Polymorphisms in Liver Receptor Homolog-1 and FSH Receptor is associated with Preterm Birth

KALUARACHCHI, DC; MOMANY, AM; BUSCH, T; GIMENEZ, LG; RYCKMAN, KK; COSENTINO, VR; SALEME, C; CHRISTENSEN, K; DAGLE, JM; MURRAY, JC

Vancouver

Congreso; Joint Meeting 2014, Pediatrics Academic Societies (PAS) and Asian Society For Pediatrics Research; 2014

Pediatric Academic Societies (PAS)

Background. Preterm birth (PTB), defined as a birth before 37 weeks gestation, is a major cause of neonatal mortality and morbidity. The etiology of PTB is multifactorial and there is strong evidence of genetic susceptibility, particularly on the maternal side. Because of the strong maternal component, some genetic studies have focused on maternal triads (mother and maternal grandparents). The aim of the study was to identify genetic variants contributing to preterm birth. Methods. We studied 24 SNPs in 4 candidate genes (NR5A2, FSHR, FOXP3, SERPINH1). SNPs were genotyped using Applied Biosystems Taqman probes and the Fluidigm genotyping platform. The SNPs genotyped for FSHR and SERPINH1 were chosen as they have previously been reported as significantly associated with preterm birth. The SNPs genotyped for FOXP3 and NR5A2 were selected using Haploview in order to get 80% coverage (MAF = 0.2) of the gene. Genotyping was completed on 669 maternal triads (mother and maternal grandparents of a preterm infant) from Denmark (141 triads), Argentina (358 triads), and the United States (170 triads). Data were analyzed using Family based association tests (FBAT). Results. Association with PTB was found in Liver Receptor Homolog-1 (NR5A2) and FSHR. In US maternal triads, 3 SNPs of NR5A2 gene (rs6658424, rs2737667 and rs 2821312) showed significant association (P<0.05). In Argentinian maternal triads, 3 SNPs of NR5A2 gene ( rs 12131233, rs 2690036 and rs10919806) and 2 SNPs of FSHR gene (rs 12473870 and rs 12473815) showed significant association (P<0.05). None of the SNPs showed significant association in Denmark maternal triads. Conclusions. This study suggests a genetic association between PTB and Liver Receptor Homolog-1 and FSH Receptor. These findings may have implications in further understanding the pathophysiology of PTB.