SNP 668C (-44) alters a NF-kappaB1 putative binding site in non-coding strand of human beta-defensin 1 (DEFB1) and is associated with lepromatous leprosy.
Leprosy is an infectious disease caused by Mycobacterium leprae. The peptide human beta-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 beta-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-kappaB1 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-kappaB-dependent DEFB1 upregulation leading to L-lep variant.
Prado-Montes de Oca
Ernesto
E
Guadalajara University, Guadalajara, Jalisco, Mexico. eprado@ciatej.net.mx
Velarde-Félix
Jesús Salvador
JS
Ríos-Tostado
Juan José
JJ
Picos-Cárdenas
Verónica Judith
VJ
Figuera
Luis Eduardo
LE
D001483:Base Sequence; D001665:Binding Sites; D016009:Chi-Square Distribution; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015440:Leprosy, Lepromatous / Q000235:genetics* / Q000276:immunology; D015810:Linkage Disequilibrium; D008800:Mexico; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023083:beta-Defensins / Q000235:genetics*
C406407:DEFB1 protein, human; D016328:NF-kappa B; D023083:beta-Defensins