School of Medicine and Health Sciences Poster Presentations
SPP1 Gene Polymorphisms and Response to Glucocorticoid Treatment among Myasthenia Gravis Patients
Poster Number
261
Document Type
Poster
Publication Date
3-2016
Abstract
Oral glucocorticoids (GCs) are the primary therapy for patients with myasthenia gravis (MG). However, wide inter-individual variability exists in treatment response. A cohort of 250 MG subject treated with GCs were involved, and 12 polymorphisms in secreted phosphoprotein 1 (SPP1) gene were longitudinally evaluated for the contribution of response to the initial 3 months of GCs therapy. Improvement ≥ 3 units of Quantitative MG score (QMGS) change for patients with QMGS ＞ 16, ≥ 2 units of QMGS change for patients with QMGS between 2 to 16 or QMGS after treatment becoming zero was judged as being sensitive to GC. The gene product of SPP1, osteopontin (OPN), plasma levels were assessed among MG subjects in relationship clinical parameters including SPP1 genotype.
No differences were observed for the allele distribution between GC sensitive/insensitive groups but the rs11728697 C/T + T/T genotypes were more frequent in the GC insensitive group compared to the GC sensitive group (100% versus 64.6%), indicating an association of rs11728697*T allele with GC insensitivity (pdominant = 0.018; OR = 1.065). One risk haplotype (AGTACT) was identified (p = 0.003, OR = 5.81) in the GC insensitive group compared with GC sensitive group. Mean OPN levels were higher among MG subjects (68.3 ± 43.0 ng/ml) compared to healthy controls (50.2 ± 38.7 ng/ml; p = 0.013).
There was no association between OPN concentrations and the GC sensitive haplotypes. The genotypes and the haplotype with rs11728697*T allele in SPP1 gene were identified to be associated with insensitivity to GCs treatment and elevations in OPN plasma levels were found in the population of MG subjects. OPN may contribute to MG pathogenesis and treatment response in a select population of MG patients.
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Open Access
1
SPP1 Gene Polymorphisms and Response to Glucocorticoid Treatment among Myasthenia Gravis Patients
Oral glucocorticoids (GCs) are the primary therapy for patients with myasthenia gravis (MG). However, wide inter-individual variability exists in treatment response. A cohort of 250 MG subject treated with GCs were involved, and 12 polymorphisms in secreted phosphoprotein 1 (SPP1) gene were longitudinally evaluated for the contribution of response to the initial 3 months of GCs therapy. Improvement ≥ 3 units of Quantitative MG score (QMGS) change for patients with QMGS ＞ 16, ≥ 2 units of QMGS change for patients with QMGS between 2 to 16 or QMGS after treatment becoming zero was judged as being sensitive to GC. The gene product of SPP1, osteopontin (OPN), plasma levels were assessed among MG subjects in relationship clinical parameters including SPP1 genotype.
No differences were observed for the allele distribution between GC sensitive/insensitive groups but the rs11728697 C/T + T/T genotypes were more frequent in the GC insensitive group compared to the GC sensitive group (100% versus 64.6%), indicating an association of rs11728697*T allele with GC insensitivity (pdominant = 0.018; OR = 1.065). One risk haplotype (AGTACT) was identified (p = 0.003, OR = 5.81) in the GC insensitive group compared with GC sensitive group. Mean OPN levels were higher among MG subjects (68.3 ± 43.0 ng/ml) compared to healthy controls (50.2 ± 38.7 ng/ml; p = 0.013).
There was no association between OPN concentrations and the GC sensitive haplotypes. The genotypes and the haplotype with rs11728697*T allele in SPP1 gene were identified to be associated with insensitivity to GCs treatment and elevations in OPN plasma levels were found in the population of MG subjects. OPN may contribute to MG pathogenesis and treatment response in a select population of MG patients.
Comments
Presented at: GW Research Days 2016