Genetic variant in interleukin-18 is associated with idiopathic recurrent miscarriage in Chinese Han population.

Jun Yue,Jing Zhou,Yu Tong,Jiyun Yang,Qingqing Liu

doi:10.3390/ijms16024180

Abstract

Levels of IL-18 were significantly lower in women with recurrent miscarriage (RM) than those without idiopathic RM. IL-18 promoter single nucleotide polymorphisms were previously identified to have an impact on IL18 gene transcription activity and influence the level of IL-18 protein production. The aim of this study was to evaluate whether IL-18 gene polymorphisms are risk factors for idiopathic RM in Chinese Han population. Study subjects comprised of 484 idiopathic RM patients and 468 controls. Three polymorphisms (rs360717, rs187238, rs1946518) in IL-18 gene and serum IL-18 concentrations were assessed. rs187238 variant exhibits significant association with RM in additive and recessive genetic model (additive model p = 1.05 × 10−4, dominant model p = 0.025, recessive model p = 2.43 × 10−5). In contrast, rs360717 and rs1946518 are not significantly associated with RM. Serum IL-18 levels are significantly lower in RM cases than in control (111.98 ± 93.13 versus 148.74 ± 130.51 pg/mL, p = 7.42 × 10−7). There are lower levels of serum IL-18 in rs187238 homozygous mutant (CC) than homozygous wild-type (GG) in this study population, including cases and control groups (98.31 ± 86.46 versus 131.87 ± 115.02 pg/mL, p = 0.015). These results suggest that reduced IL-18 levels and rs187238 variant may contribute to pathogenesis of idiopathic RM in Chinese Han population.

Highlights

Recurrent miscarriage (RM) is the occurrence of three or more repeated pregnancies that end in loss of the fetus, usually before 20 weeks of gestation
While lower age at menarche, higher irregular menstrual history (%) and number of pregnancies were seen in the recurrent miscarriage (RM) group
Much work has been done to identify the cause of idiopathic RM, its reason remains unknown [1]

Summary

Introduction

Recurrent miscarriage (RM) is the occurrence of three or more repeated pregnancies that end in loss of the fetus, usually before 20 weeks of gestation. RM affects 1%–5% of women who attempting to bear children [1]. A series of etiological factors have been identified for miscarriage, including uterine anomaly, chromosomal abnormalities, endocrine dysfunction, thrombophilia, immune disorders, life style factors and maternal infections [1]. At least 50% of the RM patients have no deviations in any applied diagnostic test. The exact underlying etiology is still poorly understood. There is growing evidence that RM has genetic susceptibility [2,3,4]

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