母亲糖尿病及UCP2基因多态性与子代先天性心脏病关联的病例对照研究

罗柳, 黄鹏, 王婷婷, 赵丽娟, 叶子薇, 张森茂, 陈乐陶, 刁静怡, 李金琦, 李依寰, 秦家碧

中国当代儿科杂志 ›› 2020, Vol. 22 ›› Issue (10) : 1092-1099.

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中国当代儿科杂志 ›› 2020, Vol. 22 ›› Issue (10) : 1092-1099. DOI: 10.7499/j.issn.1008-8830.2004011
论著·临床研究

母亲糖尿病及UCP2基因多态性与子代先天性心脏病关联的病例对照研究

  • 罗柳1, 黄鹏2, 王婷婷1, 赵丽娟1, 叶子薇1, 张森茂1, 陈乐陶1, 刁静怡1, 李金琦1, 李依寰1, 秦家碧1
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Association of maternal diabetes mellitus and UCP2 gene polymorphisms with congenital heart disease in offspring: a case-control study

  • LUO Liu1, HUANG Peng2, WANG Ting-Ting1, ZHAO Li-Juan1, YE Zi-Wei1, ZHANG Sen-Mao1, CHEN Le-Tao1, DIAO Jing-Yi1, LI Jin-Qi1, LI Yi-Huan1, QIN Jia-Bi1
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摘要

目的 探讨母亲糖尿病、解偶联蛋白2基因(UCP2)多态性及两者的交互作用与子代先天性心脏病(CHD)的关系。方法 采用以医院为基础的病例对照研究,选择2018年3月至2019年8月在湖南省儿童医院确诊的464例单纯CHD患儿的母亲为病例组,选择同期住院、无先天畸形的504例患儿的母亲为对照组。通过问卷调查,收集相关暴露信息,同时采集母亲静脉血5 mL,用于UCP2基因多态性检测。采用多因素logistic回归分析探讨母亲糖尿病、UCP2基因多态性及两者交互作用与子代CHD的关联性。结果 多因素logistic回归分析显示,在控制混杂因素后,患有妊娠期糖尿病(OR=2.96,95% CI:1.57~5.59)、有妊娠期糖尿病史(OR=3.16,95% CI:1.59~6.28)和妊娠前患有糖尿病(OR=4.52,95% CI:2.41~8.50)均显著增加子代CHD的风险(P < 0.05)。母亲UCP2基因两个位点rs659366(T/C vs C/C:OR=1.49,95% CI:1.02~2.16;T/T vs C/C:OR=2.77,95% CI:1.67~4.62)和rs660339(A/A vs G/G:OR=2.19,95% CI:1.34~3.58)的多态性与子代CHD的风险存在关联(P < 0.05)。交互作用分析显示,UCP2基因两个位点(rs659366和rs660339)的多态性与母亲糖尿病在子代CHD发生中存在交互作用(P < 0.05)。结论 母亲糖尿病、UCP2基因多态性及其交互作用与子代CHD发病相关。

Abstract

Objective To study the association of maternal diabetes mellitus (DM), uncoupling protein 2 (UCP2) gene polymorphisms, and their interaction with the risk of congenital heart disease (CHD) in offspring. Methods A hospital-based case-control study was conducted. A total of 464 mothers of children with CHD alone who were diagnosed in Hunan Children's Hospital from March 2018 to August 2019 were enrolled as the case group. A total of 504 mothers of healthy children who were hospitalized during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect the information on exposure. Venous blood samples (5 mL) were collected from the mothers to detect UCP2 gene polymorphisms. A multivariate logistic regression analysis was used to investigate the association of maternal DM, UCP2 gene polymorphisms, and their interaction with CHD in offspring. Results After control for confounding factors, the multivariate logistic regression analysis showed that mothers with gestational DM (OR=2.96, 95%CI:1.57-5.59), a history of gestational DM (OR=3.16, 95%CI:1.59-6.28), and pregestational DM (OR=4.52, 95%CI:2.41-8.50) significantly increased the risk of CHD in offspring (P < 0.05). The polymorphisms of the UCP2 gene at rs659366 (T/C vs C/C:OR=1.49, 95%CI:1.02-2.16; T/T vs C/C:OR=2.77, 95%CI:1.67-4.62) and rs660339 (A/A vs G/G:OR=2.19, 95%CI:1.34-3.58) were significantly associated with risk of CHD in offspring (P < 0.05). The interaction analysis showed an interaction between the polymorphisms of the UCP2 gene at rs659366 and rs660339 and maternal DM in the development of CHD (P < 0.05). Conclusions Maternal DM, UCP2 gene polymorphisms, and their interaction are associated with the development of CHD in offspring.

关键词

先天性心脏病 / 糖尿病 / UCP2基因 / 病例对照研究 / 交互作用 / 子代

Key words

Congenital heart disease / Diabetes mellitus / UCP2 gene / Case-control study / Interaction / Offspring

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罗柳, 黄鹏, 王婷婷, 赵丽娟, 叶子薇, 张森茂, 陈乐陶, 刁静怡, 李金琦, 李依寰, 秦家碧. 母亲糖尿病及UCP2基因多态性与子代先天性心脏病关联的病例对照研究[J]. 中国当代儿科杂志. 2020, 22(10): 1092-1099 https://doi.org/10.7499/j.issn.1008-8830.2004011
LUO Liu, HUANG Peng, WANG Ting-Ting, ZHAO Li-Juan, YE Zi-Wei, ZHANG Sen-Mao, CHEN Le-Tao, DIAO Jing-Yi, LI Jin-Qi, LI Yi-Huan, QIN Jia-Bi. Association of maternal diabetes mellitus and UCP2 gene polymorphisms with congenital heart disease in offspring: a case-control study[J]. Chinese Journal of Contemporary Pediatrics. 2020, 22(10): 1092-1099 https://doi.org/10.7499/j.issn.1008-8830.2004011

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基金

国家自然科学基金项目(81803313);湖南省重点研发计划项目(2018SK2063);湖南省托举人才项目(2020TJ-N07);湖南省自然科学基金项目(2018JJ2551)。


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