title: Genetic analysis of interleukin-1 receptor antagonist and interleukin-1β single-nucleotide polymorphisms C-511T and C+3953T in alopecia areata: susceptibility and severity association.
abstract: The present study was aimed to explore the effect of two selected polymorphisms from interleukin-1β (IL-1β) gene [SNPs -511 and +3953] and a variable number of tandem repeat (VNTR) from interleukin-1 receptor antagonist (IL-1RN) on the susceptibility and severity of alopecia areata (AA) in Kuwaiti subjects. IL-1β SNPs C-511T, C+3953T, and IL-1RN VNTR were screened in 96 alopecia patients classified clinically, according to the disease severity as patchy (P), semiuniversalis (SU), and universalis (U), and in 100 ethnically matched healthy controls. Polymerase chain reaction followed by restriction fragment length polymorphism and direct DNA sequencing were employed for genotyping. Comparing the stratified AA cases based on severity, IL-β SNP C-511T showed a significant association (genotype and allelotype levels p = 0.03 and p = 0.028, respectively). Genotype CC was 50 % more frequent in U cases than in P or SU. When P and SU were grouped and tested against U, a significant difference was observed (genotype and allelotype levels p = 0.006 and p = 0.008, respectively). Compared to genotype CT, carriers of IL-1β -511 CC genotype showed an increased risk to develop severe AA (p = 0.004, OR = 4.14, 95 % CI = 1.61-10.69). Four alleles and genotypes (1/1, 1/3, 1/4, and 2/2) of IL-1RN VNTR were detected in AA patients while only two (1/1 and 1/3) in controls. IL-1RN VNTR showed genotype and allelotype association with AA (p = 0.05 and p = 0.025, respectively). Our results showed that IL-1β and IL-1RN VNTR are significantly associated with the susceptibility to alopecia areata. Allele C of the IL-β C-511T SNP is linked to the severe form of AA.
authors.affiliation: Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, PO Box 31470, Sulaibekhat, Kuwait, Kuwait, s.alfadhli@hsc.edu.kw.
authors.forename: Suad
authors.initials: S
authors.lastname: Alfadhli
authors.forename: Arti
authors.initials: A
authors.lastname: Nanda
mesh_terms: D000506:Alopecia Areata / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D007730:Kuwait; D008297:Male; D018598:Minisatellite Repeats; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta