Salem Hagit, Yatchenko Yekaterina, Anosov Mariana, Rosenfeld Talya, Altarescu Gheona, Grisaru-Granovsky Sorina, Birk Ruth
Department of Nutrition, Faculty of Health Sciences, Ariel University, Israel.
Department of Nutrition, Faculty of Health Sciences, Ariel University, Israel; Genetics Unit and Department of Obstetrics & Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel.
Gene. 2018 Apr 5;649:58-62. doi: 10.1016/j.gene.2018.01.097. Epub 2018 Jan 31.
Irisin is a novel secreted myokine, encoded by the fibronectin type III domain-containing protein 5 (FNDC5) precursor gene. Irisin plays a role in the female reproductive system in pregnancy and in embryonic development, and is associated with fetal size. It is expressed in the ovary, placenta and neonatal cord serum. We studied whether maternal and neonatal FNDC5 genetic polymorphisms are associated with preterm birth (PTB). Blood for DNA analysis was collected from Israeli mothers (n = 315) and from umbilical veins of their respected idiopathic preterm (24-36 weeks) and control term (>37 weeks) newborns (n = 161). Genotypes of maternal and neonatal FNDC5 polymorphisms (rs726344 and rs1746661) were determined by restriction fragment length polymorphism analysis. Genotype-phenotype associations were analyzed using SPSS program. The Frequency of FNCD5 rs726344 G alleles in the Israeli cohort is 82%. We found significant FNCD5 rs726344 genotype frequencies control and PTB groups. Women bearing the FNDC5 rs726344 GG genotype had 2.18 fold ([CI] 1.193-4.008, p = 0.01) higher chance to deliver at term compared to both AG and AA genotypes (adjusting to age, gravidity, parity, weight percentile per gestational age and gender of newborn). Neonates carrying the FNDC5 rs726344 GG genotype had 2.24 fold ([CI] 0.979-5.134, p = 0.05) higher chance to be born at term compared to either AG or AA genotypes (adjusting to parity, previous abortions and weight percentile per gestational age). There was no significant association of the rs1746661 polymorphism with PTB. Thus, we determined FNDC5 polymorphisms frequencies in the Israeli population and demonstrated that maternal and neonatal FNDC5 rs726344 polymorphism is significantly associated with increased risk for PTB.
鸢尾素是一种新型分泌性肌动蛋白，由含纤连蛋白III结构域蛋白5（FNDC5）前体基因编码。鸢尾素在妊娠和胚胎发育的女性生殖系统中发挥作用，并与胎儿大小有关。它在卵巢、胎盘和新生儿脐带血清中表达。我们研究了母体和新生儿FNDC5基因多态性是否与早产（PTB）相关。从以色列母亲（n = 315）及其各自特发性早产（24 - 36周）和足月对照（> 37周）新生儿（n = 161）的脐静脉采集用于DNA分析的血液。通过限制性片段长度多态性分析确定母体和新生儿FNDC5多态性（rs726344和rs1746661）的基因型。使用SPSS程序分析基因型与表型的关联。以色列队列中FNCD5 rs726344 G等位基因的频率为82%。我们发现FNCD5 rs726344基因型频率在对照组和PTB组中有显著差异。与AG和AA基因型相比，携带FNDC5 rs726344 GG基因型的女性足月分娩的几率高出2.18倍（[CI] 1.193 - 4.008，p = 0.01）（调整年龄、孕次、产次、每孕周体重百分位数和新生儿性别）。与AG或AA基因型相比，携带FNDC5 rs726344 GG基因型的新生儿足月出生的几率高出2.24倍（[CI] 0.979 - 5.134，p = 0.05）（调整产次、既往流产史和每孕周体重百分位数）。rs1746661多态性与PTB无显著关联。因此，我们确定了以色列人群中FNDC5多态性的频率，并证明母体和新生儿FNDC5 rs726344多态性与PTB风险增加显著相关。
