Sex specifically associated promoter polymorphism in multiple sclerosis affects interleukin 4 expression levels

Abstract

The interleukin 4 promoter polymorphism À589 C/T (rs2243250) was genotyped in 869 multiple sclerosis (MS) patients and 595 healthy blood donors. Sex-specific MS association was evident whereas two flanking polymorphisms showed insignificant P values. In dual luciferase assays of cultured Jurkat cells the cloned promoter comprising the À589 T allele leads to higher expression as compared to the respective construct with the C allele. Together these findings may be discussed functionally as contributing to the genetic predisposition and to the pathogenesis in MS.

Relationship between the IL‐4 gene promoter ‐590C/T (rs2243250) polymorphism and susceptibility to autoimmune diseases: a meta‐analysis

“…Among these, six studies were excluded (two study for lacking genotype data of the IL‐4 ‐590 C/T polymorphism and four for HWE disequilibrium were observed in the control group) . Therefore, 24 studies were finally included in the meta‐analysis, and in total these contained 6001 patients and 6788 controls which encompassed RA ( n = 6), SLE ( n = 4), MS ( n = 2), T1D ( n = 4), and GD ( n = 8) . The characteristic of the included studies is summarized in Table .…”

“…Recently, these polymorphisms have attracted widespread attention, especially the IL‐4 gene promoter ‐590C/T (rs2243250) polymorphism. A number of case–control studies have been performed to investigate the association between this polymorphism and the susceptibility to autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), type 1 diabetes (T1D) and Graves' disease (GD) . However, the available results remain inconsistent.…”

Association of STR polymorphisms in CMA1 and IL-4 with asthma and atopy: The SAPALDIA Cohort

“…Such a congruency in the phenotypic expression between the two highly linked polymorphisms would argue that one of the polymorphic loci would be functional or that both are in linkage with another functional variant. There is indication that the IL-4 T-589 allele is associated with higher binding of transcription factors [51] and increased transcription compared with the C-589 allele [52]; however, whether this leads to an increased transcription in vivo is currently not known.…”

Polymorphic variants of the immune response genes as risk factors for primary progressive multiple sclerosis

“…Ключевая роль IL4 в регуляции воспалительных процессов объясняет вовлечение этого цитокина в патогенез как экспериментального аутоиммунного энцефаломиелита, так и РС [15,17,36,39]. Поскольку в экспериментах in vitro показано, что носительство генотипа С/C гена IL4 ведет к снижению уровня продукции IL4 в клеточной линии Т-лимфоцитов человека [24], полученная ассоциация может быть следствием пониженного уровня экспрессии гена IL4 у носителей этого генотипа, что, вероятно, способствует активации аутоиммунных воспалительных реакций при ППРС.…”