Formyl peptide receptor 1 (FPR1) is a class A G protein-coupled receptor. When stimulated by chemoattractants, such as formyl peptides released by bacteria or certain virus-derived proteins, it leads to neutrophil chemotaxis, degranulation and superoxide production. These activities are essential to the elimination of invading pathogens and damaged tissues suggesting that FPR1 plays an important role in the innate immune system.

Using pharmacogenomics approaches, scientists at the National Center for Drug Screening/Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Fudan University and Shanghai Jiaotong University investigated five FPR1 single nucleotide polymorphisms (SNPs) across 209 healthy Han Chinese to map the distribution of FPR1 haplotypes. In some cases the allele frequencies found differed from those reported in other races and from those documented for Han Chinese in the HapMap. Then, they stably transfected CHO-Gα16 cells with cDNAs encoding the twelve most frequent FPR1 Han Chinese haplotypes, and discovered the pharmacological consequences of these variants using fNle-Leu-Phe-Nle-Tyr-Lys-fluorescein to study receptor binding affinity. They identified the V101L FPR1 polymorphism as having greater receptor pKi for cyclosporins and enhanced downstream antagonistic activity including calcium mobilisation, MAPK phosphorylation and chemotaxis. Based on these results, it is suggested that in patients carrying the V101L FPR1 polymorphism, cyclosporin A may cause over-suppression of FPR1 activity and therefore unexpected clinical effects.

This work, carried out by the research team led by Professor Ming-Wei Wang,  took four years to complete and received the financial support from the National Mega Program on Drug Discovery. It was published online recently at Biochemical Journal (http://www.biochemj.org/bj/imps/abs/BJ20121839.htm). "This paper is a good example of combining a pharmacogenomics study with follow-on laboratory experiments to test hypotheses raised by the pharmacogenomics work", commented by an editor of the journal.