SNP 668C (−44) alters a NF-κB1 putative binding site in non-coding strand of human β-defensin 1 (DEFB1) and is associated with lepromatous leprosy

Leprosy is an infectious disease caused by Mycobacterium leprae. The peptide human β-defensin 1 is an antimicrobial effector of innate epithelial immunity. A study was done on the association of three single nucleotide polymorphisms (SNPs) in the β-defensin 1 gene (DEFB1) – 668 C/G (−44 C/G or rs1800972; in 5′ UTR), 692 A/G (−20 A/G or rs11362; in 5′ UTR) and A1836G (rs1800971; in 3′ UTR) – with leprosy susceptibility per se and clinical leprosy variants. The SNPs were genotyped by real-time polymerase chain reaction (rt-PCR) and PCR-restriction fragment length polymorphisms. Subjects were of Mexican mestizo ethnicity from Sinaloa state, México. Analysis was done on borderline leprosy, lepromatous leprosy (L-lep) and indeterminate leprosy subgroups compared with healthy controls. Results: The genotypes associated with L-lep and no other leprosy subgroup after Bonferroni correction were those that contain 668C in a dominant model (OR = 3.06, 95% CI 1.47–6.4, p = 0.024). Estimated haplotype CGA is over-represented in L-lep (p = 0.009; OR = 2.25, 1.23–4.03). Five NF-κB1 putative binding sites (NPBSs) were identified with JASPAR software in non-coding strand spanning the 5′ UTR and intron 1 of DEFB1, including one which is altered when SNP 668C is present. SNP 668C probably abrogates NF-κB-dependent DEFB1 upregulation leading to L-lep variant.