Variants in the 5q31 cytokine gene cluster are associated with psoriasis.
A multitiered genetic association study of 25 215 single-nucleotide polymorphisms (SNPs) in three case-control sample sets (1446 patients and 1432 controls) identified three IL13-linked SNPs (rs1800925, rs20541 and rs848) associated with psoriasis. Although the susceptibility effects at these SNPs were modest (joint allelic odds ratios (ORs): 0.76 to 0.78; P(comb): 1.3E-03 to 2.50E-04), the association patterns were consistent across the sample sets, with the minor alleles being protective. Haplotype analyses identified one common, susceptible haplotype CCG (joint allelic OR=1.27; P(comb)=1.88E-04) and a less common, protective haplotype TTT (joint allelic OR=0.74; P(comb)=7.05E-04). In combination with the other known genetic risk factors, HLA-C, IL12B and IL23R, the variants reported here generate an 11-fold psoriasis-risk differential. Residing in the 5q31 cytokine gene cluster, IL13 encodes an important T-cell-derived cytokine that regulates cell-mediated immunity. These results provide the foundation for additional studies required to fully dissect the associations within this cytokine-rich genomic region, as polymorphisms in closely linked candidate genes, such as IRF1, IL5 or IL4, may be driving these results through linkage disequilibrium.
Chang
M
M
Celera, Alameda, CA 94502, USA.
Li
Y
Y
Yan
C
C
Callis-Duffin
K P
KP
Matsunami
N
N
Garcia
V E
VE
Cargill
M
M
Civello
D
D
Bui
N
N
Catanese
J J
JJ
Leppert
M F
MF
Krueger
G G
GG
Begovich
A B
AB
Schrodi
S J
SJ
D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5 / Q000276:immunology*; D016207:Cytokines / Q000235:genetics*; D014644:Genetic Variation / Q000276:immunology*; D006239:Haplotypes / Q000276:immunology; D006801:Humans; D005810:Multigene Family / Q000235:genetics*; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology
D016207:Cytokines