Interleukin-1 gene cluster variants and recurrent pregnancy loss among North Indian women: retrospective study and meta-analysis

The aim of this study was to determine whether or not interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β) and IL-1 receptor antagonist (IL-1RA) polymorphisms are associated with risk of unexplained recurrent pregnancy loss (RPL) among North Indian women. This retrospective case–control study examine 200 well-characterized RPL cases for IL-1 gene cluster variants, determined by restriction fragment length polymorphism-PCR. The observed allele, genotype and haplotype distributions were compared with those obtained from 300 ethnically matched negative controls. Invariant distribution of IL-1 gene cluster single-nucleotide polymorphisms was observed among RPL cases and controls. Meta-analysis of IL-1β −511, +3953 and IL-1RN 86-bp variable number tandem repeat from the reported literature and this study did not reveal any significant association with the risk of RPL. In conclusion, no significant difference between RPL and control groups was observed at the allele, genotype or haplotype levels when tested for association using the dominant, recessive and additive models of inheritance for IL-1 gene cluster variants. As far as is known, this is the first report from India pertaining to IL-1 gene cluster variants’ association with the risk of RPL from North India.One of the most unfortunate complications of incomplete motherhood is recurrent pregnancy loss (RPL) particularly of unknown aetiology. RPL is defined as the loss of three or more consecutive pregnancies before the 24th week of gestation. Both genetic and environmental factors may play a role in the maintenance of pregnancy. From a traditional immunological perspective, survival of the semi-allogenic fetus is dependent on suppression of the maternal immune response. However, the function of immune cells changes during pregnancy, no generalized suppression of the maternal immune response has been recorded. Cytokines in the interleukin-1 system (IL-1α, IL-1β and receptor antagonist (IL-1RA)) are produced at the fetal–maternal interface during early pregnancy and are believed to influence the immune responsiveness of Th1/Th2 cells and has been implicated in the establishment of successful pregnancy. This study examines IL-1 gene cluster variants among well-characterized RPL patients and compares them with those of healthy controls. IL-1 gene cluster single-nucleotide polymorphisms were found to be invariably distributed among RPL patients and controls. Meta-analysis of results of IL-1β −511, IL-1β +3953 and IL-1RN 86-bp variable number tandem repeat studies in RPL, as reported previously, also did not show any effect of these variations on the risk of occurrence of the disease.