The interleukin-1 cluster gene region is associated with multiple sclerosis in an Italian Caucasian population

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Abstract

Background: Polymorphisms of the interleukin-1 (IL-1) gene family have been proposed as potential variants for different diseases including multiple sclerosis (MS). With respect to MS, IL-1 beta (-511 C/T; rs16944), IL-1 beta (+3954 C/T; rs1143634), IL-1 alpha (-889 C/T; rs1800587), IL-1 alpha (+4845 G/T; rs17561), and the variable number of tandem repeats in intron 2 of the IL-1 receptor antagonist (IL-1RN) gene polymorphisms have been studied in different ethnic groups, leading to conflicting results. Methods: This study investigates the association between IL-1 genes and MS by means of 70 markers spanning the 1.1 Mb region where the IL-1 genes map and exploring both the linkage disequilibrium (LD) and the haplotype structure in a case-control design including 410 subjects (160 patients and 250 controls). Results: From allelic/genotypic tests, significant association was found for several polymorphisms including the IL-1 beta (-511 C/T) variant (P-adjusted = 4.5 × 10-4) and some polymorphisms around the IL-1RN gene. The 'block-step' pattern obtained from both the LD map and pairwise analysis identifies four LD regions. Region 1 showed a significant association with MS for the global test (P < 0.0001) and haplotypes containing the IL-1 beta (-511 C/T) variant still demonstrate highly significant association with disease (P-value range: 9.9 × 10-5 to 0.02). Conclusions: Our findings support the existence of a causative variant for MS within this candidate region in a representative Italian Caucasian population and, in particular, the role of the IL-1 beta (-511 C/T) variant warrants further investigation. © 2010 EFNS and PNS.

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Borzani, I., Tola, M. R., Caniatti, L., Collins, A., De Santis, G., Luiselli, D., … Scapoli, C. (2010). The interleukin-1 cluster gene region is associated with multiple sclerosis in an Italian Caucasian population. European Journal of Neurology, 17(7), 930–938. https://doi.org/10.1111/j.1468-1331.2010.02952.x

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