Possible Association of IL-4 VNTR Polymorphism with Susceptibility to Preeclampsia

Abstract

Preeclampsia (PE) is a pregnancy-specific disorder that results in maternal mortality and morbidity. Growing evidence indicated that cytokines are involved in the pathogenesis of PE and interleukin-4 VNTR polymorphism could be implicated in altering the PE risk. The aim of this study was to evaluate the possible association between IL-4 VNTR polymorphism and susceptibility to PE in Iranian population for the first time. Genetic polymorphism was evaluated in 192 PE and 186 healthy control women by polymerase chain reaction method. We found that the VNTR polymorphism of IL-4 gene has significantly increased the risk of preeclampsia (RP2/RP1 versus RP1/RP1, OR, 2.8 [95% CI, 1.7 to 8.8]; P = 0.0001 and RP2/RP2 versus RP1/RP1; P = 0.002). The results showed that carriage of IL-4 VNTR RP2 allele has positive association with preeclampsia susceptibility.

The role of interleukins in preeclampsia: A comprehensive review

“…The same effect was also observed in a recent Chinese study including 453 participants . Moreover, as shown by an Iranian study, the VNTR polymorphism of IL‐4 intron 3 nearly tripled the risk of the disease (OR: 2.8, 95% CI: [1.7‐8.8]) . However, the above outcomes were disputed by a Taiwanese study including 203 patients, which found no association of the −590 and VNTR polymorphisms with PE .…”

“…More specifically, polymorphisms on the promoter regions, introns or exons of interleukin genes, alter the transcriptional activity and may result in aberrant interleukin production and potentially a precipitated inflammatory response. Another possible route that mediates the increased PE risk associated with certain alleles is abnormal mRNA splicing . However, these findings should be evaluated with caution, as there is a lack of large‐scale prospective studies and the ethnicity‐based heterogeneity across studies is high.…”

Interleukin-1 Receptor Antagonist (<em>IL1RA</em>) and Interleukin-4 (<em>IL4</em>) Genes Variable Number Tandem Repeats (VNTRs) Are Associated with Adiposity in Malaysian Subjects

“…The IL1RA VNTR may have functional significance as the repeated sequence contains possible binding sites for transcription factors [9]. A review by Witkin et al 2002 [10] summarized that individuals homozygous for allele II have a more prolonged and more severe proinflammatory immune response than persons with other IL1RA genotypes, which might be beneficial when combating infectious agents [39] or neoplasms [40], but is detrimental for those with chronic inflammatory conditions [41] or who are pregnant [42].…”

Association between interleukin 4 (IL-4) VNTR, gene polymorphism, and breast cancer susceptibility in Iranian population: experimental and web base analysis

“…Interleukin 4 (IL-4) is an important differentiation cytokine produced by Th2 and activates Th2 development. Th2 subset of lymphocytes have the responsibility of tumor cell clearance by the means of granulocytes and Eosinophils activation and also inhibition of angiogenesis (16)(17)(18). As a further matter, Th2 subset antagonize IFN-γ, inhibit macrophage activation and its anti-tumor function on variety of cancers such as: colon, breast cancer and renal cancer were reported by some studies (19,20).…”