Rosenfeld Talya, Salem Hagit, Altarescu Gheona, Grisaru-Granovsky Sorina, Tevet Aharon, Birk Ruth
Department of Nutrition, School of Health Sciences, Ariel University, Ariel, Israel.
Genetics Unit and Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel.
Arch Gynecol Obstet. 2017 Aug;296(2):215-222. doi: 10.1007/s00404-017-4412-y. Epub 2017 Jun 13.
Preterm birth (PTB) is a complex trait with strong genetic background, whose etiology is not fully understood. It was recently suggested that pregnancy duration is affected by fetal genetic variation even more than by the maternal genome. Vitamin D receptor (VDR) is involved in embryonic implantation and fertility. We studied the association between both maternal and neonatal vitamin D receptor (VDR) genetic variation and PTB.
Maternal and fetal (umbilical cord) DNA was isolated from Jewish Israeli idiopathic preterm newborns (24-36 weeks, n = 146) and control term newborns (>37 weeks, n = 229). Maternal and fetal VDR polymorphisms (FokI, ApaI, BsmI, TaqI) were analyzed by restriction fragment length polymorphism analysis. Using SPSS analysis to correlate VDR genotypes with phenotypic variation: pregnancy duration, preterm birth and spontaneous miscarriages, adjusted for gravidity, parity and gender of newborn.
Women homozygous to VDR ApaI (AA) genotype had significant twofold increase risk for PTB [OR 1.973, (CI) 1.183-3.289, p = 0.009] compared to heterozygous women. Male newborns had significant (p < 0.05) 1.73-fold increase of PTB. Women with history of previous (≥1) spontaneous miscarriage had a significant increased risk for PTB if their newborn carried either of the VDR BsmI homozygous (BB or bb) genotypes compared to the heterozygous (Bb) genotype [OR 6.857, (CI) 1.273-36.934, p = 0.018 and OR 9.231, (CI) 1.753-48.618, p = 0.008, respectively], or VDR ApaI homozygous (AA or aa) genotype compared to heterozygous (Aa) genotype [OR 4.33, (CI) 1.029-18.257, p = 0.046 and OR 7.2, (CI) 1.34-38.917, p = 0.021, respectively].
We show association between maternal and fetal VDR genotype variants with PTB.
早产（PTB）是一种具有强大遗传背景的复杂性状，其病因尚未完全明确。最近有研究表明，孕期时长受胎儿基因变异的影响甚至超过母体基因组。维生素D受体（VDR）参与胚胎着床和生育过程。我们研究了母体和新生儿维生素D受体（VDR）基因变异与早产之间的关联。
从以色列犹太裔特发性早产新生儿（24 - 36周，n = 146）和足月对照新生儿（>37周，n = 229）中分离出母体和胎儿（脐带）DNA。通过限制性片段长度多态性分析来检测母体和胎儿VDR基因多态性（FokI、ApaI、BsmI、TaqI）。使用SPSS分析将VDR基因型与表型变异（孕期时长、早产和自然流产）进行关联分析，并对孕妇的妊娠次数、产次和新生儿性别进行校正。
与杂合子女性相比，VDR ApaI基因型纯合子（AA）的女性发生早产的风险显著增加两倍[比值比（OR）1.973，置信区间（CI）1.183 - 3.289，p = 0.009]。男性新生儿早产的发生率显著增加（p < 0.05），为1.73倍。既往有≥1次自然流产史的女性，如果其新生儿携带VDR BsmI纯合子（BB或bb）基因型，与杂合子（Bb）基因型相比，发生早产的风险显著增加[分别为OR 6.857，CI 1.273 - 36.934，p = 0.018和OR 9.231，CI 1.753 - 48.618，p = 0.008]；或者携带VDR ApaI纯合子（AA或aa）基因型，与杂合子（Aa）基因型相比，发生早产的风险也显著增加[分别为OR 4.33，CI 1.029 - 18.257，p = 0.046和OR 7.2，CI 1.34 - 38.917，p = 0.021]。
我们发现母体和胎儿VDR基因型变异与早产之间存在关联。
