Skip to main content

Table 2 Association analysis of genome-wide SNP data in patients with extreme-phenotypes of Copaxone-response

From: A pharmacogenetic signature of high response to Copaxone in late-phase clinical-trial cohorts of multiple sclerosis

Analysis steps and inclusion thresholds

Selected SNPs

Copaxone-treated patients

GALA DB

FORTE DB

Gene

SNP rsID

Odds ratio

P value

Odds ratio

P value

Step 1. Replicated variants from 35 prioritized candidate variants. Inclusion threshold: p value <0.05 GALA, p value <0.05 FORTE

HLA-DRB1*1501

rs3135391

0.66

0.040

0.64

0.0499

Step 2. Priority list of 4012 variants in 30 genes. Inclusion threshold: p value <0.05 GALA, p value <0.05 FORTE

HLA-DQB2/DOB

rs28724893

0.53

0.00060

0.46

0.00037

HLA-DOB/TAP2

rs1894408

1.72

0.0030

1.82

0.0093

MBP

rs1789084

0.70

0.036

0.57

0.01

Step 3. Broad genome-wide analysis. Inclusion threshold: p value <0.01 GALA, p value <0.05 FORTE

PTPRT

rs117602254

0.21

0.0037

0.28

0.016

ALOX5AP

rs10162089

1.56

0.0078

1.58

0.032

MAGI2

rs16886004

2.15

0.0023

5.56

3.3E-05

ZAK(CDCA7)

rs139890339

0.05

3.4E-05

0.14

0.011

SLC5A4(RFPL3)

rs73166319

*

0.0060

*

0.015

Step 4. Secondary genome-wide screen in patients with highest Copaxone response (relapse-free with no new T2 lesions). Inclusion threshold: p value <0.01 GALA, p value <0.05 FORTE

UVRAG

rs80191572

0.20

0.0024

0.12

3.4E-05

SLC1A4

rs759458

3.31

4.4E-05

1.86

0.049

  1. The 35 prioritized candidate variants and the 30 genes analyzed in steps 1 and 2, respectively, are presented in Additional file 2. SNPs selected at each analysis step met the indicated threshold of significance in the SNP-by-SNP logistic regression models built separately in the GALA DB and the FORTE DB cohorts. These models estimated the odds ratios of high versus low response. The SNPs that were selected at each step were not associated with the extreme phenotype of response in patients treated with placebo. *Odds ratios were not informative since the rare allelic variant of SLC5A4(RFPL3) was only present in high responders of Copaxone treatment and not in low responders. DB double-blind phase, MAF minimum allelic frequency