Association of Interleukin-1β-31C/T, -511T/C and -3954C/T Single Nucleotide Polymorphism and Their Blood Plasma Level in Acquired Aplastic Anemia

Abstract

Aplastic anemia (AA) is an immune-mediated disorder in which hematopoietic stem and progenitor cells are targeted by a number of cellular and molecular pathways. This case control study aims to investigate the association of interleukin-1beta (IL-1β) gene polymorphisms, (IL-1β-31, IL-1β-511 and IL-1β-3954) and their plasma levels with acquired AA. Genotyping was done by Restricted Fragment Length Polymorphism (PCR-RFLP) method and IL-1β plasma levels were evaluated in peripheral blood using ELISA. Increased level of IL-1β was reported to be significant in cases as compared to controls. The susceptibility of developing AA was higher in the cases for IL-1β-3954 genotype. IL-1β-511 genotype showed significant association with the severity groups of AA. No significant association was noticed in responder versus non-responder group. Plasma level of IL-1β gene was found to be significantly higher in severe and very-severe group of AA versus control group. Our findings suggest that IL-1β gene and its genotypes might be involved in the pathophysiology of AA and play a central role in the etiopathogenesis of AA.

Keywords: Aplastic anemia; ELISA; IL-1β-31; IL-1β-3954; IL-1β-511; Interleukin; PCR–RFLP; Polymorphism.

Fig. 1

a IL-1β-31T/C polymorphism; CC: wild homozygous (239 bp), TC: heterozygous (239 bp, 137 bp and 102 bp), TT: mutant (137 bp and 102 bp) MWL, molecular weight ladder (100 bp ladder). b IL-1β-511 C/T polymorphism; TT: wild homozygous (305 bp), CT: heterozygous (305 bp, 190 bp and 115 bp), CC: mutant (190 bp and 115 bp) MWL, molecular weight ladder (100 bp ladder). c IL-1β+3954 C/T polymorphism; CC: wild homozygous (152 bp), CT: heterozygous (152 bp, 88 bp and 64 bp), TT: mutant (88 bp and 64 bp) MWL, molecular weight ladder (50 bp ladder)

Fig. 2

Box plot showing blood plasma levels of IL-1β in healthy controls and AA patients. The box includes observations from the 25th to 75th percentile, and the horizontal line within the box represents the median value. The upper and lower lines outside the box represent the highest and lowest values of NSAA, SAA and VSAA respectively. Significant increase in IL-1β concentration were observed in SAA and VSAA patients with respect to contol