Association between Genetic Polymorphisms in Interleukin Genes and Recurrent Pregnancy Loss – A Systematic Review and Meta-Analysis

<div><p>Interleukins are a group of immunomodulatory proteins that mediate a variety of immune reactions in the human body. To investigate the association between interleukin gene polymorphisms and recurrent pregnancy loss (RPL), we reviewed 21 studies from MEDLINE, EMBASE, OVID SP and PubMed to evaluate RPL-related interleukin gene polymorphisms. Meta-analysis was performed on 12 of the polymorphisms, and a review included the others. Our integrated results indicated that IL-1β (-511C/T) (P = 0.02, 95% CI 0.77[0.62,0.96]), IL-6 (-634C/G) (P<0.001, 95% CI 2.91[2.01,4.22]), IL-10 (-1082G/A, –819T/C) (P = 0.01, 95% CI 0.80[0.67,0.96]; P<0.01, 95% CI 0.66[0.49,0.89]), and IL-18 (-137G/C, -105G/A) (P<0.01, 95% CI 1.69[1.24,2.31]; P = <0.01, 95% CI 1.41[1.17,1.70]) consistently associated with RPL after meta-analysis. IL-17A rs2275913 and IL-17F rs763780, IL-21 rs2055979 and rs13143866, IL-1β (-31C/T), IL-6 (-2954G/C), and IL-10 (-536A/G) were reported only once as having a significant association with RPL. The potential mechanism underlying miscarriage and these polymorphisms and future research directions are also discussed.</p></div

Association between the IL-1β (-511 C/T) polymorphism and RPL under a recessive genetic model.

<p>Association between the IL-1β (-511 C/T) polymorphism and RPL under a recessive genetic model.</p

Association between the IL-18 (-137G/C) polymorphism and RPL under dominant and recessive genetic models.

<p>Association between the IL-18 (-137G/C) polymorphism and RPL under dominant and recessive genetic models.</p

Association between the IL-10 (-1082G/A) (A, B) and IL-10 (–819 T/C) (C, D) polymorphisms and RPL under a dominant and recessive genetic models.

<p>Association between the IL-10 (-1082G/A) (A, B) and IL-10 (–819 T/C) (C, D) polymorphisms and RPL under a dominant and recessive genetic models.</p

Flow diagram detailing selection of studies for inclusion.

<p><i>From</i>: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). <i>P</i>referred <i>R</i>eporting <i>I</i>tems for <i>S</i>ystematic Reviews and <i>M</i>eta <i>A</i>nalyses: The PRISMA Statement. Plos Med 6(7): e1000097. doi: <a href="http://dx.doi.org/10.1371/journal.pmed1000097" target="_blank">10.1371/journal.pmed1000097</a><b>For more information, visit</b><a href="http://www.prisma-statement.org" target="_blank">www.prisma-statement.org</a>.</p

Association between the IL-6 (-634C/G) polymorphism and RPL under a recessive genetic model.

<p>Association between the IL-6 (-634C/G) polymorphism and RPL under a recessive genetic model.</p

Corresponding SNP IDs and relative locations of these polymorphisms.

<p>Corresponding SNP IDs and relative locations of these polymorphisms.</p

Methodological characteristics and quality control of all eligible articles.

<p>Methodological characteristics and quality control of all eligible articles.</p