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Pharmacogenomics. 2012 Jan;13(1):43-53. doi: 10.2217/pgs.11.136. Epub 2011 Nov 23.

Allelic combinations of immune-response genes associated with glatiramer acetate treatment response in Russian multiple sclerosis patients.

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  • 1Russian State Medical University, Moscow, Russia. kateritsa@gmail.com

Abstract

BACKGROUND:

Glatiramer acetate (GA) is widely used as a first-line disease-modifying treatment for multiple sclerosis (MS). However, a significant proportion of MS patient appears to experience modest benefit from GA-treatment. Genetic variants affecting the clinical response to GA are believed to be relevant as biomarkers of GA-treatment efficiency.

PATIENTS & METHODS:

Nine polymorphisms in candidate genes were analyzed as possible determinants of GA response in 285 Russian MS patients. Special attention was given to identification of response-associated allelic combinations by means of the APSampler algorithm.

RESULTS:

No significant associations were found for individual polymorphisms. Alleles DRB1*15, TGFB1*T, CCR5*d and IFNAR1*G were the components of the combinations, of which carriage was significantly higher in nonresponders than in responders. Carriers of the most significant combinations: DRB1*15 + TGFB1*T + CCR5*d + IFNAR1*G and DRB1*15 + TGFB1*T + CCR5*d (permutation p-values: 0.0056 and 0.013, respectively) had a 14 to 15-times increased risk of ineffective response to GA therapy.

DISCUSSION:

The results suggest that the influence of immune-response genes on GA-induced response has a polygenic nature. The data are interpreted as evidence of additive and epistatic influences of the genes on GA efficiency for MS treatment.

[PubMed - indexed for MEDLINE]
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