Common genetic variants in PRRC2A are associated with both neuromyelitis optica spectrum disorder and multiple sclerosis
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ORIGINAL COMMUNICATION
Common genetic variants in PRRC2A are associated with both neuromyelitis optica spectrum disorder and multiple sclerosis in Han Chinese population Juan Zhang1 · Mei‑Jiao Chen1 · Gui‑Xian Zhao2,3 · Hong‑Fu Li1 · Lei Wu1 · Yong‑Feng Xu1 · Yajin Liao4 · Zengqiang Yuan4 · Zhi‑Ying Wu1 Received: 13 June 2020 / Revised: 19 August 2020 / Accepted: 24 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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 A QP4+ and 109 A QP4−) 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 A QP4− NMOSD. Haplotype + TCAAGGTAG was conferred risk susceptibility to A QP4 NMOSD and haplotype TTAGAGTAG had a protective effect on both AQP4+ and A QP4− 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 0.05).
in the codominant, dominant, overdominant and additive model (Table 2). No statistically significant associations were detected when comparing was conducted between AQP4− NMOSD and HC (Supplemental Table S3). As listed in Table 3, the frequency of the genotype AG of rs2736157 variant in NMOSD patients was significantly higher in patients with AQP4+ status in comparison with those with AQP4− status (OR [95% CI] 0.53 [0.28–0.99], dominant model and OR [95% CI] 0.50 [0.26–0.94], overdominant model, respectively). When comparisons were made between MS and HC, we observed the PRRC2A gene variant rs2242659 alters MS susceptibility in codominant, dominant, overdominant and additive model (Table 4).
Haplotype analysis between NMOSD (AQP4+ and AQP4−), MS patients and health controls As displayed in Fig. 2a, the haplotype TCAAGGTAG was found to be a risk factor for A QP4+ NMOSD patients, since its frequency in patients with A QP4+ status was significantly higher than HC (14.8% versus 8.2%). Compared with the control group, the frequency distribution of the haplotype TTAGAGTAG was significantly decreased in both A QP4+ − and AQP4 group, suggesting haplotype TTAGAGTAG was protective for both AQP4+ and AQP4
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