Dario Elias1,2, Lucas Gimenez1,2,3, Fernando Poletta1,2,3, Hebe Campaña1,2,4, Juan Gili1,2,5, Julia Ratowiecki1,2, Mariela Pawluk1,2, Monica Rittler1,2,6, Maria R Santos1,2,4,7, Rocio Uranga1,2,8, Silvina L Heisecke1, Viviana Cosentino1,2, Cesar Saleme9, Enrique Gadow1, Hugo Krupitzki1, Jorge S Lopez Camelo10,11,12. 1. 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. 2. Estudio Colaborativo Latino Americano de Malformaciones Congénitas, CEMIC-CONICET, Ciudad Autónoma de Buenos Aires, Argentina. 3. Instituto Nacional de Genética Médica Populacional, CEMIC-CONICET, Ciudad Autónoma de Buenos Aires, Argentina. 4. Comisión de Investigaciones Científicas, Buenos Aires, Argentina. 5. Instituto Académico Pedagógico de Ciencias Humanas, Universidad Nacional de Villa María, Córdoba, Argentina. 6. Hospital Materno Infantil Ramón Sarda, Buenos Aires, Argentina. 7. Instituto Multidisciplinario de Biología Celular, Buenos Aires, Argentina. 8. Hospital San Juan de Dios, Buenos Aires, Argentina. 9. Instituto de Maternidad y Ginecología Nuestra Señora de las Mercedes, Tucumán, Argentina. 10. 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. jslc@eclamc.org. 11. Estudio Colaborativo Latino Americano de Malformaciones Congénitas, CEMIC-CONICET, Ciudad Autónoma de Buenos Aires, Argentina. jslc@eclamc.org. 12. Instituto Nacional de Genética Médica Populacional, CEMIC-CONICET, Ciudad Autónoma de Buenos Aires, Argentina. jslc@eclamc.org.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT: 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.
Authors: Hugo B Krupitzki; Enrique C Gadow; Juan A Gili; Belén Comas; Viviana R Cosentino; César Saleme; Jeffrey C Murray; Jorge S Lopez Camelo Journal: Am J Perinatol Date: 2012-11-06 Impact factor: 1.862
Authors: Dario E Elias; Maria R Santos; Hebe Campaña; Fernando A Poletta; Silvina L Heisecke; Juan A Gili; Julia Ratowiecki; Viviana Cosentino; Rocio Uranga; Diana Rojas Málaga; Alice Brinckmann Oliveira Netto; Ana Carolina Brusius-Facchin; César Saleme; Mónica Rittler; Hugo B Krupitzki; Jorge S Lopez Camelo; Lucas G Gimenez Journal: J Community Genet Date: 2022-08-17
Authors: Jelonia T Rumph; Victoria R Stephens; Joanie L Martin; LaKendria K Brown; Portia L Thomas; Ayorinde Cooley; Kevin G Osteen; Kaylon L Bruner-Tran Journal: Int J Environ Res Public Health Date: 2022-01-23 Impact factor: 3.390