Genetic Analysis of the Promoter Region of the Serotonin Receptor 5HT2B and Its Contribution to Pulmonary Hypertension Syndrome in Broiler-Type Chicken

Pulmonary Arterial Hypertension (PAH) is a disease characterized by high pulmonary artery pressure and pulmonary vascular resistance accompanied with a vascular remodeling of small pulmonary arterioles. Ascites is a condition which occurs in broiler chickens as a result of pulmonary hypertension syndrome (PHS). Our group has been investigating the chicken as a medical animal model for human PAH. We identified a region on chromosome 9 associated with susceptibility to ascites that contains the serotonin receptor 5HT2B gene. Sequence analysis of the upstream promoter regions of 5HT2B revealed 15 single nucleotide polymorphisms (SNPs). A cluster of three SNPs were found to affect overlapping predicted transcription factor binding sites. These SNPs were analyzed in a collection of DNA samples obtained from several lines previously phenotyped for ascites susceptibility. Statistical analyses of the data support the association of particular genotypes/haplotypes of the 5HT2B gene with resistance to ascites especially in females. In summary, SNPlotype data for 5HT2B is consistent with this chromosomal region being a quantitative trait locus for ascites.  Future work will include using these SNPs  for marker assisted selection to reduce ascites incidence in chicken and examination of expression levels of HTR2B for specific alleles.