Common genetic variants in PRRC2A are associated with both neuromyelitis optica spectrum disorder and multiple sclerosis in Han Chinese population

Background: The proline-rich coiled-coil 2A (PRRC2A) gene has been reported to underlie risk of various autoimmune diseases. However, no data reveal the risk susceptibility of PRRC2A to neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) so far.

Objectives: To explore the association between PRRC2A variants and NMOSD and MS susceptibility in Han Chinese population.

Methods: Totally, 207 NMOSD (98 AQP4⁺ and 109 AQP4^-) patients, 141 MS and 196 healthy controls (HC) were enrolled. Candidate tagging single nucleotide polymorphisms (tag-SNPs) were selected from the 1000G database based on the Chinese data. SNP genotyping was performed using MassArray and Sanger sequencing.

Results: PRRC2A variants rs2736171, rs2736157, rs2844470 alter susceptibility to AQP4⁺ NMOSD, while rs2242659 to MS. Genotype AT of rs2844470 and AG of rs2242659 increased risk susceptibility for AQP4⁺ NMOSD and MS, respectively. AQP4⁺ NMOSD exhibited a higher frequency of genotype AG of rs2736157 compared with AQP4^- NMOSD. Haplotype TCAAGGTAG was conferred risk susceptibility to AQP4⁺ NMOSD and haplotype TTAGAGTAG had a protective effect on both AQP4⁺ and AQP4^- NMOSD. Further, we identified various gene expression levels in disease-related regions that are significantly modulated by three cis-eQTL SNPs rs2736157, rs2736171 and rs2242659 (p < 1.05 × 10^-4).

Conclusions: PRRC2A variants are first reported to be associated with NMOSD and MS. The identified PRRC2A variants may shed light on the pathogenesis of NMOSD and MS and potentially lead to an individualized therapeutic approach for both distinct disease entities.

Keywords: Chinese; Multiple sclerosis; Neuromyelitis optica spectrum disorder; PRRC2A.