Il-18 Overproduction Associated with NLRP1 Single Nucleotide Polymorphisms Linked to Risk for Vitiligo

Abstract

Laura J. Westhoff, Savannah J. Hughes, Erin Gill, Trent Walker, Abraham Quaye, Bradford Berges, Brian D. Poole

Background The NLRP1gene is central to the NLR inflammasome. Variants to the NLRP1 gene are associated with vitiligo and other autoimmune diseases. We examined the effects of two single nucleotide polymorphisms (SNP) son cytokine levels and NLRP1 gene expression in 50 human volunteers.

Methods NLRP1 was genotyped at SNPs rs2670660 and rs12150220, and participants who were homozygous at one or more SNP were analyzed. Plasma IL-18 and IL-1β levels were quantified using ELISA. NLRP1 gene expression was measured using real-time PCR.

Results Participants with the risk genotype had significantly higher levels of plasma IL-18 than participants with protective genotype (0.439 ng/µL compared to 0.152 ng/µL, p = 0.024). Genotypes rs2670660 and rs12150220 were strongly linked in this population (p = 2.33 x 10-13).

Conclusions Increased production of IL-18, suggests that at least one of the AA variants of rs2670660 or rs12150220 increases NLRP1 activity. rs2670660 and rs12150220 are strongly linked.

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