The Association of Interleukin-16 Gene Polymorphisms with IL-16 Serum Levels and Risk of Multiple Sclerosis

Abstract

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) that is immunologically mediated in genetically susceptible individuals. Interleukin-16 (IL-16), a pleiotropic cytokine, is an important regulator of T-cell activation which plays a key role in autoimmune diseases. Single-nucleotide polymorphisms (SNPs) in the IL-16 gene may lead to altered cytokine expression or biological activity, and these variations may modulate an individual's risk for MS. To test this hypothesis, we investigated association of IL-16 gene SNPs (i.e., rs4072111 C/T, rs11556218 G/T, and rs4778889 C/T) and serum IL-16 levels with risk of MS in an Iranian population. METHODS: We analyzed the three SNPs of IL-16 in 250 MS patients and 400 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The serum level of IL-16 was assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The IL-16 rs4072111C/T genotype and allele frequencies showed significantly differences between MS patients and controls (p < 0.01). Statistically significant differences were also found in allele and genotype frequencies of rs11556218 G/T between two groups (p </= 0.01). The mean serum levels of IL-16 in MS patients were significantly higher in MS patients compared to healthy controls (p </= 0.01). CONCLUSION: In summary, the present study provides the first evidence that the rs11556218T/G and rs4072111C/T polymorphisms of IL-16 gene were significantly associated with increased risk of MS. These results suggest that rs11556218T/G, rs4072111C/T, and rs4778889T/C polymorphisms of IL-16 may contribute to susceptibility to MS through increased expression of IL-16 levels.