Polymorphisms in the prostaglandin receptor EP2 gene confers susceptibility to tuberculosis.

OBJECTIVES: Prostaglandin E2 (PGE2) is an important lipid mediator of the inflammatory immune response during acute and chronic infections. PGE2 modulates a variety of immune functions via four receptors (EP1-EP4), which mediate distinct PGE2 effects. Mice lacking EP2 are more susceptible to infection by Mycobacterium tuberculosis (M.tb), have a higher bacterial load, and increase size and number of granulomatous lesions. Our aim was to assess whether single nucleotide polymorphisms (SNPs) in EP2 increase the risk of tuberculosis. METHODS: DNA re-sequencing revealed five common EP2 variants in the Chinese Han population. We sequenced the EP2 gene from 600 patients and 572 healthy controls to measure SNP frequencies in association with tuberculosis infections (TB) within the population. RESULTS: The rs937337 polymorphism is associated with increased risk to tuberculosis (p=0.0044, odds ratio [OR], 1.67; 95% confidential interval,1.22-2.27). The rs937337 AA genotype and the rs1042618 CC genotype were significantly associated with TB. An estimation of the frequencies of haplotypes revealed a single protective haplotype GACGC for tuberculosis (p=0.00096, odds ratio [OR], 0.56; 95% confidential interval, 0.41-0.77). Furthermore, we determined that the remaining SNPs of EP2 were nominally associated with clinical patterns of disease. CONCLUSIONS: We identified genetic polymorphisms in EP2 associated with susceptibility to tuberculosis within a Chinese population. Our data support that EP2 SNPs are genetic predispositions of increased susceptibility to TB and to different clinical patterns of disease.