation onward. IL10 down-regulation may thus dispose to early pregnancy loss (PL) due to maternal immunotolerance defect or late pregnancy failure due to placental vascular insufficiency. IL10 gene promoter polymorphisms associated with cytokine down-regulation may help to identify the actual and probable mechanisms of IL10 modulation in pregnancy outcomes. We investigated the following four IL10 promoter polymorphisms associated with IL10 down-regulation: two single-nucleotide polymorphisms rs1800871 and rs1800872 and two polymorphic CA repeat microsatellites IL10 X78437.2:g8134CA(14_29) and IL10 X78437.2:g.5325CA(11_15). Each microsatellite was analyzed as a biallelic polymorphism. Based on a review of the literature, we define a short allele and a long allele for each microsatellite. We compared their frequencies in early PL occurring before 10 wk of amenorrhea (n = 342) and in PL occurring later on (n = 123). The mutated alleles rs1800871T (odds ratio, 3.083; 95% confidence interval, 1.984-4.792) and rs1800872A (odds ratio, 3.013; 95% confidence interval, 1.924-4.719) were associated with early PL. The haplotype rs1800872A/rs1800871T/X78437.2:g.8134CA[14_25]/X78437.2:g.5325CA[11_13], which includes the two mutated alleles, was significantly associated with the risk of early PL in a dose-dependent manner. Positivity for one haplotype was significantly associated with a 5.6-fold increase in the risk of early pregnancy failure, and positivity for two haplotypes was associated with an 8-fold increase in risk. In women with PL, some polymorphisms of the IL10 gene promoter seem to be constitutional risk factors for early (embryonic) pregnancy failure.