摘要
目的探讨脐带血中生长相关基因甲基化状态与婴幼儿期生长发育的相关性,了解婴幼儿生长发育迟缓的可能原因和机制.方法采用巢式病例对照的研究设计,选取2014年1月-2018年12月舟山妇幼保健院收治的50例生长发育迟缓婴幼儿为迟缓组,根据1:1的比例,以出生体质量、孕周、喂养方式和婴幼儿实际年龄4个变量匹配的50例发育正常婴幼儿为对照组.在分娩后立即采集脐带血,检测H19、IGF2R和IGF2基因的甲基化水平;在出生后第6、12、18、24个月4个时间点评价婴幼儿的生长发育情况.采用线性回归模型,分析子代身高和体质量与脐带血H19、IGF2R和IGF2基因甲基化水平的相关性.结果子代生长发育相对迟缓组脐带血H19基因1fr片段CG位点和5fr片段CG位点甲基化水平高于对照组,差异均有统计学意义(均P<0.05).H19基因2fr片段CHH位点甲基化水平低于对照组(P<0.05),其余位点甲基化水平差异均无统计学意义(P>0.05).整合H19、IGF2R和IGF2基因CG、CHG和CHH类型各片段后,H19基因CHH位点甲基化水平低于对照组,差异有统计学意义(P<0.05);其余位点甲基化水平差异均无统计学意义(均P>0.05).调整新生儿性别和喂养方式等混杂因素后,线性回归模型分析结果显示,子代6、12、18、24月龄身高、体质量与脐带血H19、IGF2R和IGF2基因甲基化水平的关联性差异均无统计学意义(P>0.05).结论H19基因高甲基化状态可能与子代生长发育相对迟缓相关,而IGF2R和IGF2基因甲基化水平与子代生长发育无明显的关系.
Objective To identify the association of gene methylation in cord blood with infant growth and development,and to explore the possiblemechanisms of growth retardation in infant.Methods A 1∶1 matched nested case-control study design was applied.A total of50 infants with growth retardation and 50 controls of infants with normal growth were matched by birthweight,gestational week,feeding type and children’s age in Maternal and Child Health Hospital of Zhoushan from January 2014 to December 2018.Cord blood was collected immediately after delivery and the level methylation of H19,IGF2 R and IGF2 genes was detected.The growth and development of infants was evaluated at the 6 th,12 th,18 th and 24 th month after birth.The linear regression model was used to analyze the association of methylation level of H19,IGF2 R,and IGF2 genes with height and weight of offspring.Results The methylation level of two fractions at CG sites of H19 gene(1 fr and 5 fr)in the growth retardation group was higher than that in the control group,and the difference was statistically significant(P<0.05).The methylation level of 2 fr at CHH site in the H19 gene was lower than that in the control group(P<0.05),however,there was no significant difference between two groups in other sites(P>0.05).After integrating the CG,CHG and CHH types of H19,IGF2 R and IGF2 genes,the methylation level of CHH site of H19 gene was lower than that of the control group(P<0.05),there was no significant difference between two groups in other sites(P>0.05).After adjustment for potential confounders,there was no significant association of the methylation level of H19,IGF2 R and IGF2 genes in cord blood with height and weight of 6,12,18,24 months of offspring at the 6 th,12 th,18 th and 24 th month after birth(P>0.05).Conclusion The hypermethylation of the H19 gene may be related to growth retardation of infant,but no significant association between the methylation level of IGF2 R and IGF2 genes and the growth and development of offspring was detected.
作者
王海燕
黄满仙
吴金华
毛亚飞
蒲柳艳
朱素娟
丁海燕
余运贤
WANG Hai-Yan;HUANG Man-Xian;WU Jin-Hua(Maternal and Child Health Hospital of Zhoushan,Zhejiang 316000,China)
出处
《中国妇幼保健》
CAS
2020年第11期2020-2025,共6页
Maternal and Child Health Care of China
基金
浙江省科技计划项目(2014C33243)
浙江省医药卫生科技计划项目(2013KYB273、2014KYA277)
舟山市科技计划项目(2013C31066)
舟山市医药卫生科技计划项目(2013G02、2014A03)。
作者简介
通讯作者:吴金华,E-mail:wjh964567@126.com。