Nair Rohini Ravindran, Khanna Anuradha, Singh Kiran
Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India.
Mol Biol Rep. 2014 Sep;41(9):5719-27. doi: 10.1007/s11033-014-3443-8. Epub 2014 Jun 22.
An appropriate ratio of interleukin 1 beta to interleukin 1 receptor antagonist (IL1Ra) is required for successful pregnancy. Our objective was to study the genetic association between IL1RN variable numbers of tandem repeat (VNTR) polymorphism and recurrent pregnancy loss (RPL). To analyze the association between IL1RN VNTR allele and RPL, we investigated the IL1RN VNTR polymorphism in 136 RPL patients and in 200 healthy control women. Meta-analysis on this polymorphism was conducted to support our findings. PCR based approach was used to analyze IL1RN VNTR polymorphism and it was further confirmed by sequencing. Systematic review and meta-analysis was done using electronic database (Pub-Med, Google Scholar and Ovid) up to February 27, 2013. This meta-analysis was assessed by comprehensive meta-analysis software version 2. For meta-analysis 549 cases and 1,450 controls were included. The frequency of IL1RN genotype 2/2 was significantly higher in RPL compared to control group (AORs 3.10, 95 % CI 1.58-6.11, p = 0.001). The presence of rare allele also increased the risk of RPL significantly (ORs 1.63, 95 % CI 1.16-2.29, p = 0.004). The meta-analysis stratified by ethnicity showed that individuals with allele 2 had increased risk of RPL (OR 1.29, 95 % CI 1.04-1.61, p = 0.01), in Asians population by using fixed model. However the data of the present study clearly suggests that IL1RN VNTR polymorphism is a genetic risk factor for pregnancy loss in the study population.
成功妊娠需要白细胞介素1β与白细胞介素1受体拮抗剂(IL1Ra)的适当比例。我们的目的是研究白细胞介素1受体拮抗剂(IL1RN)可变数目串联重复序列(VNTR)多态性与复发性流产(RPL)之间的遗传关联。为了分析IL1RN VNTR等位基因与RPL之间的关联,我们调查了136例RPL患者和200名健康对照女性的IL1RN VNTR多态性。对该多态性进行荟萃分析以支持我们的研究结果。采用基于聚合酶链反应(PCR)的方法分析IL1RN VNTR多态性,并通过测序进一步证实。使用电子数据库(PubMed、谷歌学术和Ovid)进行系统评价和荟萃分析,截至2013年2月27日。该荟萃分析由综合荟萃分析软件版本2进行评估。荟萃分析纳入了549例病例和1450例对照。与对照组相比,RPL患者中IL1RN基因型2/2的频率显著更高(比值比3.10,95%可信区间1.58 - 6.11,p = 0.001)。罕见等位基因的存在也显著增加了RPL的风险(比值比1.63,95%可信区间1.16 - 2.29,p = 0.004)。按种族分层的荟萃分析表明,在亚洲人群中,使用固定模型时,携带等位基因2的个体RPL风险增加(比值比1.29,95%可信区间1.04 - 1.61,p = 0.01)。然而,本研究的数据清楚地表明,IL1RN VNTR多态性是研究人群中妊娠丢失的遗传危险因素。