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

GIMENEZ LG,; MOMANY AM,; GILI JA ,; POLETTA FA,; BUSCH, TAMARA D; COMAS B,; COSENTINO V,; SALEME C,; KRUPITZKI, H; CASTILLA EE,; GADOW EC; MURRAY JC; LOPEZ CAMELO JS

San Diego

Congreso; American Society of Human Genetics 64th Annual Meeting; 2014

American Society of Human Genetics

Background. Preterm birth (PTB) is the leading cause of perinatal morbidityand mortality worldwide. The etiology of PTB is multi-factorial, heterogeneous, and there is strong evidence of genetic susceptibility. The aim of thiswork was to investigate the association between 24 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 SNPs have been previously studied in a heterogeneous group of PTBs. Methods. The sample included 674 triads (proband,mother, father) recruited at the Nuestra Señora de la Merced MaternityHospital in Tucumán, Argentina. Of these triads, 233 had probands fromPTB-I, 241 had probands from PTB-PROM and 200 had probands fromPTB-M. We studied 24 SNPs in 18 candidate genes. Genotyping was performed using Applied Biosystems Taqman probes and the Fluidigm genotyping platform. SNPs were chosen based on previous reports of significantassociation with preterm birth. Data were analyzed using the TransmissionDisequilibrium Test (TDT) (Spielman et al. 1993). The p values (<0.05)were uncorrected for multiple comparisons. Preliminary results. We founda significant association (P<0.05) between a SNP in COL4A3 (rs10178458),a SNP in PON1 (rs2272365), and a SNP in CRHR1 (rs4458044) with PTBI. A SNP in F3 (rs610277) showed significant association (P<0.05) withPTB-PROM and PTB-M. A SNP in KCNN3 (rs883319) showed significantassociation (P<0.05) with PTB-M. Conclusions. This study suggests differentgenetic influences between the different clinical subtypes. These findingsmay have implications in understanding the pathophysiology of clinical subtypes of preterm birth