The Role Of Semaphorin 7A In Alternatively Activation Of Macrophages

S D A Y 854 Sequencing Of The ST2 Gene and The Identification Of Genetic Determinants Of Serum Total ST2 Levels: Strong Evidence For Replication Across European and African American Populations Dr. Rasika A. Mathias, ScD, Lili Huang, MPH, Dr. Candelaria I. Vergara, MD, PhD, Dr. Li Gao, MD, PhD, Nicholas M. Rafaels, Joseph Potee, Mrs. Monica Campbell, Dr. Hironori Masuko, MD, PhD, Justyna Fert-Bober, James Snider, Dr. Margaret Taub, PhD, Dr. Ingo Ruczinski, PhD, Dr. Terri H. Beaty, PhD, Dr. Jennifer E. Van Eyk, PhD, Dr. Kathleen C. Barnes, PhD, FAAAAI; Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD, Department of Medicine, Johns Hopkins University, Baltimore, MD, Critical Diagnostics, San Diego, CA, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD. RATIONALE: ST2 (IL1RL1), in its soluble form (sST2) neutralizes its ligand, IL-33, by acting as a decoy receptor. Serum sST2 has been used as a biomarker for disease severity and outcome for multiple inflammatory and lung diseases, including atopic asthma. We previously showed a 10-SNP haplotype as a key determinant of serum sST2 levels in targeted deep resequencing studies of ST2 in 241 samples of African ancestry (p50.0002). METHODS: Serum sST2 was measured by ELISA on an additional 440 African American and 196 European American samples. Four SNPs selected from the 10-SNP haplotype were genotyped using the ABI Taqman assay. Single-variant tests for the common variants were performed separately by race using the linear regression models assuming additive effects of alleles on log serum total ST2 adjusted for age, gender, asthma, batch, study and principal components to adjust for admixture. RESULTS: All four SNPs were significantly replicated (p<0.05) in the independent African American sample. Three of the four SNPs were strongly associated with sST2 levels in the European American samples (p<10). Importantly, predicted allelic effects were almost identical between the racial groups. CONCLUSIONS: We confirmed association between sST2 levels and SNPs in a previously identified ST2 haplotype in an independent sample of 440 African Americans, and replicated this association in a European American population with identical allelic effects. Two SNPs were predicted to be in a region with minimal binding evidence for Polymerase (RNA) II (DNA Directed) Polypeptide A (POLR2A) which is a DNAdependent RNA polymerase catalyzing transcription of DNA into RNA.