Elias Dario, Gimenez Lucas, Poletta Fernando, Campaña Hebe, Gili Juan, Ratowiecki Julia, Pawluk Mariela, Rittler Monica, Santos Maria R, Uranga Rocio, Heisecke Silvina L, Cosentino Viviana, Saleme Cesar, Gadow Enrique, Krupitzki Hugo, Camelo Jorge S Lopez
Laboratorio de Epidemiología Genética Centro de Educación Médica e Investigaciones Clínicas-Consejo Nacional de Investigaciones Científicas y Técnicas (CEMIC-CONICET), Centro de Educación Médica e Investigaciones Clínicas-Consejo Nacional de Investigaciones Científicas y Técnicas (CEMIC-CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
Estudio Colaborativo Latino Americano de Malformaciones Congénitas, CEMIC-CONICET, Ciudad Autónoma de Buenos Aires, Argentina.
Pediatr Res. 2021 Sep;90(3):678-683. doi: 10.1038/s41390-020-01200-z. Epub 2020 Oct 18.
Preterm birth (PTB) is the leading cause of perinatal morbimortality worldwide. Genetic and environmental factors could raise PTB risk. The aim of this study was to analyze the contribution of the statistical interaction between genes and vaginal-urinary tract infections (VI-UTI) to the risk of PTB by clinical subtype.
Twenty-four SNPs were genotyped in 18 candidate genes from 352 fetal triads and 106 maternal triads. Statistical interactions were evaluated with conditional logistic regression models based on genotypic transmission/disequilibrium test.
In PTB-idiopathic subtype mothers exposed to UTI, fetal SNPs rs11686474 (FSHR), rs4458044 (CRHR1, allele G), rs883319 (KCNN3), and maternal SNP rs1882435 (COL4A3) showed a nominal significant increment in prematurity risk. In preterm premature rupture of membranes (PPROM), fetal SNP rs2277698 (TIMP2) showed a nominal significant risk increment. In mothers exposed to VI, fetal SNP rs5742612 (IGF1) in PTB-PPROM and maternal SNP rs4458044 (CRHR1, allele C) in spontaneous PTB showed nominal significant increment in prematurity risk.
Certain maternal and fetal genes linked to infectious/inflammatory and hormonal regulation processes increase prematurity risk according to clinical subtype when mothers are exposed to UTI or VI. These findings may help in the understanding of PTB etiology and PTB prevention.
Preterm birth is a major cause of perinatal morbimortality worldwide and its etiology remains unknown. This work provides evidence on the statistical interaction of six genes with gestational vaginal or urinary infections leading to the occurrence of preterm births. Statistical interactions vary according to infection type, genotype (maternal and fetal), and clinical subtype of prematurity. Certain maternal and fetal genetic variants of genes linked to infectious/inflammatory and hormonal regulation processes would increase the risk of prematurity according to clinical subtype and infection type. Our findings may help in the study of etiology of preterm birth and its prevention.
早产是全球围产期发病和死亡的主要原因。遗传和环境因素会增加早产风险。本研究的目的是通过临床亚型分析基因与阴道-尿道感染（VI-UTI）之间的统计相互作用对早产风险的影响。
对352个胎儿三联体和106个母亲三联体的18个候选基因中的24个单核苷酸多态性（SNP）进行基因分型。基于基因型传递/不平衡检验，使用条件逻辑回归模型评估统计相互作用。
在暴露于尿路感染的特发性早产亚型母亲中，胎儿SNP rs11686474（FSHR）、rs4458044（CRHR1，等位基因G）、rs883319（KCNN3）以及母亲SNP rs1882435（COL4A3）显示早产风险有显著增加。在胎膜早破早产（PPROM）中，胎儿SNP rs2277698（TIMP2）显示早产风险有显著增加。在暴露于VI的母亲中，PPROM型早产中的胎儿SNP rs5742612（IGF1）以及自发性早产中的母亲SNP rs4458044（CRHR1，等位基因C）显示早产风险有显著增加。
当母亲暴露于尿路感染或VI时，某些与感染/炎症和激素调节过程相关的母亲和胎儿基因，根据临床亚型会增加早产风险。这些发现可能有助于理解早产的病因和预防。
早产是全球围产期发病和死亡的主要原因，其病因仍然不明。这项工作提供了六个基因与妊娠期阴道或尿道感染之间的统计相互作用导致早产发生的证据。统计相互作用因感染类型、基因型（母亲和胎儿）以及早产的临床亚型而异。与感染/炎症和激素调节过程相关的某些母亲和胎儿基因变异，会根据临床亚型和感染类型增加早产风险。我们的发现可能有助于早产病因的研究及其预防。
