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长链非编码RNA MALAT1 rs619586 G变异体降低复发性流产易感性

The lncRNA MALAT1 rs619586 G Variant Confers Decreased Susceptibility to Recurrent Miscarriage.

作者信息

Che Di, Yang Yanfang, Xu Yufen, Fang Zhenzhen, Pi Lei, Fu LanYan, Zhou Huazhong, Tan Yaqian, Lu Zhaoliang, Li Li, Liang Qihua, Xuan Qingshan, Gu Xiaoqiong

机构信息

Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Department of Prenatal Diagnosis, Maoming People's Hospital, Maoming, China.

出版信息

Front Physiol. 2019 Apr 9;10:385. doi: 10.3389/fphys.2019.00385. eCollection 2019.

Abstract

Cardiovascula disease and recurrent miscarriage have shared risk factors, and some cardiovascular disease-related candidate genes have been confirmed to be associated with recurrent miscarriage. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that is considered to be associated with susceptibility to cardiovascular disease. However, whether lncRNA MALAT1 polymorphisms are related to recurrent miscarriage susceptibility is unclear. We genotyped three lncRNA MALAT1 polymorphisms (rs591291, rs619586, and rs3200401) in 284 patients and 392 controls using TaqMan methods. Logistic regression was used to evaluate the odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age. Our results showed that the rs619586 G variant had protective effects against recurrent miscarriage (AG vs. AA: adjusted OR = 0.670, 95% CI = 0.457-0.982, = 0.040; GG vs. AA: adjusted OR = 0.278, 95% CI = 0.079-0.975, = 0.046; GG/AG vs. AA adjusted OR = 0.621, 95% CI = 0.429-0.900, = 0.012). In a combined analyses of protective genotypes, with regard to the three single nucleotide polymorphisms (SNPs), we found that individuals with two or three protective genotypes exhibited a significantly lower risk of recurrent miscarriage than those with no or only one protective genotype (adjusted OR = 0.369, 95% CI = 0.199-0.684, = 0.002). Moreover, the decrease in recurrent miscarriage risk with two or three protective genotypes was most pronounced in women less than 35 years of age (OR = 0.290, 95% CI = 0.142-0.589, < 0.001) and in women with 2-3 miscarriages (adjusted OR = 0.270, 95% CI = 0.126-0.580, < 0.001). In conclusion, our study suggests that the rs619586 G variant may have potential protective effects conferring a decreased risk of recurrent miscarriage in the southern Chinese population.

摘要

心血管疾病和复发性流产有共同的风险因素,一些与心血管疾病相关的候选基因已被证实与复发性流产有关。转移相关肺腺癌转录本1(MALAT1)是一种长链非编码RNA(lncRNA),被认为与心血管疾病易感性有关。然而,lncRNA MALAT1基因多态性是否与复发性流产易感性相关尚不清楚。我们采用TaqMan方法对284例患者和392例对照的3个lncRNA MALAT1基因多态性(rs591291、rs619586和rs3200401)进行基因分型。采用逻辑回归评估调整年龄后的比值比(OR)和95%置信区间(CI)。我们的结果显示,rs619586 G变异对复发性流产有保护作用(AG与AA:调整后OR = 0.670,95%CI = 0.457 - 0.982,P = 0.040;GG与AA:调整后OR = 0.278,95%CI = 0.079 - 0.975,P = 0.046;GG/AG与AA调整后OR = 0.621,95%CI = 0.429 - 0.900,P = 0.012)。在对三种单核苷酸多态性(SNP)的保护性基因型进行的综合分析中,我们发现具有两种或三种保护性基因型的个体复发性流产风险显著低于没有或只有一种保护性基因型的个体(调整后OR = 0.369,95%CI = 0.199 - 0.684,P = 0.002)。此外,具有两种或三种保护性基因型的复发性流产风险降低在35岁以下女性(OR = 0.290,95%CI = 0.142 - 0.589,P < 0.001)和有2 - 3次流产的女性中最为明显(调整后OR = 0.270,95%CI = 0.126 - 0.580,P < 0.001)。总之,我们的研究表明,rs619586 G变异可能具有潜在的保护作用,可降低中国南方人群复发性流产的风险。

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