Association of candidate gene single nucleotide polymorphisms with the clinical subtypes of preterm birth (PTB)

GIMENEZ, LG; MOMANY, AM; GILI, JA; POLETTA, FA; BUSCH, T; COMAS, B; COSENTINO, VR; SALEME, C; KRUPITZKI, HB; CASTILLA, E; GADOW, EG; MURRAY, JC; LOPEZ CAMELO, JS

San Diego, CA

Congreso; Annual Meeting American Society of Human Genetics; 2014

The American Society Human Genetics (ASHG)

Background. Preterm birth (PTB) is the leading cause of perinatal morbidity and mortalityworldwide. The etiology of PTB is multi-factorial, heterogeneous, and there is strong evidence of genetic susceptibility. The aim of this work was to investigate the association between24 single nucleotide polymorphism (SNPs) and the different clinical subtypes of preterm birth: spontaneous (PTB-I), premature rupture of membrane (PTB-PROM) and medicallyindicated (PTB-M).These SNPshave been previously studied in a heterogeneous group of PTBs. Methods. The sample included 674 triads (proband, mother, father) recruited at the NuestraSeñora de la Merced Maternity Hospital in Tucumán, Argentina. Of these triads, 233 had probands from PTB-I, 241 had probands from PTB-PROM and 200 had probands from PTB-M. We studied 24 SNPs in 18 candidate genes. Genotyping was performed using Applied BiosystemsTaqman probes and the Fluidigm genotyping platform. SNPswere chosen based on previous reports of significant association with preterm birth. Data were analyzed using the Transmission Disequilibrium Test (TDT)(Spielman et al. 1993). The p values (<0.05)were uncorrected for multiple comparisons. Preliminary results. We found a significant association (P<0.05) betweena SNP in COL4A3(rs10178458), a SNP inPON1 (rs2272365), and a SNP inCRHR1 (rs4458044) with PTB-I. A SNP inF3 (rs610277) showed significant association (P<0.05) with PTB-PROM and PTB-M.A SNP inKCNN3 (rs883319)showed significant association (P<0.05) with PTB-M. Conclusions. This study suggests different genetic influences between the different clinical subtypes. These findings may have implications in understanding the pathophysiology of clinical subtypes of preterm birth.