孕期母亲饮酒与儿童发育：乙醇脱氢酶1B（ADH1B）和乙醛脱氢酶2（ALDH2）基因多态性的作用——日本环境与儿童研究山梨附属研究
Maternal alcohol consumption during pregnancy and child development: Role of ADH1B and ALDH2 gene polymorphisms-The Yamanashi Adjunct Study of the Japan Environment and Children's Study.
作者信息
Miyake Kunio, Otawa Sanae, Kushima Megumi, Yui Hideki, Shinohara Ryoji, Horiuchi Sayaka, Akiyama Yuka, Ooka Tadao, Kojima Reiji, Yokomichi Hiroshi, Yamagata Zentaro
机构信息
Department of Epidemiology and Environmental Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Japan.
Center for Birth Cohort Studies, University of Yamanashi, Chuo, Japan.
出版信息
Alcohol Clin Exp Res (Hoboken). 2025 Jan;49(1):117-127. doi: 10.1111/acer.15487. Epub 2024 Nov 13.
BACKGROUND
The role of polymorphisms in genes regulating alcohol metabolism, particularly those modulating the impact of prenatal alcohol exposure on the neurodevelopment of offspring, remains inconclusive. Herein, we aimed to determine the involvement of ADH1B and ALDH2 gene polymorphisms in maternal alcohol consumption during pregnancy and the risk of developmental delay in offspring in a Japanese population.
METHODS
We analyzed 1727 mother-child pairs from the Yamanashi Adjunct Study of the Japan Environment and Children's Study. Maternal alcohol consumption during pregnancy was determined through a mid-pregnancy questionnaire and categorized into three groups: never-drinkers, those who quit drinking in early pregnancy, and current drinkers. Developmental delays in children were assessed in five domains using the Japanese version of the Ages and Stages Questionnaire, Third Edition (J-ASQ-3) at 3 years of age. We conducted a logistic regression analysis to explore the relationship between maternal drinking status during pregnancy and developmental delays in offspring with respect to maternal ADH1B (rs1229984) or ALDH2 (rs671) gene polymorphisms.
RESULTS
Children born to mothers who continued alcohol consumption during pregnancy had a higher risk of delayed communication skills at 3 years of age compared with children born to mothers who did not drink alcohol (adjusted odds ratio [OR], 5.82; 95% confidence interval, 1.84-18.38). Analysis by ALDH2 gene polymorphism revealed that alcohol consumption by mothers carrying the wild-type ALDH2 (*1/*1) increased the risk of delayed communication skills at 3 years of age, whereas alcohol consumption by mothers carrying a heterozygotic genotype of ALDH2 (*1/*2) enhanced the risk of developmental delay in all five domains of the J-ASQ-3. The impact of ADH1B gene polymorphism could not be clearly elucidated.
CONCLUSIONS
Our results suggest that alcohol consumption by pregnant females carrying the deficient variant ALDH2*2 genotype may increase the risk of developmental delay in their offspring.
背景
基因多态性在调节酒精代谢中的作用，尤其是那些调节产前酒精暴露对后代神经发育影响的基因多态性，目前尚无定论。在此，我们旨在确定乙醇脱氢酶1B（ADH1B）和乙醛脱氢酶2（ALDH2）基因多态性与日本人群孕期母亲饮酒及后代发育迟缓风险之间的关系。
方法
我们分析了来自日本环境与儿童研究山梨附属研究中的1727对母婴。通过孕中期问卷确定孕期母亲的饮酒情况，并分为三组：从不饮酒者、孕早期戒酒者和当前饮酒者。在儿童3岁时，使用日本版的《年龄与发育进程问卷》第三版（J-ASQ-3）在五个领域评估儿童的发育迟缓情况。我们进行了逻辑回归分析，以探讨孕期母亲饮酒状况与后代发育迟缓之间的关系，同时考虑母亲的ADH1B（rs1229984）或ALDH2（rs671）基因多态性。
结果
与母亲不饮酒的儿童相比，孕期持续饮酒的母亲所生的儿童在3岁时出现沟通技能延迟的风险更高（调整后的优势比[OR]，5.82；95%置信区间，1.84 - 18.38）。通过ALDH2基因多态性分析发现，携带野生型ALDH2（*1/*1）的母亲饮酒会增加其孩子在3岁时沟通技能延迟的风险，而携带杂合基因型ALDH2（*1/*2）的母亲饮酒会增加J-ASQ-3所有五个领域发育迟缓的风险。ADH1B基因多态性的影响尚不能明确阐明。
结论
我们的结果表明，携带缺陷型ALDH2*2基因型的怀孕女性饮酒可能会增加其后代发育迟缓的风险。
Zotero 插件