Whole-Genome Analysis in Korean Patients with Autoimmune Myasthenia Gravis
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: The underlying cause of myasthenia gravis (MG) is unknown, although it likely involves a genetic component. However, no common genetic variants have been unequivocally linked to autoimmune MG. We sought to identify the genetic variants associated with an increased or decreased risk of developing MG in samplesfrom a Korean Multicenter MG Cohort. Materials and Methods: To determinenew genetic targets related to autoimmune MG, a whole genome-based single nucleotide polymorphisms (SNP) analysis was conducted using an AxiomTM Genome-Wide ASI 1 Array, comprising 598375 SNPs and samples from 109 MG patientsand 150 neurologically normal controls. Results: In total, 641 SNPs from five case-control associations showed p-values of less than 10-5. From regional analysis, we selected seven candidate genes (RYR3, CACNA1S, SLAMF1, SOX5, FHOD3, GABRB1, and SACS) for further analysis. Conclusion: The present study suggests that a few genetic polymorphisms, such as in RYR3, CACNA1S, and SLAMF1, might be related to autoimmune MG. Our findings also encourage furtherstudies, particularly confirmatory studies with larger samples, to validate and analyze the association between these SNPs and autoimmune MG.
Abstract
Purpose: The underlying cause of myasthenia gravis (MG) is unknown, although it likely involves a genetic component. However, no common genetic variants have been unequivocally linked to autoimmune MG. We sought to identify the genetic variants associated with an increased or decreased risk of developing MG in samplesfrom a Korean Multicenter MG Cohort. Materials and Methods: To determinenew genetic targets related to autoimmune MG, a whole genome-based single nucleotide polymorphisms (SNP) analysis was conducted using an AxiomTM Genome-Wide ASI 1 Array, comprising 598375 SNPs and samples from 109 MG patientsand 150 neurologically normal controls. Results: In total, 641 SNPs from five case-control associations showed p-values of less than 10-5. From regional analysis, we selected seven candidate genes (RYR3, CACNA1S, SLAMF1, SOX5, FHOD3, GABRB1, and SACS) for further analysis. Conclusion: The present study suggests that a few genetic polymorphisms, such as in RYR3, CACNA1S, and SLAMF1, might be related to autoimmune MG. Our findings also encourage furtherstudies, particularly confirmatory studies with larger samples, to validate and analyze the association between these SNPs and autoimmune MG.
참고문헌 (25)
- Meriggioli MN, "Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity", Lancet Neurol, 8, pp.475~490 (2009)
- Gregersen PK, "Genetics of autoimmune diseases disorders of immune homeostasis", Nat Rev Genet, 7, pp.917~928 (2006)
- Palmisani MT, "Myasthenia gravis and associated autoimmune diseases", Muscle Nerve, 17, pp.1234~1235 (1994)
- Garchon HJ, "Involvement of human muscle acetylcholine receptor alpha-subunit gene (CHRNA) in susceptibility to myasthenia gravis", Proc Natl Acad Sci U S A, 91, pp.4668~4672 (1994)
- Giraud M, "An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus", Nature, 448, pp.934~937 (2007)
- Vandiedonck C, "Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis", Ann Neurol, 59, pp.404~407 (2006)
- Greve B, "The autoimmunity-related polymorphism PTPN22 1858C", T is associated with anti-titin antibody-positive myasthenia gravis, 2009, pp.70, 540~542
- Chuang WY, "A CTLA4high genotype is associated with myasthenia gravis in thymoma patients", Ann Neurol, 58, pp.644~648 (2005)
- Wang XB, "CDS1 and promoter single nucleotide polymorphisms of the CTLA-4 gene in human myasthenia gravis", Genes Immun, 3, pp.46~49 (2002)
- Giraud M, "Genetic factors in autoimmune myasthenia gravis", Ann N Y Acad Sci, 1132, pp.180~192 (2008)
- Van Steen K, "Genomic screening and replication using the same data set in family-based association testing", Nat Genet, 37, pp.683~691 (2005)
- Conti-Fine BM, "Myasthenia gravis: past, present, and future", J Clin Invest, 116, pp.2843~2854 (2006)
- Bellinger AM, "Stressed out: the skeletal muscle ryanodine receptor as a target of stress", J Clin Invest, 118, pp.445~453 (2008)
- Pagala M, "Mechanisms of fatigue in normal intercostal muscle and muscle from patients with myasthenia gravis", Muscle Nerve, 16, pp.911~921 (1993)
- Takeshima H, "Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene", Nature, 369, pp.556~559 (1994)
- Chan AY, "The role of SAP and the SLAM family in autoimmunity", Curr Opin Immunol, 18, pp.656~664 (2006)
- Cocks BG, "A novel receptor involved in T-cell activation", Nature, 376, pp.260~263 (1995)
- Gregersen PK, "Risk for myasthenia gravis maps to a (151) Pro→Ala change in TNIP1 and to human leukocyte antigen-B*08", Ann Neurol, 72, pp.927~935 (2012)
- Klein RJ, "Complement factor H polymorphism in age-related macular degeneration", Science, 308, pp.385~389 (2005)
- Maraganore DM, "High-resolution whole-genome association study of Parkinson disease", Am J Hum Genet, 77, pp.685~693 (2005)
- Fung HC, "Genome-wide genotyping in Parkinson’s disease and neurologically normal controls: first stage analysis and public release of data", Lancet Neurol, 5, pp.911~916 (2006)
- Elbaz A, "Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson’s disease: a large-scale international study", Lancet Neurol, 5, pp.917~923 (2006)
- Farrer MJ, "Genomewide association, Parkinson disease, and PARK10", Am J Hum Genet, 78, pp.1084~1088 (2006)
- Goris A, "No evidence for association with Parkinson disease for 13 single-nucleotide polymorphisms identified by whole-genome association screening", Am J Hum Genet, 78, pp.1088~1090 (2006)
- Li Y, "A case-control association study of the 12 single-nucleotide polymorphisms implicated in Parkinson disease by a recent genome scan", Am J Hum Genet, 78, pp.1090~1092 (2006)