Promoter SNPs in the Serotonin Receptor Gene 5HT2B and Their Association with Ascites in Chicken

5-Hydroxytryptamine receptor 2B (5HT_2B) is a member of the 5-HT₂ receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) and mediates many of the central and peripheral physiologic functions of 5-HT. Previous studies suggest that 5HT_2B plays a key role in pulmonary vasoconstriction and pulmonary artery smooth muscle cell proliferation in chickens developing ascites. Ascites is a condition which occurs in broiler chickens as a result of elevated pulmonary vascular pressure and ventricular hypertrophy; ultimately leading to heart failure and death. Our group has been investigating the chicken as an animal model for a related condition in humans, idiopathic pulmonary arterial hypertension (IPAH). A genome-wide association study identified a region on chromosome 9 associated with susceptibility to ascites that contains the serotonin receptor 5HT_2B gene. Sequence analysis of the upstream promoter region of 5HT2B revealed 15 single nucleotide polymorphisms (SNPs). Some of these SNPs were found to affect potential binding sites for transcription factors. We SNPlotyped a collection of DNA samples from several broiler 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. Future work will include using these SNPs for marker assisted selection to reduce ascites incidence in chicken and examination of 5HT2B gene expression levels for specific alleles.