Yue Jun, Tong Yu, Zhou Jing, Liu Qingqing, Yang Jiyun
Department of Gynecology & Obstetrics, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, No. 32, Section 2, the Western First Round Road, Chengdu 610072, China.
Laboratory of Early Developmental and Injuries, West China Institute of Woman and Children's Health, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin Nanlu, Chengdu 610072, China.
Int J Mol Sci. 2015 Feb 16;16(2):4180-9. doi: 10.3390/ijms16024180.
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.
复发性流产（RM）女性体内的白细胞介素-18（IL-18）水平显著低于无特发性RM的女性。先前已确定IL-18启动子单核苷酸多态性会影响IL18基因转录活性并影响IL-18蛋白产生水平。本研究的目的是评估IL-18基因多态性是否为中国汉族人群特发性RM的危险因素。研究对象包括484例特发性RM患者和468例对照。评估了IL-18基因中的三种多态性（rs360717、rs187238、rs1946518）以及血清IL-18浓度。rs187238变异体在加性和隐性遗传模型中与RM表现出显著关联（加性模型p = 1.05×10⁻⁴，显性模型p = 0.025，隐性模型p = 2.43×10⁻⁵）。相比之下，rs360717和rs1946518与RM无显著关联。RM病例的血清IL-18水平显著低于对照组（111.98±93.13对148.74±130.51 pg/mL，p = 7.42×10⁻⁷）。在本研究人群（包括病例组和对照组）中，rs187238纯合突变体（CC）的血清IL-18水平低于纯合野生型（GG）（98.31±86.46对131.87±115.02 pg/mL，p = 0.015）。这些结果表明，IL-18水平降低和rs187238变异体可能与中国汉族人群特发性RM的发病机制有关。
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