Analysis of −631 and −475 interleukin-2 promoter single nucleotide polymorphisms in multiple sclerosis

Abstract Background: Multiple sclerosis (MS) is a complex incurable neurodegenerative disease featuring demyelination of neurons, resulting in impairment of neuron impulses. Recently, an association of two single nucleotide polymorphisms (SNP) (rs2104286 and rs12722489) in interleukin 2 receptor subunit alpha (IL2RA) gene was found to be a risk factor of MS in white European population. Therefore, we performed a study to investigate the contribution of these two intronic variations in Iranian patients with MS. Methods: We determined the genotypes of rs2104286 and rs12722489 in patients with MS (n = 100) and in the control group (n = 111). The SNPs were genotyped using tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) for both of SNPs. Statistical analysis was performed by SPSS software. Also, odds ratios (ORs) and 95% confidence interval (CI) were calculated. Results: Logistic regression revealed that various genotypes of rs12722489, regarding sex-adjusted effect, yielded meaningful association with MS risk in Iranian patients (OR = 2.67, 95% CI: 1.03-6.90). However, no association was obtained for rs2104286 and rs12722489 with MS. Conclusion: The results confirmed partially the reports in white European population performed recently. However, further investigation in larger scale is necessary to validate our study.

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Analysis of multiple candidate genes in association with phenotypes of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458510364633 ◽

2010 ◽

Vol 16 (6) ◽

pp. 652-659 ◽

Cited By ~ 13

Author(s):

Madeleine H Sombekke ◽

David Arteta ◽

Mark A van de Wiel ◽

J Bart A Crusius ◽

Diego Tejedor ◽

...

Keyword(s):

Multiple Sclerosis ◽

Single Nucleotide Polymorphisms ◽

Disease Severity ◽

Clinical Data ◽

Severity Score ◽

Interleukin 2 ◽

Dna Chip ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Clinical Variables

Multiple sclerosis is a heterogeneous neurological disease with varying degrees of severity. The common hypothesis is that susceptibility to multiple sclerosis and its phenotype are caused by a combination of environmental and genetic factors. The genetic part exerts its effect through several genes, each having modest effects. We evaluated whether disease severity could be predicted by a model based on clinical data and data from a DNA chip. The DNA chip was designed containing several single nucleotide polymorphisms in 44 genes, previously described to be associated with multiple sclerosis. A total of 605 patients with multiple sclerosis were included in this analysis, using gender, onset type and age at onset as clinical covariates. We correlated 80 single nucleotide polymorphisms to the degree of disease severity using the following three outcome measures: linear Multiple Sclerosis Severity Score, dichotomous Multiple Sclerosis Severity Score (using a cut-off point of 2.5) and time to reach Expanded Disability Status Scale score 6. Sixty-nine single nucleotide polymorphisms were included in the analysis. No individual single nucleotide polymorphism showed a significant association; however, a combination of single nucleotide polymorphisms significantly improved the prediction of disease severity in addition to the clinical variables. In all three models the Interleukin 2 gene was included, confirming a previously reported modest effect on disease severity. The highest power was obtained using the dichotomized Multiple Sclerosis Severity Score as outcome. Several single nucleotide polymorphisms showed their added predictive value over the clinical data in the predictive models. These results support our hypothesis that disease severity is determined by clinical variables and genetic influences (through several genes with small effects) in concert.

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