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29.08.2020 | Original Communication

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

verfasst von: Juan Zhang, Mei-Jiao Chen, Gui-Xian Zhao, Hong-Fu Li, Lei Wu, Yong-Feng Xu, Yajin Liao, Zengqiang Yuan, Zhi-Ying Wu

Erschienen in: Journal of Neurology | Ausgabe 2/2021

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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 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.

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Papadopoulos MC, Bennett JL, Verkman AS (2014) Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol 10:493–506. https://doi.org/10.1038/nrneurol.2014.141CrossRefPubMedPubMedCentral

Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG (2007) The spectrum of neuromyelitis optica. Lancet Neurol 6:805–815. https://doi.org/10.1016/S1474-4422(07)70216-8CrossRefPubMed

Reich DS, Lucchinetti CF, Calabresi PA (2018) Multiple Sclerosis. N Engl J Med 378:169–180. https://doi.org/10.1056/NEJMra1401483CrossRefPubMedPubMedCentral

Willer CJ, Dyment DA, Risch NJ, Sadovnick AD, Ebers GC, Canadian Collaborative Study Group (2003) Twin concordance and sibling recurrence rates in multiple sclerosis. Proc Natl Acad Sci 100:12877–12882. https://doi.org/10.1073/pnas.1932604100CrossRefPubMedPubMedCentral

Ebers GC, Sadovnick AD, Risch NJ (1995) A genetic basis for familial aggregation in multiple sclerosis. Nature 377:150–151. https://doi.org/10.1038/377150a0CrossRefPubMed

Matiello M, Kim HJ, Kim W et al (2010) Familial neuromyelitis optica. Neurology 75:310–315. https://doi.org/10.1212/WNL.0b013e3181ea9f15CrossRefPubMedPubMedCentral

The MHC sequencing consortium (1999) Complete sequence and gene map of a human major histocompatibility complex. Nature 401:921–923. https://doi.org/10.1038/44853CrossRef

Lessard CJ, Ice JA, Adrianto I et al (2012) The genomics of autoimmune disease in the era of genome-wide association studies and beyond. Autoimmun Rev 11:267–275. https://doi.org/10.1016/j.autrev.2011.10.003CrossRefPubMed

Campbell RD, Trowsdale L (1993) Map of the human MHC. Immunol Today 14:349–352. https://doi.org/10.1016/0167-5699(93)90234-CCrossRefPubMed

10.

Ogawa K, Okuno T, Hosomichi K et al (2019) Next-generation sequencing identifies contribution of both class I and II HLA genes on susceptibility of multiple sclerosis in Japanese. J Ne-uroinflammation 16:162. https://doi.org/10.1186/s12974-019-1551-zCrossRef

11.

Wang H, Dai Y, Qiu W et al (2011) HLA-DPB1 0501 is associated with susceptibility to anti-aquaporin-4 antibodies positive neuromyelitis optica in southern Han Chinese. J Neuroimmunol 233:181–184. https://doi.org/10.1016/j.jneuroim.2010.11.004CrossRefPubMed

12.

Estrada K, Whelan CW, Zhao F et al (2018) A whole-genome sequence study identifies geneti-c risk factors for neuromyelitis optica. Nat Commun 9:1929. https://doi.org/10.1038/s41467-018-04332-3CrossRefPubMedPubMedCentral

13.

Terao C, Brynedal B, Chen Z et al (2019) Distinct HLA associations with rheumatoid arthritis subsets defined by serological subphenotype. Am J Hum Genet 105:616–624. https://doi.org/10.1016/j.ajhg.2019.08.002CrossRefPubMedPubMedCentral

14.

Diakite M, Clark TG, Auburn S et al (2009) A genetic association study in the Gambia using tagging polymorphisms in the major histocompatibility complex class III region implicates a HLA-B associated transcript 2 polymorphism in severe malaria susceptibility. Hum Genet 125:105–109. https://doi.org/10.1007/s00439-008-0597-2CrossRefPubMed

15.

Singal DP, Li J, Zhu Y (2000) HLA class III region and susceptibility to rheumatoid arthritis. Clin Exp Rheumatol 18:485–491PubMed

16.

Tarassi K, Carthy D, Papasteriades C et al (1998) HLA-TNF haplotype heterogeneity in Greek SLE patients. Clin Exp Rheumatol 16:66–68PubMed

17.

Ratanachaiyavong S, Demaine AG, Campbell RD, McGregor AM (1991) Heat shock protein 70 (HSP70) and complement C4 genotypes in patients with hyperthyroid Graves’s disease. Clin Exp Immunol 84:48–52PubMedPubMedCentral

18.

Singal DP, Li J, Zhu Y (1999) Genetic basis for rheumatoid arthritis. Arch Immunol Ther Exp 47:307–311

19.

Singal DP, Li J, Lei K (1999) Genetics of rheumatoid arthritis (RA): two separate regions in the major histocompatibility complex contribute to susceptibility to RA. Immunol Lett 69:301–306. https://doi.org/10.1016/s0165-2478(99)00108-xCrossRefPubMed

20.

Wu R, Li A, Sun B et al (2019) A novel m6A reader Prrc2a controls oligodendroglial specification and myelination. Cell Res 29:23–41. https://doi.org/10.1038/s41422-018-0113-8CrossRefPubMed

21.

Wingerchuk DM, Banwell B, Bennett JL et al (2015) International consensus diagnostic criteri-a for neuromyelitis optica spectrum disorders. Neurology 85:177–189. https://doi.org/10.1212/WNL.0000000000001729CrossRefPubMedPubMedCentral

22.

Thompson AJ, Banwell BL, Barkhof F et al (2018) Diagnosis of multiple sclerosis: 2017 revisions of the McDonald Criteria. Lancet Neurol 17:162–173. https://doi.org/10.1016/S1474-4422(17)30470-2CrossRefPubMed

23.

Piras IS, Angius A, Andreani M et al (2014) BAT2 and BAT3 polymorphisms as a novel genetic risk factors for rejection after HLA-related SCT. Bone Marrow Transplant 49:1400–1404. https://doi.org/10.1038/bmt.2014.177CrossRefPubMedPubMedCentral

24.

Yoshimura S, Isobe N, Matsushita T et al (2013) Distinct genetic and infectious profiles in Ja-panese neuromyelitis optica patients according to anti-aquaporin 4 antibody status. J Neurol Neurosurg Psychiatry 84:29–34. https://doi.org/10.1136/jnnp-2012-302925CrossRefPubMed

25.

Hafler DA, Compston A, International Multiple Sclerosis Genetics Consortium et al (2007) Ris-k alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 357:851–862. https://doi.org/10.1056/NEJMoa073493CrossRefPubMed

26.

Dyment DA, Ebers GC, Sadovnick AD (2004) Genetics of multiple sclerosis. Lancet Neurol 3:104–110. https://doi.org/10.1016/s1474-4422(03)00663-xCrossRefPubMed

27.

Patsopoulos NA, Bayer Pharma MS Genetics Working Group, Steering Committees of Studies Evaluating IFNβ-1b, and CCR1-Antagonist et al (2011) Genome-wide meta-analysis identifies n-ovel multiple sclerosis susceptibility loci. Ann Neurol 70:897–912. https://doi.org/10.1002/ana.22609CrossRefPubMedPubMedCentral

28.

Yamasaki K, Horiuchi I, Minohara M et al (1999) HLA-DPB1*0501-associated opticospinal m-ultiple sclerosis: clinical, neuroimaging and immunogenetic studies. Brain 122:1689–1696. https://doi.org/10.1093/brain/122.9.1689CrossRefPubMed

29.

Liu QB, Li ZX, Zhao GX, Yu H, Wu ZY (2014) No association between identified multiple sclerosis non-MHC risk loci and neuromyelitis optica. Neurosci Bull 30:1036–1044. https://doi.org/10.1007/s12264-013-1457-1CrossRefPubMedPubMedCentral

Titel: Common genetic variants in PRRC2A are associated with both neuromyelitis optica spectrum disorder and multiple sclerosis in Han Chinese population
verfasst von: Juan Zhang
Mei-Jiao Chen
Gui-Xian Zhao
Hong-Fu Li
Lei Wu
Yong-Feng Xu
Yajin Liao
Zengqiang Yuan
Zhi-Ying Wu
Publikationsdatum: 29.08.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology / Ausgabe 2/2021
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-020-10184-z

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